dithiolh rearrament . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36ent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37nt . . . .. . . . . . .s using

Contents lists available at SciVerse ScienceDirect

Tetrahedron

Tetrahedron 68 (2012) 15e453.8.2. Carbamate synthesis using sodium cyanate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393.8.3. Carbamates synthesis using Burgess reagent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393.8.4. Carbamate synthesis through transcarbamoylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393.8.5. Carbamate synthesis using ureas and alcohols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403.8.6. Carbamate synthesis from carbonyl compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403.8.7. Carbamate synthesis from oximes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41References and notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41Biographical sketch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453.7.1. Hoffmann rearrange3.7.2. Curtius rearrangem3.7.3. Lossen rearrangeme

3.8. Miscellaneous methods . . . .3.8.1. Carbamate synthesi* Corresponding author. Fax: 91 376 2370011; e-m

0040-4020/$ e see front matter 2011 Elsevier Ltd.doi:10.1016/j.tet.2011.10.001. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38carbonyl di-imidazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383.6.2. From carbon-imido3.7. Carbamate synthesis througates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36ngement reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36Tetrahedron report number 958

Perspectives on the synthesis of organic carbamates

Devdutt Chaturvedi *

Natural Products Chemistry Division, North-East Institute of Science and Technology (CSIR), Jorhat 785006, Assam, India

a r t i c l e i n f o

Article history:Received 6 September 2011Available online 6 October 2011

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .162. Classification of carbamates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .173. Methods of preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17

3.1. Phosgenation technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173.2. Reductive carbonylation of nitroaromatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193.3. Oxidative carbonylation of amines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223.4. Using metal/non-metal carbonates/bicarbonates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223.5. Synthesis of carbamates using carbon dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3.5.1. Gaseous carbon dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233.5.2. Electrochemical carbon dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293.5.3. Supercritical carbon dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303.5.4. Organic carbonates with carbon dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

3.6. Carbamate synthesis from dithiocompounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363.6.1. Using dithiocarbamates/thiocarbamates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36journal homepage: www.elsevier .com/locate/ tetail addresses: ddchaturvedi@rrljorhat.res.in, devduttchaturvedi@gmail.com.

All rights reserved.

1. Introduction

Organic carbamates are a stable class of compounds derivedfrom the unstable carbamic acid (H2NeCOOH) by substitution ofthe amino and carboxyl moieties with various kinds of structurallydiverse alkyl/aryl, aryl/alkyl or substituted alkyl/aryl and aryl/alkylgroups, and are identied by the presence of the linkageOeCOeNHe.1,2 When the carbamate linkage is present in a cyclicsystem, this class of compounds are referred to as cyclic carba-mates.3 When the carbamate group is attached to any inorganicatom, either metallic or nonmetallic, such compounds are referredto as inorganic carbamates.4

Organic carbamates represent an important class of compoundsshowing various interesting properties. They nd wide utility inareas, such as pharmaceuticals,5 agrochemicals6 (pesticides, her-bicides, insecticides, fungicides etc.), as intermediates in organicsynthesis,7 for the protection of amino groups in peptide chemis-try,8 and as linkers in combinatorial chemistry.9 Functionalisationof amines as carbamates offers an attractive method for the gen-eration of derivatives, which may have interesting medicinal andbiological properties.10 Organic carbamates have been extensivelyused as intermediate for the synthesis of structurally diverse syn-thetic intermediates/molecules of biological signicance.11 There-fore, considerable interest has been generated in the recent past inthe development of efcient and safe methodologies for carbamateester synthesis.

Organic carbamates have frequently been employed as phar-maceuticals in the forms of drugs and prodrugs.5a,12a In recent

anti-HIV, antiestrogenic, antiprogestational, antiosteoporosis, anti-inammatory, antilarial, antitubercular, antidiabetic, antiobesity,anticonvulsant, antihelminthes, anti-alzheimer drugs and CNS andCVS active agents (Fig. 1).5c,d,14

Some of the recent molecules in which the extensive role ofincorporation of carbamates have been studied are dis-codermolide,15 camptothecin16 podophyllotoxin,17 mitomycins,18

vitamin-D3,19 geldanamycin,20 fumagillin analogues,21 butelinicacid,22 amphotericin-B,23 cephalosporins,24 doxorubicin,25 rapa-mycin,26 anisomycin,27 quiniclidine,28 phytostigmine,29 novobio-cin,30 oestradiol,31 cholesterol,32 sphingomyelin,33 vancomycin,34

marphinan,35 rifampicin,36 vulmbactin,37 pregnelone,38 himba-cine,39 iejimalides,40 rhazinilam,41 maytansine,42 calcheamycin,13c

combretastanin,43 cyclosporin,44 duocarmycins45 etc. Beside theabove mentioned molecules, several kinds of other structurallydiverse natural/synthetic molecules have also been reported in therecent years wherein carbamates play crucial role in improving thebiological activity prole than the parent molecules. Some of theimportant potential carbamates derivatives of structurally diversebiologically active anticancer,19,46 antibacterial,5e,47 antimalarial,48

antidiabetic,49 antioxidant,50 antiinamatory,51 antitubercular,52

antiprogestational,53 anti-HIV,17 anticougulant,54 antiestrogenic,55

CNS-active,28 are depicted in Figs. 2e5, respectively. Several ofnatural, semisynthetic, synthetic lead molecules bearing carbamatefunctionality have been discovered in recent past and are in thevarious phases of drug development.5,12a,13,56

Although, some of the review articles on the different aspects onthe chemistry of organic carbamates have been published but the

O

D. Chaturvedi / Tetrahedron 68 (2012) 15e4516years, several reports have indicated that the carbamate linkagepresent in the active pharmacophores of various structurally di-verse molecules increases the biological activities of semisynthetic/synthetic natural/synthetic molecules.13 Furthermore, the role ofthe carbamate linkage has been extensively studied in structurallydiverse natural/semisynthetic molecules against various diseases,such as anticancer, antibacterial, antifungal, antimalarial, antiviral,

OAcO

OH

OOH

O

O

O

NHO

O

OH

O

OH

S

N

N

O

NH2

O

N

Cl

Cl

Capravirine: anti-HIV

O NHCH3

O

Taxol analogues: anticancer drugsCarbaryl: Insecticide

Fig. 1. Biologically active drug molecreview articles dealing synthetic aspects of the carbamates wereonly published long back.1a,2aed Furthermore, till now there is norecent review published since more than 3 decades, which couldcover the synthetic aspects of the organic carbamates. Since last2e3 decades, much progress on the synthesis of organic carba-mates has been realised, employing various kinds of cheap and safealternatives, such as various forms of carbon dioxide, organic

N

N

OH3CHN

O

Physostigmine: Anti-alzheimer drug

NO

O

N

NH

O

F

Linezolid: Antibacterial drug

O

OO

O

O

O

HON

ON

O

O

N

N

N

Telithromycin: Antibacterial drugules bearing carbamate linkage.

NH

O

O

O

MeO

MeOOH

Geldanamycin

OH

H

hedrO

O

O

HN

O

O

H2N

O

O

OH

O

PPI-2458

D. Chaturvedi / Tetracarbonates and several other useful synthetic routes. Thus, keepingthe above views under considerations this review has been plannedto deal on the various synthetic aspects of organic carbamates withthe special emphasis on the recent methodologies.

2. Classication of carbamates

Carbamates can be mainly classied into two groups, namelyinorganic and organic. Depending upon the structural variations inthe attached moieties, they are further classied as shown in Fig. 6.

3. Methods of preparation

3.1. Phosgenation technique

Phosgene (1) is a potentially useful, versatile building block inorganic synthesis.57 It offers the possibility of binding two nucle-ophilic units to the same carbon atom and this two-componentsystem is particularly well suited for the combinatorial synthesisof carbonates, ureas and carbamates (Scheme 1). Phosgene is,however, extremely toxic, which limits its use. Safer substituteshave been proposed, such as 1,1,1-trichloromethylformate (di-phosgene 2),58 and bis-(1,1,1-trichloromethyl) carbonate (tri-phosgene 3),59 which have been frequently used in recent years.Depolymerisation of 3 into 1 has widely replaced phosgene by

HN

Vitamin D3 carba

O

O

O

O

MeO OMe

O

O

R

NH O

O

N

Podophyllotoxin analogues

Fig. 2. Potential anticancer carbamaON

OO NH2

O

OMe

on 68 (2012) 15e45 17triphosgene, which is relatively safer to use.60 Thus, carbamate 6synthesis has been achieved through the reaction of an amine 4with an alcohol 5 using either 1, or 2 or 3 as the source of a carbonylequivalent (Scheme 1).

Chloroformates and isocyanates are intermediates producedfrom phosgene, and have frequently been employed in the syn-thesis of organic carbamates. Chloroformates57a 7, obtainedthrough the reaction of alcohols/phenols 5 with phosgene 1, reactwith amines/substituted amines 4 (i.e., aminolysis) affording car-bamates61 6 (Scheme 2). Carbamate synthesis through the chlor-oformates route has been achieved using different reaction

OH

mate dimer

O

NH

HN O

O

NHO

CH3

Staurosporine derivatives

tes of various natural products.

Cl Cl

O

Cl O

O

C

Cl

ClCl

O O

O

C

Cl

ClCl

Cl

Cl Cl

1 2 3

X X

O

R1NH2 +

(either 1 or 2 or 3)+ R2OH

NHR1 OR2

O

4 56

Scheme 1.

O HO

N

OMe

O

O

NHO

O

HO

HO

OO

HO

N

OMe

O

O

NH R

D. Chaturvedi / Tetrahedron 68 (2012) 15e4518O

N

O

O

O

OO

O

OMe

O

Rconditions, such as the use of strong bases8a,62 (NaOH, NaHCO3,Et3N, pyridine and triphenylphosphine), metals,63 ultrasound,64

bis(trimethylsilyl)acetamide61 and in combination with azides.63

In recent years, there has been much attention focused on thesynthesis of carbamates using chloroformates as key intermediates.Thus, Pandey and co-workers have reported65 an efcient synthesisof carbamates 6 through the reaction of variety of amines 4 withchloroformates 7 using catalytic amount of a yttriaezirconiumbased Lewis acid catalyst (Scheme 3).

O

N

O

HO

O

O

OO

HO

N

OHOHN

R2

O

O

O

NHOMe

Azithrom

O

NN

SHN

O

COOH

O

OO

Carbamate conjugate of ceph

Eryth

Fig. 3. Potential antibacterial carbam

Scheme 2.

R1NH2 + ClCOOR2

yttria-zirconia basedLewis acid catalyst

rt, 5 min-6 h, 88-96%4 76

R2O NHR1

O

Scheme 3.R O

NHO

N

OH

romycin derivativesLater, Mormeneo and co-workers have reported66 a versatilemethod for the synthesis of carbamates 6 through an in situ gener-ated, polymer-supported chloroformate resin 9. Bis-(1,1,1-trichloromethyl) carbonate (BTC, triphosgene) has been used asa phosgene equivalent to afford a supported chloroformate 9, whichon sequential one-pot reaction of a variety of alcohols 5with amines4 afforded the corresponding carbamates 6 in high yields via 10(Scheme 4).

R1

ycin derivatives

O

O

O

O

O

OO

O

NHR

N O

O

XAc

N

F

alosporin with oxazolidinones

ates of various natural products.

OH BTCPyr

O Cl

O

R2OHPyr

O OCH2R2

O

R1 NH2

8 910

4

6

75-99%

5

R2O NHR1

O

Scheme 4.

OH

Antidiabetic

NO

O

S

NO

HN

OPh

Antitub

COOR

O

Antioxidant

ates

hedrRaje and co-workers have reported67 an efcient, one-pot syn-thesis of N-substituted (3-oxobutyl) carbamates 12, via tandemcondensation of primary amines 4 with methyl chloroformate 7

Fig. 4. Biologically potent carbamNN

O

O

O

NHHN

O

CF3

Cl

Antimalarial

N

O

O

F3CNH

O

O

F

ClD. Chaturvedi / Tetra(R2Me) followed by conjugate addition of the resulting carba-mates withmethyl vinyl ketone 11 in the presence of Sn4modiedzeolite Hb (Hb-SnA) at room temperature (Scheme 5).

More recently, Kim and Jung have reported68 a simple and ef-cient synthesis of carbamates 6, through reacting equimolaramounts of amines 4, chloroformates 7 and indium metal (Scheme6). Thus, carbamates of structurally diverse substituted aliphatic,aromatic and heterocyclic amines were prepared using variouskinds of chloroformates.

R1NH2 + Cl OR2

O

R2 = - CH3, -CH=CH2, Bn

7-12 h,rt,

73-91%4 7 6

In

R2O NHR1

O

Scheme 6.

Isocyanates2a,69a 13, obtained through the reaction of phosgene1 and amines 4, reacts with hydroxy compounds 5 (i.e., alcohol/

R1NH2 + ClCOOR2

O

R1NCOOR2

O

24 h, 68-75%4 7

11

12Scheme 5.phenols) affording the corresponding carbamates is the mostcommon way to synthesise carbamates (Scheme 7).70 Poly-urethanes,71a the building blocks of isocyanates, have been exten-

N

COOH

O

F

N

ercular

O

HO

H

OHO

O

F

NH

O

R

Antiinflammatory

of natural/synthetic molecules.O NNO

HO

on 68 (2012) 15e45 19sively used in industry. Some of the 12 million tonnes ofpolyurethanes are made annually from the reaction between gly-cols and diisocyanates, and there are currently many papers andpatents on ways to catalyse and control these reactions.71b Thesynthesis of carbamates starting from isocyanates could be ach-ieved through the use of strong bases,72 and metal halides73 etc.Carbamates could be converted into isocyanates by thermal de-composition at higher temperatures using different reaction con-ditions, such as use of metal catalysts,74 chlorocatecholborane/boron halides with triethylamine,75 silanes,76 chlorosilanes,77

dichlorosilanes,78 Mitsunobu reaction conditions,79 montmoril-lonite K-10,80 Bi2O3,81 and very recently basic metal oxide nano-particles82 etc.

Cl Cl

O

+ R1NH2 R1-N=C=O

13

+ R2OH

- R2OH R2O NHR1

O

14

6

5

Scheme 7.

3.2. Reductive carbonylation of nitroaromatics

The reductive carbonylation of aromatic nitrocompounds 14 tothe corresponding carbamates is an interesting approach towardsthe synthesis of carbamates 15 (Scheme 8).83 The carbonylationreaction of nitroaromatics is exothermic and is catalysed by palla-dium, ruthenium, and, to a lesser extent, rhodium. In addition,platinum,84 iridium85 and iron,86 have been reported to be active inthis reaction.

NO

O

Et EtHN

Cl

Cl

O

O

MeO OMe

OH

NH O

O

ON

NH

O

O

Anti-HIV

O

hedron 68 (2012) 15e45CNS-Active

NH

NH

OOAntiprogestational

O NH

O

R2

R1

O

OD. Chaturvedi / Tetra20Scheme 8.

For a reductive carbonylation of aromatic nitrocompounds car-ried out in alcohols, it might generally be considered that the car-bamates16 are formed by the reaction of aromatic isocyanatesArNCO, with an alcohol ReOH, outside the coordination sphere ofthe metal.87 However, Cenini has found in the case of Ru3(CO)12with NEt4Cl as a co-catalyst that the alcohol participates in thecatalytic cycle, since, when it was absent, practically no isocyanatewas obtained (Scheme 9).

Several reports have been published by Gladfelter and Ceninigiving more insight into the mechanism of the catalytic cycle of therhodium and ruthenium catalysts. Gladfelter88 has proposed

N

N

O O

Anticoagulant

Fig. 5. Biologically potent carbamate

LnM=N-ArCO, R'OH

LnMNH-Ar

COOR'

COAr-HN OR'

O

+ LnMC=O

16

Scheme 9.ONHamechanismusingRu(dppe)(CO)317dppebis(diphenylphosphino)-ethane as a catalyst through the involvement of intermediates 18e22,in which an aromatic amine 4 is suggested as a linker intermediate(Scheme 10).

HOAntiestrogenic

s of natural/synthetic molecules.

Ru COCO

P.Ph2Ph2.P

OC17

+ ArNO2

Ru

CO

P.Ph2Ph2.P

OC

O

NAr

18

Ru

CO

P.Ph2Ph2.P

OC

ONAr

19

Ru

CO

P.Ph2Ph2.P

OC

20

O

+ CO

-ArNH2-CO2

Ru

CO

P.Ph2Ph2.P

OC

COOMe

COOMe

Ru

CO

P.Ph2Ph2.P

OCNAr

O

O

OMe

H

-MeOH21

=OH

OMe

22

ArN=C=O

Ar-CO-NH.Ar

ArNH2

-CO2

+ArNH2

16

R1NH24

Ar-NH OR'

O

Scheme 10.

tes

cinagrO

Saturated Unsaturated

ted

A

lic

hedron 68 (2012) 15e45 21Metal Non metal

Aliphatic Aliphatic-aromatic

Simple Substitu

Simple

Linear Branched Alicyc

Symmetrical Unsymmetrical

Symmetrical UnsymmetricalCarbama

cinagronI

D. Chaturvedi / TetraVery similar results were obtained by Cenini using [(PPh3)2N][Rh(CO)4] 23 as a catalyst through the involvement of intermediates24e27(Scheme 11).4d,89

[(Rh(CO)4]Ar-NO2

O N

ORh

O

Ar

O=C

O=C

N

ORh

Ar

O=C

O=C

+ CO

N

CO2Rh

Ar

O=C

O=C

COOMeRh

O=C

O=C COOMe

+ 2CO & 2MeOH

+ CO, ArNH223

24

25 26

27

[(PPh3)2N]

Scheme 11.

Most previously reported catalytic systems for the reductivecarbonylation of aromatic nitrocompounds have usually employedcorrosive Lewis acids and/or a base,90 such as pyridine or triethyl-amine in excess amounts, e.g., supported palladium is inactive inthe absence of a Lewis acid, even in the presence of an excess ofpyridine, whereas PdCl2 exhibits good activity in the absence ofLewis acids, but requires an excess of base. Palladium(II) complexes

elpmiS

Fig. 6. ClassicationSymmetrical Unsymmetrical

Aromatic Others

ctivated Cyclic

Simple Functional

Thio Imido Ortho Pyro

Linear-alicyclicof the type [Pd(Py)2Cl2] can catalyse the reaction at a low Py/Pdratio, but the method requires promotors, such as FeCl3 or MoCl5and aprotic solvents, such as chlorobenzene.91 On the other hand,reductive carbonylation of aromatic nitrocompounds could becatalysed by palladium anchored to montmorillonite,92 supportedPd-1,10-phenanthroline complexes in the presence of a Brnstedacid,93 Pd complexes with 1,10-phenanthroline derivatives and Pdheteropolyanions.94 In addition, ruthenium carbonyl complexes,such as Ru3(CO)12 or Ru(CO)3(PPh3)2 are efcient homogeneouscatalysts in the reductive carbonylation of aromatic nitro-compounds to carbamates, if additives, such as alkylammoniumsalts,95 chelating ligands,96 or anilines97 are used. Palladium98 hasoften been applied as a catalyst in homogeneous and heteroge-neous systems. Rhodium2d catalysts have also been applied lessoften to the reductive carbonylation of nitrobenzene than ruthe-nium and palladium catalysts.

Chandrasekhar and co-workers have reported64 an efcientprotocol for the synthesis of carbamates 15 through the reductivecarbonylation of aromatic nitrocompounds 14 with either (Boc)2O28, or ClCOOEt using a Sn/NH4Cl system under ultrasound radiation(Scheme 12).

detutitsbuS

of carbamates.

R

NO2

Sn/NH4Cl

79-93% R

HN OR'

O

14 15

+ ClCOOEt or (Boc)2O MeOH, ultrasound28

R' = Et, tert.Butyl

Scheme 12.

efcient protocol for the synthesis of N-aryl N-hydroxy carbamates29, through a one-pot procedure involving zinc-mediated reductionof nitroarenes 14 in the presence of chloroformates 7 (Scheme 13).

NO2

Zn/NH4Cl

N OR2

O

HO

106

reported by Zhang and co-workers (Scheme 22).112

3.4. Using metal/non-metal carbonates/bicarbonates

Carbonates and bicarbonates have been effectively employed forproviding a carbonyl functionality for the preparation of carba-

Scheme 17.

hedrMizuno and co-workers have reported the synthesis of 2-oxazolidinone derivatives in which 2-aminoethanols 30 were eas-ily subjected to thiocarboxylation with CO promoted by elementalsulfur followed by oxidative cyclisation with molecular oxygen toafford the corresponding 2-oxazolidinones 31 in good yields undermild reaction conditions (Scheme 16).

Wan and co-workers have reported107 an efcient synthesis ofcarbamate esters 6, through the oxidative carbonylation of amines

Scheme 16.R1NH2 + CO + HOR2 + 1/2 O2metal cat.

R2O NHR1

O

4 5 6Scheme 14.

The use of iodine promoted by a Pd catalyst,104 or a gold complexwith triphenylphosphine105 has also been reported in the synthesisof carbamates (Scheme 15).

R1NH2 + CO + HOR2 + I2Pd cat.

R2O NHR1

O

4 56

Scheme 15.3.3. Oxidative carbonylation of amines

Carbamates 6 have been prepared in good-to-excellent yieldsthrough the reaction of amines 4, alcohols 5, carbon monoxide andoxygen in the presence of novel metal catalysts. The metallic cat-alysts used during the oxidative carbonylations are palladium,100

platinum and alkali metal halides,101 or CO, Cu and Rh (Scheme14).102 Pd and Cu halides have also been employed as catalystsduring the oxidative carbonylation process.103RNaOMe, 89-97%

R14 29

+ ClCOOR27

Scheme 13.More recently, Tomkinson and co-workers have reported99 an

D. Chaturvedi / Tetra224 with alcohols 5 using a PVP-polymer-supported palladium/manganese bimetallic catalyst (Scheme 17).R1NH2 + CO + R2OHO2 R1NHCOOR2

Co(salen)in zeolite4 5 6Scheme 21.

More recently, the synthesis of N-phenyl carbamates 6 throughthe selenium-catalysed oxidative carbonylation of aniline 4 andalcohols 5 in the presence of carbon monoxide and oxygen wasScheme 20.

Recently, Mei and co-workers have reported111 the synthesis ofmethyl N-phenyl carbamates 6 through the oxidative carbonylationof aniline 4, using a series of recoverable Co(salen) complexes inzeolite-Y as catalysts, where the Co(salen) complexes were suc-cessfully encapsulated in zeolite-Y by a exible-ligand method(Scheme 21). They studied the catalytic activity of various kinds ofCo(salen) complexes over zeolite-based catalysts.Scheme 19.

Later, Shi and co-workers have also reported110 a high-yielding efcient carbonylation of amines 4 with variety of al-cohols 5 using a palladium complex-ionic liquid to afford car-bamates 6. The desired products could be precipitated by addingwater into the resulting reaction mixture and the catalysts sys-tem could be reused with only a slight loss of catalytic activity(Scheme 20).

R1NH2 + CO + R2OHO2 R1NHCOOR2

Pd(phen)Cl2-[Bmim]BF44 5 6R1NH2 + CO + R2OHO2 R1NHCOOR2PdCl2-ZrO2-SO44 5 6

Scheme 18.

Shi and co-workers have reported109 an efcient and cleansynthesis of carbamates 6 through oxidative carbonylation of aro-matic amines 4 using polymer-immobilised gold catalysts (Scheme19).

R1NH2 + CO + R2OHO2 R1NHCOOR2Au/Polymer4 5 6Later, Shi and co-workers have reported108 a novel synthesis ofcarbamates 6 through the oxidative carbonylation of amines 4withalcohols 5 using a PdCl2/ZrO2eSO42catalyst system at 170 C(Scheme 18).R1-NH2 + CO + R2OHO2

PVP-PdCl2-MXnR1-NHCOOR2

4 5 6

on 68 (2012) 15e45mates. A variety of metal carbonates, such as potassium carbonate(K2CO3), sodium carbonate (Na2CO3), and caesium carbonate

R-NH2 + CO2 R-NH-COOH36 37

2 2 2 R2N C O OEt

t3N,

me

hedrtertiary amines 33 during the one-pot, efcient synthesis of car-bamates 6 from the corresponding alkyl halides 32 and amines 4was rst investigated by Butcher115 (Scheme 25). He found thatCs2CO3 was much better than K2CO3 in providing better yields ofcarbamates from the corresponding alkyl halides and amines.

R1NH

R2

+ R3XCs2CO3

R1N

R2

COR3

O

+

R1NR3

R24

32 6 3344-96% 0-19%

Scheme 25.bamates.114 Moreover, this method was not efcient for the pro-duction of only O-alkylated carbamates 6, due to the formation ofN-alkylated amines 33 (Scheme 24).

R1NH

R2

+ R3XNa2CO3 R1

N

R2

COR3

O

+

R1NR3

R24

32 6 33Scheme 24.

The role of Cs2CO3 in minimising the synthesis of N-alkylatedcatalytic systems. The synthesis of carbamates 6 through the re-action of variety of secondary amines 4 with structurally diversealkyl halides 32 was achieved using K2CO3/tetra-n-butylammo-nium hydrogen sulfate (Scheme 23).113 This method produces car-bamates 6 as the major product along with a minor amount of N-alkylated amines 33.

R1NH

R2

+ R3X(n-Bu)NHSO4

K2CO3

R1N

R2

COR3

O

+

R1N.R3

R24

32 6 33Scheme 23.

Sodium carbonate has also been used in the synthesis of car-(Cs2CO3) have been used alone and in combination with different

NH2 + ROH + CO + 1/2 O2E5

4

Sche

D. Chaturvedi / TetraSeveral bicarbonates have been used for the synthesis of car-bamates. Of these, sodium bicarbonate (NaHCO3) has found usein peptide chemistry.116 Inesi and co-workers have reported117

the synthesis of linear carbamates 6, starting from the corre-sponding primary and secondary amines 4 and alkyl halides 32using tetra-ethylammonium hydrogen carbonate (Et4NHCO3) asthe carbonyl source (Scheme 26). The yields of carbamates wereaffected by the nature of the alkyl halides used. They havefurther extended the methodology to the synthesis of cycliccarbamates 35 starting from the corresponding haloamines 34using Et4NHCO3.4Scheme 27.

Yoshida and co-workers have reported122 the synthesis of car-bamates 6, starting from CO2 36, amines 4 and unsaturated ethers38 (Scheme 28). This method limits the carbamate synthesis tothose produced from secondary aliphatic amines. Moreover, it re-quired longer reaction times (w70e80 h) and afforded low yields(3e12%).

R NH + CO + CH =CH-O-Et

O~70-80 hScheme 26.

3.5. Synthesis of carbamates using carbon dioxide

Carbon dioxide has been frequently used, in various conditionsand forms, as a cheap and safe alternative for the synthesis ofcarbamates,118 carbonates,119 and for several other interesting or-ganic transformations.120 Carbamate synthesis using various formsof carbon dioxide, such as gaseous, electrochemical, and super-critical has been achieved in recent years employing a diversity ofreagents and catalytic systems.

3.5.1. Gaseous carbon dioxide. Carbon dioxide 36 has a low re-activity,121 e.g., with amines 4 it forms unstable carbamic acids37, which revert to their corresponding starting materials(Scheme 27).R1NH

R2

+ R3.XEt4NHCO3

R1

N

R2

COR3

O

Br-CH2(CH2)n-NH2.HBrO

HN

O

( )n

4

Et4NHCO3

63253-98%

3435

n = 1, 56%n = 2, 42%

6

22.6 h, up to 85%

SeNH OR

O

on 68 (2012) 15e45 234 36 38 63-12%

Scheme 28.

Later, Yoshida and co-workers have also reported123 thesynthesis of carbamates 6 through a one-pot reaction of amines4 with alkyl halides 32 using gaseous CO2 (Scheme 29). Thecarbamates obtained in this method are also limited to thoseproduced from primary and secondary aliphatic amines, andrequire longer reaction times (w45 h), and afford low (6e25%)yields.

Later, Ishii and co-workers have reported124 the synthesis ofcarbamates 6 through a one-pot reaction of primary or secondaryaliphatic amines 4 with ortho esters 39using gaseous CO2 (Scheme

and gaseous CO2 (Scheme 32), but this method was not satisfactory,due to its longer reaction time (w3e4 days), and it afforded lowyields (5e20%).

+ CO2 O+OH

O C N

O

R1

R2

Ti(NMe2)443

4140

~ 3-4 days

5-20%

R1 & R2 = Me

Similarly, chloromethyl oxirane 44 or phenyl oxirane 48 on re-action with CO2 and aliphatic amines in methanol gave variouskinds of substituted carbamates127 46, 47, 50, 51 in 2e17% yieldsthrough the involvement of intermediates 45, and 49, respectively(Scheme 33).

Later, better yields have been reported by Yoshida and co-workers through the reaction of various epoxides 52 with a varietyof amines 4 using gaseous CO2 36 (Scheme 34).128 However, thismethod leads to isomeric mixtures.

Scheme 36.

when 2-methoxy 3,3-dimethyl-2-phenyloxirane 56 or a-bromo-iso-butyrophenone 55 was reacted with CO2 and aliphatic a,u-di-amines 58 (Scheme 37).

R1NH

R2

+ R3 X + CO2R1

N

R2

COR3

O

4 32 36 6

~ 45 h6-25%

Scheme 29.

O

R1 R2CO2+ NH

R'

R''+

R1

HOO

O

NR'

R''R2

R1

HO NR'

R''R2+

52 36 4

D. Chaturvedi / Tetrahedron 68 (2012) 15e4524Scheme 32.the corresponding 1,2-epoxides 40 through the reaction of primaryand secondary aliphatic amines using gaseous CO2 (Scheme 31).About half of the epoxide is lost, however, due to the accompanyingnucleophilic ring opening by the amine to afford the N-alkylatedproducts 42.

NH

R1

R2+ CO2 O+

22-24 h

42-52%

OH

O C N

O

R1

R2

OH

N

R1

R2

+

4 36 40 41 42

Scheme 31.

The mono-carbamates 41 could also be obtained,126 startingfrom epoxide 40, using tetrakis(dimethylamino)titanium(IV) 4330). This method requires long reaction times and afforded carba-mates in low yields.

Mono-carbamates of 1,2-diols 41 have been synthesised125 from

R1NH

R2+ CO2

R1N

R2

COR3

O

+

4 36

R3C(OR4)339 6

Scheme 30.SchemeThis reaction led to the formation of bis(2-oxazolidinones)131 60Toda have reported130 the synthesis of cyclic carbamatesthrough the reaction of carbon dioxide with a-bromoacylophe-nones 55 in the presence of aliphatic primary amines in methanolto afford 3-alkyl-4-hydroxy-oxazolidone-2 derivatives 57 undermild reaction conditions (Scheme 36).previously xed on an aluminium porphyrin (Scheme 35).

O

R1 R2CO2+ NH

R'

R''+

R1

HO O

O

NR'

R''R2

aluminium porphyrin

52 36 4 53

Scheme 35.Kojima and co-workers have reported129 a carbamate synthesis53 from epoxides 52, amines 4 and CO2 36, where the latter was

53 54

Scheme 34.33.

hedr(Scheme 40).

R3X +R1

NHR2

CO2, DBU

R3 O

ON

R1

R26

432

Scheme 40.

Aresta and Quaranta have reported133 the synthesis of carba-mates 6 employing ionic species 45 through the alkylation withalkyl halides 32 using 18-crown-6 as a phase-transfer catalyst(Scheme 41).

2 RNH2 + CO2 RNH-COONH3RR' X

18-crown-6R' O

ON

H

R4 36 45

32In the above reaction, it was shown that there is an ionic species45 involved, which is formed when 2 mol of amine 4 was reactedwith CO2 36 (Scheme 39).

452 RNH2 + CO2 RNH-COONH3R

4 36Scheme 39.

An improvement in the yield of carbamate has been achieved byusing different basic reagents, which might be helpful in increasingthe nucleophilicity of the ionic species 45. Thus, Hori and co-workers have reported132 the synthesis of carbamates 6 throughthe reaction of primary and secondary amines 4, CO2, and alkylhalides 32 in the presence of a strong proton acceptor like DBUOBr

R

R'NH-COONH3R' O NR'

R

OH

O NR'

R

OH

+

61

45

62 63Scheme 38.Scheme 37.

The reaction of 2-(1-haloalkyl)-oxiranes 61with carbon dioxideand aliphatic primary amines gave ve and six-membered cycliccarbamates 62, 63 (Scheme 38).3a

OOD. Chaturvedi / Tetra6Scheme 41.OR3H(Scheme 45).

R3P + CCl4 [ R3P-CCl3] Cl

R3

HOH

NHR'R2

H

CO2-Et3N R3

H O

NR2

H

R'O

O

N

R'

O

R2

H

72 73

74

33-93%

75

PR3different alkyl halides 70 (Scheme 44).

R-(CH2)n-CH2.X R1

R2NH+

DBU-CO2 complex5 oC, 24 h, 80-98%

R-(CH2)n-CH2 O

O

N

R1

R270 4 71

Scheme 44.

Cyclic carbamates137 75 could be obtained in good yields(33e93%) under mild reaction conditions from amino alcohols74 and carbon dioxide using phosphorus(III) reagents 72 [i.e.,Ph3P, (PhO)3P] and halogenoalkanes (i.e., CCl4 and CCl3$CCl3) 73catalyst (Scheme 43).

Scheme 43.

Later, Perez and co-workers have reported136 the synthesis of N-alkyl carbamates 71 in good-to-excellent yields through a clean andmild transcarboxylation of several amines 4 with the previouslysynthesised DBUeCO2 complex and subsequent O-alkylation byHowever, this method was only useful for the preparation ofcarbamates from primary and secondary aliphatic amines. The ef-fect of several strong bases (CyTMG, TMG, DBU, MTDB, CyTEG, etc.)in increasing the nucleophilicity of 45 resulted in the formation ofcarbamates 6, studied by McGhee and co-workers134 They havedemonstrated the role of various strong bases in yielding O-alky-lated carbamate products using various kinds of alkylating agents(Scheme 42).

2 RNH2 + CO2 RNH-COONH3RR' X

base, 40-78% R' O

ON

H

R4 36 456

32

Scheme 42.

O-Allyl carbamates2c,135 69 could be obtained by the addition ofpreformed carbamate ion 67 [R$R0NHeCOO Hbase], generatedfrom various primary and secondary amines 4 and CO2, to a THFsolution of allylic chlorides 68 containing a palladium/phosphine

on 68 (2012) 15e45 25Scheme 45.

The use of Amberlite IRA 400 resin (basic resin) in the synthesisof carbamates 6 in high yields through the reaction of a variety ofalcoholic tosylates 78 with various amines 4 was also reported by

R379

4 6

Scheme 52.

A direct synthesis in high yields of carbamates 6 from the pri-mary alcohols 5 and amines 4 using a Mitsunobu reagent/CO2system has been rst reported by our group (Scheme 53).145

hedron 68 (2012) 15e452

R3 R,

R2

R3

O NR,

60oC, 2-4 h, 76-98%4R-(CH2)n-CH2.X R1R2

NH+ 3-5 h, 80-98%R-(CH2)n-CH2. O

O

N

R1

R2

Triton-B, CO2, 90-100oC

32 4 6

Scheme 49.

We have also reported142 the synthesis of carbamates 6 in highyields through the reaction of a variety of alcoholic tosylates 78with various amines 4 using the Triton-B/CO2 system (Scheme 50).

R

R1O.Tos

RHN+

R1C

OR

dry DMSO, Triton-B, CO2

6amines 4with primary and secondary alcohols 5 using gaseous CO2through a Mitsunobu reaction employing DBU and a DBAD/Bu3Psystem (Scheme 48).140

R1

NHR2

+ CO2 + DBU, DBAD/Bu3P100oC, 45 min., 46-96%

R3

R4HO

4 5N O

O

R1

R2

R3

R46

Scheme 48.

We have reported141 an efcient, one-pot, high-yielding protocolfor the synthesis of carbamates 6 through the reaction of variousamines 4 with variety of alkyl halides 32 using a benzyltrimethy-lammonium hydroxide (Triton-B)/CO2 system (Scheme 49).(Scheme 47).

OHRHN

R1

+ CO2O

N

R

OR3

76 77

Mitsunobu reaction

O

N

R

OR3

69-99%

Scheme 47.

More recently, they have further extended their protocol for thesynthesis of carbamates 6 through the reaction of secondaryOHHNR'

180 C, 16 h, 53-94% OR3

7475

Scheme 46.

The synthesis of cyclic carbamates 77 from amino alcohols 76involving sequential carboxylationwith carbon dioxide followed bya Mitsunobu reaction was reported by Dinsmore and Mercer.139

Unexpectedly, the stereochemical course of the Mitsunobu re-action is dependent on whether the carbamic acid intermediate isN-substituted with hydrogen (retention) or carbon (invertion)Tominaga and Sasaki have reported138 an efcient protocolfor the synthesis of 2-oxazolidinones 75 from CO2 and 1,2-aminoalcohols 74 catalysed by n-Bu2SnO affording 53e94% yields(Scheme 46).

R2 R3

+ CO2 o

N

R'

OR2

n-Bu2SnO

D. Chaturvedi / Tetra2678Scheme 50.R1NH + CO2 RCH CH CH Br+

R1NCOOCH CH CH R

zeolite-basedR1

R2NH + CO2 RCH2CH2CH2Br+

R1

R2NCOOCH2CH2CH2R

zeolite-Ycat.

4 32 6Scheme 55.

Srivastava and co-workers have also reported148 an efcientprotocol for the synthesis of carbamates 6 using CO2 mediated byzeolite-based organiceinorganic hybrid catalysts (Scheme 56).

2 2 2 2 2 2cat.The use of zeolite-based catalysts in the synthesis of carbamates6 was investigated by Srivastava and co-workers through the re-action of the corresponding amines 4, gaseous CO2 and alkyl halides32 over either titano-silicate molecular sieves or metal pthalocya-nine complexes encapsulated in zeolite-Y. The catalysts could beused with little or no loss in activity (Scheme 55).147

R3R5

R3R5

54

6

Scheme 54.5

Scheme 53.

Recently, the above method for the preparation of carbamates 6was further extended to a variety of primary, secondary and tertiaryalcohols 5 and amines 4, using the Mitsunobu reagent/CO2 system,by our group (Scheme 54).146

R2

R1OH

R4HN+ R2

R1

O C N

O R4dry DMSO, Mitsunobu reagent/CO2

90-100oC, 2-5 h, 76-98%R. (CH2)n. CH2.OH + R1 NH

R2

R. (CH2)n. CH2.OO

N R2

R1CO2 , Ph3P/DEAD

2-4 h, 80-98%4 6R2R3

O.Tos HNR,

+ R2

R3

O C N

R,

dry DMSO, basic resin/CO2100oC, 2.5-4 h, 70-98%

784

6

Scheme 51.

The utility of basic resin in the synthesis of carbamates 6 in highyields from the corresponding alkyl halides 32 and amines 4 usinggaseous CO2 was investigated by our group (Scheme 52).144

R2R3

R1X

RHN

R,+ R2

R1

O C N

O R

R,

dry DMSO, basic resin/CO2100oC, 2-4 h, 70-98%our group (Scheme 51).143

R1 RR1 O RR2 R24 32 6

Scheme 56.

Recently, Singh has reported the synthesis of various kinds ofmethyl carbamates 6 through the corresponding amines 4 andmethyl iodide 32 using a tetra-ethylammonium bromide-super-oxide/CO2 system (Scheme 57).149

Sasaki and Dixneuf have also reported154 the synthesis of 2-oxoalkyl substituted carbamates 85 in good yields through the re-action of secondary amines 4, a-ethynyl alcohols 84 and CO2 usingRu3(CO)12 as the catalyst (Scheme 62).

D. Chaturvedi / Tetrahedron 68 (2012) 15e45 27Scheme 60.

Later, Sasaki and Dixneuf have reported153 a direct synthesis ofvinyl carbamates 83 in good yields through direct the reaction ofsecondary amines 4 with acetylene 79 using gaseous CO2 in thepresence of a catalytic amount of RuCl3$3H2O (Scheme 61).

+ CO2+R2NHRuCl3.3H2O

90oC, 10-46%C

O

N

R1

R2O4 79

RRSasaki and Dixneuf have rst reported the synthesis of vinylcarbamates (80, 81 and 82), starting from diethylamine 4, and al-kynes 79 using CO2 in the presence of a ruthenium catalystRu3(CO)12 (Scheme 60). The overall yields of the products are poorin most of the reactions.the reaction of various amines 4 with a variety of alcohols 5 cata-lysed by tin complexes.151 The addition of acetals as dehydratingagents under a high CO2 pressure is the key to achieving high yields(Scheme 59).

R1NH2 + CO2 + HOR2R2O NHR1

Otin complexes

4 36 5 624-90%

200oC, 24 h,

Scheme 59.

152R24 638-90%Scheme 57.

Singh and co-workers have further investigated150 an improvedand efcient protocol for the synthesis of methyl carbamates 6,through the reaction of the corresponding amines 4 with methyliodide 32 using the tetra-ethylammonium bromide-superoxide/CO2 system under microwave conditions (Scheme 58).

R1HN

R2OMeCN

O

R2

R1KO2/Et4NBr/CO2

DMF, MW, 5-7 min.+MeI

432 677.5-95.5%

Scheme 58.

Carbon dioxide has been converted into carbamates 6 throughR1HN

R2OMeCN

OR1

KO2/Et4NBr/CO2DMF, rt, 2-7 h

+ MeI

3283

Scheme 61.Shim and co-workers have synthesised157 carbamates 89through the reaction of amines 88, acetylenic alcohols 84 and car-bon dioxide using a lanthanide catalyst. Thus, the reaction of per-hydroazepine 88 with 3,3-dimethyl-prop-1-yne-3-ol 84(R1R2Me) and CO2 in the presence of MCl3 (MCe, Pr, Nd, Gd)gave carbamate 89 (n6) in 20e38% yields. They have also pre-pared the carbamates (n4, 5) in 31 and 21% yields (Scheme 65).

(CH2)n NH +

R1

HO R2+ CO2

MCl3 (CH2)n N C O

O

R1

R289

20-38%

84CH2NHR + CO2[Ru]/PR'3

O N

O

R86

87

100oC, 8-48 h63-80%

Scheme 63.

Later, Dixneuf and co-workers have reported156 the synthesis ofvinyl carbamates 83 through the reaction of an alkyne 79 with anamine 4 using gaseous CO2 in the presence of various kinds of ru-thenium complexes, i.e., RuCl2(PR3)(carene) and RuCl2(nor-borna-diene)(pyridine)2 (Scheme 64). They have studied the catalytic roleof different Ru complexes in affording better yields of vinylcarbamates.

+ CO2+C

O

N

R1

R2O

79

83

RR

HN

R1

R2

Ru complex

3-67%

4

Scheme 64.Matsudo and co-workers have reported155 a synthesis of enolcarbamates 83 in good yields with high regio and stereoselectivitythrough the reaction of amines 4, terminal alkynes 79 and gaseousCO2 in the presence of a catalytic amount of (h4-cyclo-octadiene)(h6-1,3,5-cyclooctatriene)ruthenium [Ru(COD)(COT)]and a tertiary phosphine (Scheme 63). They have further extendedtheir methodology to the synthesis of cyclic enol carbamates 87using N-substituted propargyl amines 86 and CO2.

+ CO2+R2NH[Ru]/PR'3100oC, 8-48 h

C

O

N

R1

R2O4 79

83

RR

37-62%NH

R3

R4+ CO2 +

R2

R1OH

R2

R1 O

ON

O

R3

R4

Ru3(CO)1280oC, 20 h, 4-64%

484 85

Scheme 62.88 R1 = R2 = Me

Scheme 65.

NHR5R3

OH

R3

O N

OR54

9293

R1 +[M]/bipy, CO2 R1

100oC, 24 h, 30-97%

Scheme 67.

160

They extended their methodology to the synthesis of peptido-mimetics 97 and 99 using various kinds of protected amino acids 96and 98 (Scheme 72).

that the best yields (>87%) of carbamates could be achieved usinga DBU/CO2 system.

BnX + BnNH2CO2, base, solvent

Bn O

O

NHBnmetal carbonate32 4 6

Ph

H2N COOPh

BzCl, CO2, Cs2CO3TBAI, DMF, 23oC, 12 h

Ph

NH COOPh

O

PhH2CO

ClH2N COOMe

BzCl, CO2, Cs2CO3TBAI, DMF, 23oC, 24 h NH COOMe

O

PhH2CO

87%

92%

96 97

hedrprovide a carbonyl functionality in addition to its basic properties.Based on this concept, there aremany reports that have appeared inthe recent past on the use of metal carbonate/CO2 systems for thesynthesis of carbamates. Thus, Butcher has reported115 a carbamatesynthesis 6 in good-to-excellent yields (58e96%) from various alkylhalides 32 and amines 4 using the caesium carbonate/CO2 system(Scheme 69).

RCH2X +R1

NHR2

CO2, Cs2CO3

RH2C O

ON

R1

R2DMF, 58-96%32 4 6Scheme 69.Carbon dioxide providing the carbonyl functionality for thesynthesis of carbamates is not sufcient in itself in yielding highyields of desired carbamates. Therefore, several researchers haveconsidered that adding basic reagents to the reaction mixture mayincrease the basicity and nucleophilicity of the ionic species 45.Consequently, it has been proposed that metal carbonates, such asNa2CO3, K2CO3, Cs2CO3 etc. are good basic reagents, which could

R + CO2 + HN

R1

R2 R

O C

O

NR1

R2

8379 4100oC, 24 h, up to 55%

[Ru(TMHD)3]

Scheme 68.Recently, Bhanage and co-workers have reported the synthesisof vinyl carbamates83 through the reactionof variouskindsof alkynes79, amines 4, and CO2 using ruthenium tris(2,2,6,6-tetramethyl-3,5-heptanedionate) [Ru(TMHD)3] as a catalyst (Scheme 68).Dixneuf and co-workers have reported a regioselective syn-thesis of O-1-(1,3-dienyl)carbamates 91 through the regioselectiveaddition of CO2 and secondary amines 4 to isopropenylacetylene 90in the presence of [Ph2P(CH2)nPPh2]Ru(h3-CH2eC(Me)]CH2)2 asthe catalyst (Scheme 66). The yields were dependent on the natureof the ligand used in the catalyst. These workers found ligand withn2, afforded better yields of the products. The addition is favouredin the case of secondary cyclic amines.

90

91

R2NH + CO24 36

[ R2NCOO H2NR2]45 Ru cat., 20 h

100oC,

up to 80%

OR2N

O

Scheme 66.

Kim and co-workers have reported159 the synthesis of carba-mates 93 through the reaction of various kinds of propargyl alco-hols 92with variety of amines 4 using gaseous CO2 in the presenceof a catalytic amount of {Cu (X) (BF4)2 (X2, 5, 19, 22, tetraaza[6,6](1,10)-ferrocenophane-1,5-diene)} (Scheme 67).

R4R2 R2OR4158

D. Chaturvedi / Tetra28Later, Jung and co-workers have reported161 the synthesis ofcarbamates 95 in good-to-excellent yields using a solid-phaseScheme 74.A direct synthesis of N-alkyl carbamates 6 from primary amines4 and alkyl halides 32 using the caesium carbonate/CO2 system hasbeen reported by Jung and co-workers (Scheme 73).163

CO2/Cs2CO3,TBAI,DMF, 23oC, 20 h-6 d R' O

ON

R

R'RNH2

46

52-92%

+ R'X32

Scheme 73.

A study of the comparative yields of carbamates 6 using differ-ent metal carbonates and bases on O as well as N-alkylated prod-ucts was reported by Shi and Shen (Scheme 74).164 They realised98 99

Scheme 72.amines 4 with a variety of alkyl halides 32 using the caesium car-bonate/CO2 system in the presence of a catalytic amount of TBAI(Scheme 71).

RCH2X +R1

NHR2

CO2, Cs2CO3, TBAI

RH2C O

ON

R1

R2DMF, 23oC, 47-96%

32 4 6Scheme 71.Merrield resin 94 and caesium carbonate/CO2 and TBAI asa phase-transfer catalyst (Scheme 70).

Later, these workers have reported the synthesis of carba-mates162 6 in the solution phase through the reaction of variouskinds of structurally diverse aliphatic, aromatic and heterocyclic

ClR1

NHR2

+CO2, Cs2CO3, TBAI

DMF, 60oC, ~24 h 55-97%O

ON

R1

R2

94 954

Scheme 70.on 68 (2012) 15e45We have reported165 a convenient, high-yielding, one-pot syn-thesis of carbamate esters (70e90%) from the corresponding

R1

R2NH + CO2

R1

R2N OR

O

ROH+Cs2CO3

4 5 6up to 69%

Scheme 76.

Recently, a synthesis of radiolabelled carbamates 6 through the

hedrcarbon dioxide (O2/CO2) (Scheme 79).3.5.2. Electrochemical carbon dioxide. Inesi and co-workers haverst reported169 the synthesis of linear carbamates 6 and cycliccarbamates 35 from the corresponding amines 4, alkyl halides 32 orhaloalkylamines 34 using electrogenerated-superoxide activated

R1

NHR2

+ CO24

11 DBU, DMS in DMFN O

O

R1

R21 min, up to 96%

6

Scheme 78.R1

R2NH +

R1

R2N OR

O

RCH2Cl4 32 6

DBU, 11CO275oC, 10 min,

77%

11C

Scheme 77.

A synthesis of labelled carbamates 6 has been reported byWilson and co-workers through the trapping of labelled CO2with amines 4 using a methylating agent, i.e., dimethylsulphate(Scheme 78).168incorporation of [11C]eCO2 using various kinds of alkyl halides 32,amines 4 and catalytic amount of DBU was reported by Hooker andco-workers (Scheme 77).167alcoholic tosylates 100, and amines 4 using the K2CO3/CO2 systemin the presence of a catalytic amount of tetra-n-butylammoniumiodide (Scheme 75). This method has been used for carbamatesderived from various aliphatic primary, secondary and aromaticamines.

RCH2OTosR1

R2NH

dry DMSO, anhyd. K2CO3

TBAI, CO2, 90-100oC, 5-6 h, 70-90%RCH2 O

ON

R1

R2+

100 4 6

Scheme 75.

Vos and co-workers have reported166 an efcient and greensynthesis of carbamates 6 through the coupling of various amines 4with variety of alcohols 5 using the Cs2CO3/CO2 system (Scheme 76).

D. Chaturvedi / TetraScheme 79.corporation into aziridines 103 under mild electrochemical condi-tions (Scheme 84). Out of several Ni catalysts used, Ni(bipy)3(BF4)2from the corresponding amines 4, and alkyl halides using electro-chemical carbon dioxide-saturated room temperature ionic liquid[Bmim]BF4 solutions (Scheme 83).

R1

R2NH + CO2

[Bmim]BF4, eEtI, up to 82%

R1

R2N OEt

O

4 6Scheme 83.

Dunach and Tascedda have reported174 a new and selectiveelectrochemical procedure for the synthesis of ve-membered-ringcyclic carbamates 104 and 105 involving nickel-catalysed CO2 in-Scheme 81.

The utility of an electrochemically generated cyanomethyl an-ion/carbon dioxide system in affording high yields of carbamates 6using various kinds of amines 4 and alkyl halides 32 was furtherinvestigated by Inesi and co-workers (Scheme 82).172

NHR1R2

NR1R2

OEt

O

4 6up to 96%

CH2CN/CO2EtI

Scheme 82.

Inesi and co-workers have reported173 a new electrochemicalprocedure for the synthesis of carbamates 6 in high yields, startingtrochemical synthesis of chiral oxazolidin-2-ones 75, starting fromthe corresponding chiral 1,2-amino-alcohols 74. Subsequent CO2bubbling and addition of tosyl chloride afforded the desired cycliccarbamates 75 in high yields (Scheme 81).

H2N OH

R1 2. CO23. TsCl

HN O

O

R15747

MeCN-Et4NClO4e1. 66-88%R2 R2sequential addition of CO2 and ethyl iodide, affording the carba-mates in high yields.

NH

O

e , MeCN, Et4NClO4

N ONEt4

1. R2NH

2. CO23. EtI

R2N-COOEt

101102

6

33-89%

Scheme 80.

Inesi and co-workers have also reported171 an improved elec-Later, Inesi and co-workers have reported170 the synthesis ofcarbamates 6 using carbon dioxide through an electrochemicalprocess (Scheme 80). This synthesis is based on the reaction ofamines 4 with the electrochemically generated base 102 (associ-ated with the Et4N cation) from 2-pyrrolidone 101 followed by

on 68 (2012) 15e45 29was shown to be efcient for this transformation and afforded 100%yields of the desired carbamates.

NR'

R

+ CO2(1 atm.)

N O

O

Ni(II) + e R'

R

O N

O

R

R'

DMF, rt+

103 104 10575-100%

Scheme 84.

Lu and co-workers have reported175 a new and efcient elec-

D. Chaturvedi / Tetrahedr30NH2R3scCO2, CuI

+

R2

R1OH

4

84

60oC, 12-24 h

R1, R2 = alkyl, aryl

R1 = alkyl, aryl, HR2 = H

O N

O

R1R2

R3

O N

O

R3

106

32-95%

88-96%action of phenylacetylene 79 with diethylamine 4 usingsupericritical CO2 (Scheme 87). They have also studied the effect oftemperature on the catalytic activity of Ru complexes and foundthat the best yields of vinyl carbamates were obtained at 120 C.

Ph + CO2 + HN

R1

R2 Ph

O C

O

NR1

R2RuCl3.xH2O

3 h, 60-120oC83 (E and Z)

79 4100%

Scheme 87.rst reported176 the synthesis of carbamates 6 in good yields,starting from the corresponding amines 4 and alkyl halides 32using supercritical CO2/K2CO3 in the presence of tetra-n-alky-lammonium halides acting as phase-transfer catalysts (Scheme 86).They have also demonstrated the role of different phase-transfercatalysts on carbamate synthesis and found that tetra-n-butyl-ammonium bromide was the best in affording high yields ofcarbamates.

R1

R2NH + R3X + K2CO3

R1

R2N

CO

O

onium salt, CO2 R34 32

1- 4 h,72-94%

6Scheme 86.

Baker and co-workers have reported177 a solvent-free ruthe-nium-catalysed synthesis of vinyl carbamates 83 through the re-trochemical synthesis of carbamates 6 through the electrochemicalincorporation of carbon dioxide into amines 4 catalysed by anelectrogenerated Ni complex [Ni(bipy)3Cl2] using tetra-ethyl-ammonium bromide (Scheme 85).

R1

R2NH + CO2

e

EtI, up to 82%

R1

R2N OEt

O

4 6

Ni(bipy)3Cl2

Scheme 85.

3.5.3. Supercritical carbon dioxide. Yoshida and co-workers haveR1107

Scheme 88.Strong bases, such as alkali metal alkoxides as well as Zn, Co, Snand Al compounds, have been widely employed as catalysts inthe carboalkoxylation of anilines and, more generally, of aro-matic amines.185 Moreover, Lewis acids, such as AlCl3, SnCl2,ZnCl2, Zn(OAc)2$2H2O, FeCl3, or metal (Rh,Ru) complexes, haveproved to be effective in promoting the conversion of n-propyl-amine and diethyl carbonate selectively into n-propylethylcarbamate.182

Primary and secondary aliphatic amines can react with CO2according to the equilibrium shown in Eq. 1 to afford themonoalkylammonium-alkylcarbamate (MAAAC) ion121 45 thatserves as a convenient source of the carbamate moiety in thesynthesis of carbamates using DMC (Scheme 91).186 O-Carbome-thoxylation of the carbamate anion is the rst step (Eq. 2) toafford a mixed carbamicecarbonic anhydride RNHeCOOCOMe111. This step could be catalysed by acidic species, such as RNH3

or RNHeCOOH, present in the equilibrium. Selective de-carboxylation of 111 through the expulsion of a CO2 molecule3.5.4. Organic carbonates with carbon dioxide. Organic carbonatesconstitute an important source for the carbonyl functionalityduring the synthesis of carbamates. Their reaction with aminesrepresents an alternative synthetic route to carbamates that hasgained growing attention in the last few years as a non-phosgene route to the synthesis of organic carbamates.181

Nowadays, dimethyl carbonate (DMC) 110 can be produced ona large scale by the oxidative carbonylation of methanol.182

Other organic carbonates can be easily obtained by trans-esterication of DMC with phenols183 and long-chain high-boiling alcohols.184 The reaction between primary and secondaryamines and dialkyl carbonates needs a suitable catalyst in orderto obtain satisfactory conversion rates and high selectivities.Recently, Jiang and co-workers have demonstrated178 a new andefcient protocol for the synthesis of oxazolidinones 106 andoxazolones 107 through the cycloaddition reaction of CO2 withpropargyl alcohols 84 and amines 4 under supercritical conditions(Scheme 88).

Ikariya and co-workers have reported179 the stereoselectivesynthesis of Z-alkenyl carbamates 83 from the correspondingamines 4 and alkynes 79 using a CO2-soluble ruthenium-P(OEt)3catalyst under supercritical conditions (Scheme 89).

R + HN

R1

R2

O C

O

NR1

R2scCO2, 15 h, 80oC83 (Z)79 4 31-68%

RRuCl2{P(OEt)3}4

Scheme 89.

Ikariya and co-workers have also reported180 the synthesis of 5-vinyl-1,3-oxazolidin-2-ones 109 through the carboxylative trans-formation of 2,3-allenic amines 108 and CO2 promoted by palla-dium catalysts under supercritical conditions (Scheme 90).

R1

NHR2

108

Pd(OAc)2scCO2, 50oC, 15 h NO

O

R2

R1

up to 65%

109Scheme 90.

on 68 (2012) 15e45from the carbamic moiety leads to the formation of carbamate 6(Eq. 3).

2RNH2 + CO2 RNH-COONH3R45

45 + COMe

OMeO

(eq. 1)

COMe

OO

C

O

NHR+ MeOH (eq. 2)

111

111 COMe

ONH2R

6

(eq. 3)+ CO2

4

110

Scheme 91.

Organic carbonates have received much attention in recentyears as cheap and safe alternatives to the non-phosgene routes forthe synthesis of organic carbamates. Therefore, several researchersin different countries have become interested in synthesising car-bamates through this route.

Ogura and co-workers have rst reported187 an efcient syn-thesis of N-succinimidyl carbamates 113 through the reaction of thecorresponding amines 4 with N,N0-disuccinimidyl carbonate (DSC)112 using triethylamine (Scheme 92).

the corresponding amines 4 with benzotriazole carbonates 114(Scheme 93).

NN

N

O

O

OR

+ HNR2

R1

114

N

O

OR

R1

R2 64

rt, 0oC

53-98%

Scheme 93.

The use of N,N0-disuccinimidyl carbonate 114 has been furtherexplored for the synthesis of carbamates189 118 from azides 117 andmixed carbonates 116 obtained from 115 by Ghosh and co-workers(Scheme 94).

Ghosh and co-workers have also reported190 the synthesis ofcarbamates 122 in high yields, starting from the correspondingamines 121 and a mixed carbonate 120, which is obtained througha reaction of alcohol 119 with DSC 114(Scheme 95).

Chiral carbamates 125 have also been synthesised through anenzymatic alkoxy-carbocyclisation reaction with vinyl carbonates123 and racemic amines 124 using Candida antarctica lipase (CAL),was reported by Pozo and Gotor (Scheme 96).191

Gotor and co-workers have reported192 the chemoenzymaticsynthesis of a 20-deoxynucleoside urethane. 20-Deoxynucleoside-50-and 30-(N-alkyl)carbamates (129 and 131) were synthesised ina two-step procedure using lipase catalysis in the regioselectivevinyloxy carbonylation, starting from 96 and 97 through theinvolvement of intermediates 128 and 130 (Scheme 97). Theregioselectivity of the reaction depends upon the type oflipase enzyme used. Total regioselectivity is obtained in the

Aresta and co-workers have reported193 the synthesis of car-bamates 6 through the reaction of aromatic amines 4 with DMC110 or diphenyl carbonate (DPC) 132 in the presence of organo-phosphorous acids [Ph2P(O)OH, (PhO)2P(O)OH, or (BuO)2P(O)OH/(BuO)P(O)(OH)2 equimolar mixtures] (Scheme 98). They havefurther realised that better yields of carbamates were obtainedusing DPC.

Urpi and co-workers have reported62d an efcient protocol for

me

O

D. Chaturvedi / Tetrahedron 68 (2012) 15e45 31115OH Et3N, MeCN, 23oC

114Later, Ogura and co-workers have demonstrated188 an efcientprotocol for the synthesis of carbamates 6 through the reaction of

O

O

ON

O

O

N

O

O 112

+ HNR2

R1

4

ScheSchemethe synthesis of tert-butyl carbamates 6 through the reaction of

O

ON

O

OO

OO

N3

OO

O

OO

NH O

O

+

O

O

H2, 10% Pd/CEt3N, THF

711611

118

69-80%presence of PS lipase and only a small amount of the regiose-

lective product is obtained when the reaction is catalysed by CAlipase.

Et3N, rt

5-10 h, 50-90%

O

ON

O

O

NR1

R2

113

92.94.

114O

O

O

TBSO

HO Et3N, MeCN, rt, 4 h O

O

ON

O

O

O

O

O

OTBS

O

O

O

O

O

OTBS

O

O

Ph

H

NH2

O

O

Ph

H

NH

Et3N, CH2Cl2rt, 3 h

119 120

121

122

65-89%

me 95.

ArNH2 + RO OR

O

P-acidArHN OR

O

64

110, R = Me132, R = Ph

15-76 h, up to 98%

Scheme 98.

D. Chaturvedi / Tetrahedron 68 (2012) 15e4532Sche

CRO O

O

H2N R+ CAL C

RO

O

NH

R

123 124 125

20-72 h, 38-45%up to 98% ee

Scheme 96.azides with trimethylphosphine 133 followed by the addition of 2-(tert-butoxycarbonyloxyamino)-2-phenyl acetonitrile 134 to 135 at20 C (Scheme 99).

Chandrasekhar and co-workers have reported194 an excellentone-pot method for the synthesis of carbamates 6 through thereaction of azides or Cbz-protected amines with di-tert-butyldicarbonate (Boc)2O 136 using an inexpensive and safe hydridesource, i.e., polymethylhydrosiloxane (PMHS) under PdeC catalysis(Scheme 100).

The lipase enzyme has also been used as a catalyst in the syn-thesis of chiral carbamates195 138, starting from racemic amines 4and alkylvinyl carbonates 137 (Scheme 101).

Leunaire and co-workers have reported196 an efcient synthesisof carbamates 6 through the reaction of amines 4 with DMC 110catalysed by g-Al2O3 (Scheme 102).

+

O BHO

HO

C

O

O O N

O BHO

OO

O

PSL, THF, 30oC

CAL, THFO BO

HO

O

O

O BO

HO

RHN

ORNH2, THF, 80-100oC

O BHO

ORHN

ORNH2, THF, 80-100oC

127126

130 131

128

129

30oC, 128a5oC, 128b

129a, 70%129b, 75%

80-100%131a, 80%131b, 52%

Scheme 97.

O

O

OButN

CN

Ph

RN3

Me3P

RN=PMe3+-20oC, rt

134135

133

NH

O

OButR

65 h, 87-100%

Scheme 99.

1 1 2

Scheme 105.

Sodeoka and co-workers have reported200 a convenient methodfor the synthesis of carbamates 6 through the reaction of variousamines 4 with a variety of polymer-supported N-hydroxysuccinimide-substituted carbonates 140 (Scheme 106).

Later, Christensen and co-workers have reported201 the syn-thesis of carbamate-protected polyamines (145e147, 149, 150 and151) from 144 and 148 using alkyl phenyl carbonates (141e143).This is an economical, practical and versatile method for the se-lective Boc, Cbz and Alloc protection of polyamines. This methodallows Boc, Cbz and Alloc protection of primary amines in thepresence of secondary amines by reaction of polyamines with alkylphenyl carbonates. In addition, this method allows the mono-

D. Chaturvedi / TetrahedrScheme 101.Scheme 100.Chaudhari and co-workers have reported197 efcient protocolfor the synthesis of carbamates 6 through the reaction of variouscarbonates (R2Me, 110; R2Ph, 132) with a variety of amines 4catalysed by silica-gel (Scheme 103).

Scheme 103.

Carloni and co-workers have reported198 synthesis of carba-mates 6 through the reaction of diethyl carbonate 139 with a vari-ety of amines 4 using a heterogeneous catalyst-a hybrid organic/inorganic material prepared by anchoring TBD to MCM-41 silica(Scheme 104).

carbamation of simple symmetrical aliphatic a,u-alkanediaminesin high yields with respect to the diamine. Furthermore, themethod allows the selective carbamate protection of a primaryamine located on a primary carbon in the presence of a primaryamine located on a secondary or a tertiary carbon in excellent yields(Scheme 107). The alkyl phenyl carbonates investigated in this

Scheme 1

Scheme 104.

Scheme 102.study were tert-butyl phenyl carbonate (141), benzyl phenyl car-bonate (142) and allyl phenyl carbonate (143), which introduces theBoc, Cbz and Alloc protecting groups.

Scheme 107.06.Selva and workers have reported199 an efcient synthesis of car-bamates 6 from primary aliphatic amines 4 with dialkyl carbonates(R Me, 110; R Ph, 139) in supercritical CO (Scheme 105).

on 68 (2012) 15e45 33Curini and workers have reported202 that ytterbium triate,Yb(OTf)3, can be efciently used for the preparation of carbamates

presence of potassium carbonate and tetra-n-butylammoniumbromide under solvent-free conditions (Scheme 113).

hedron 68 (2012) 15e45n-butyltin oxidewas found to be the best in affording good yields ofthe carbamates.

Scheme 112.Scheme 111.

Chaudhari and co-workers have reported the synthesis of car-bamates206 6 through the reaction of various organic carbonates(RMe, 110; RPh, 132; REt, 139) with various amines 4, usingvarious catalysts (Scheme 112). Out of the several catalysts used, di-Scheme 110.

Chandrasekhar and co-workers have reported205 the one-stepconversion of N-benzyl, N-trityl and N-diphenyl amines 152 intotert-butyl carbamates 6 using (Boc)2O 136 the presence of poly-methylhydrosiloxane (Scheme 111).Scheme 109.

Conversion of azides into tert-butyl carbamates204 6 could alsobe achieved using di-tert-butyl dicarbonate 136, decaborane(20 mol %) and 20% PdeC at room temperature in methanol(Scheme 110).6, through the reaction of various amines 4 with DMC 110 undersolvent-free conditions (Scheme 108).

Scheme 108.

Deng and co-workers have reported203 the synthesis of carba-mates 6 through the reaction of primary and secondary aliphaticamines 4 with DMC 110 using ionic liquids (Scheme 109).D. Chaturvedi / Tetra34Shen and Jiang have reported207 a facile synthesis of N-methylN-aryl carbamates from aromatic amines 4 and DMC (110) in theThe pressure of CO2 largely inuences both the reaction conversionand the selectivity towards urethanes. Generally, conversion goesthroughamaximum(70e80%) in themid-range (40bar) anddropsatlower and higher pressures, whereas selectivity is continuously im-proved (from 50 up to 90%) by an increase of pressure.phenyl)carbonate 154 with aliphatic amines 4 under mild reactionconditions (Scheme 116).

Scheme 116.

Later, Selva andco-workershave reported211 ahigh-yielding, one-pot synthesis of methyl carbamates 6 from primary aliphatic amines4 anddimethyl carbonate (110) using supercritical CO2 (Scheme117).amines 4 in the presence of a group III metal (Sc, La) triate catalystunder mild conditions to afford the corresponding carbamates 6 inhigh yields (Scheme 115). They have optimised the effect of thevarious catalysts at different temperatures, times and molar ratiosof amines on the yields of the carbamates. Sc(OTf)3 is more effectivethan the La salt.

Scheme 115.

Simon and co-workers have reported210 an efcient synthesis ofo-nitrophenyl carbamates 6 through the reaction of bis(o-nitro-triates, under mild reaction conditions (Scheme 114). Sc(OTf)3 ismore effective than the La salt.

Scheme 114.

Distaso and Quaranta have also reported209 the carbomethy-lating reactivity of methyl phenyl carbonate 153 towards aromaticScheme 113.

Distaso and Quaranta have reported208 a high-yielding synthesisof carbamates 6 through the reaction of various aliphatic amines 4and dimethyl carbonate (110) catalysed by group III metal (Sc, La)Scheme 117.

3fective among the applied ionic liquids.

N-Heterocyclic carboxymethylation of amines 4, using DMC(110) catalysed by an ionic liquid, afforded the correspondingcarbamates 6 in high yields, reported by Gao and co-workers(Scheme 124).218

Recently, Sureshbabu and Hemantha have reported219 the syn-thesis of dipeptidyl carbamates 162 through the reaction of anamino acid 161 with their synthesised F-moc aminoalkyl penta-uorophenyl carbonate 160. They have further explored the utilityof 160 in the synthesis of oligopeptidyl carbamates using a varietyof amino acids (Scheme 125).

Recently, an efcient preparation of N-tert-butyl carbamates 6 ofvarious amines 4 using di-tert-butyl dicarbonate 136 in the pres-ence of Amberlyst 15 under solvent-free conditions was reportedby Pal and co-workers (Scheme 126).220

More recently, an efcient and chemoselective protocol for thepreparation of N-tert-butyl carbamates 6 of various amines 4 using

Scheme 122.

Scheme 123.

Scheme 124.

Scheme 125.

Scheme 126.

hedrThe use of DMC (110) in the synthesis of methyl phenyl carba-mates 6 using aromatic amines and an ordered AISBA-15 catalystwas recently reported byHalligudi and co-workers (Scheme 121).215

Recently, Yoshida and co-workers have reported216 an efcientprotocol for the synthesis of 5-vinylideneoxazolidin-2-ones 159 bya DBU-mediated CO2-xation reaction of 4-(benzylamino)-2-butynyl carbonates/benzoates 158 (Scheme 122).

The use of DMC (110) was further explored in the synthesis of

Scheme 121.Han and Porco have reported214 an efcient protocol for thesynthesis of structurally diverse carbamates 6 through the reactionof various amines 4 with variety of carbonates (110, 132, 139 etc.)using a zirconium(IV)-catalysed exchange process with 2-hydroxypyridine as a catalytic additive (Scheme 120).

Scheme 120.Later, Li and co-workers have reported213 the synthesis ofmethyl phenyl carbamates 6 through the reaction of dimethylcarbonate (110) with 1,3-diphenyl urea 157 under atmosphericpressure (Scheme 119). Among the various catalysts that wereused, NaOMe was found to be best in affording high yields ofcarbamates.

Scheme 119.Scheme 118.Deng and co-workers have reported212 the synthesis of carba-mates 6 and dicarbamates 156 through the reaction of variety ofaliphatic amines 4 and bis-amines 155with dimethyl carbonate 110catalysed by acid-functionalised ionic liquids (Scheme 118). Theyfound that eSO H functionalised ionic liquids were the most ef-

D. Chaturvedi / Tetramethyl N-phenyl carbamates 6 from aromatic amines 4 catalysedby a ZnOeTiO2 catalyst (Scheme 123).217on 68 (2012) 15e45 35di-tert-butyl dicarbonate 136 in the presence of tungstophosphoricacid (TPA)-supported ordered mesoporous silica (SBA-15) under

Iwasaki and co-workers have reported223 the synthesis of hy-droxy carbamates 6a and 6b from cyclic ve-membered carbonates167 and primary amines 4 at room temperature (Scheme 129).

3.6. Carbamate synthesis from dithiocompounds

thiocarbamates during three steps is 36%, whereas the direct con-version afforded a 95% yield.

Recently, Fochi and co-workers have reported an efcient pro-tocol for the synthesis of various kinds of carbamates 6 through thereaction of the corresponding thiocarbamates 170 with alcohols 5in triethylamine (Scheme 131).225

3.6.2. From carbon-imido dithiolates. Rajappa and co-workers have

be converted into carbamates 6 through a one-step synthesis(Scheme 132).

3.7. Carbamate synthesis through rearrangement reactions

3.7.1. Hoffmann rearrangement. Generally, the Hoffmann rear-rangement229 converts primary carboxamides into amines usingaqueous NaOH and Br2. In recent years, it has been used for thesynthesis of carbamates 6 through the involvement of an iso-cyanate intermediate. Several researchers have focused their effortson this rearrangement reaction in order to achieve an efcientsynthesis of carbamates.

Moriarty and co-workers have reported230 an efcient protocolfor the synthesis of methyl carbamates 6 from primary alkyl andaryl carboxamides 173 using hypervalent iodine. They have treateda series of primary alkyl/aryl carboxamides 173 with PhI(OAc)2 inKOHeMeOH at 5e10 C to afford the corresponding methyl car-bamates 6 in good-to-excellent yields (Scheme 133). These

Scheme 129.

Scheme 131.

Scheme 132.

hedron 68 (2012) 15e45reported226 that carbon-imido dithiolates 171 are important pre-cursors for the synthesis of carbamates 6 and can be rst convertedinto S-methyl thiocarbamates227 172 using zeolite-catalysed partial3.6.1. Using dithiocarbamates/thiocarbamates. Tandel and co-workers have reported an efcient synthesis of carbamates 6from dithiocarbamates 168 through either a series of trans-formations via 169 and 170 or direct conversion using NaOMe/MeOH (Scheme 130).224 The overall yield of carbamates from di-Scheme 128.solvent-free conditions was reported by Karmakar and Banerji(Scheme 127).221

Recently, A direct conversion of various allylic imines 164 intotheir corresponding a-ethoxy carbamates 166 using diethyl pyro-carbonate 165 was reported by Grognec and co-workers (Scheme128).222 The imines were synthesised from the corresponding al-dehydes 163 using allylic amines 4.

Scheme 127.

D. Chaturvedi / Tetra36hydrolysis. This method therefore provides an alternative route tomethyl carbamates 6.228 The carbon di-imido dithiolates can alsoScheme 130.Scheme 133.

conditions avoid the use of elemental bromine or heavy metal re-agents, such as Pb(OAc)4, AgOAc and Hg(OAc)2, while taking ad-vantage of the commercial availability of PhI(OAc)2.

Later, Huang and Keillor have reported231 synthesis of methyl

yields under extremely mild conditions.Gogoi and Konwar have reported237 a synthesis of methyl car-

bamates 6 through a modication of the Hoffmann rearrangement.Thus, a series of methyl carbamates 6were synthesized in good-to-

A recent method for the synthesis of carbamates 6, starting from

3.7.2. Curtius rearrangement. The Curtius rearrangement involvesthe pyrolysis of acyl azides 175 to yield isocyanates 13 (Scheme

Scheme 134.

Scheme 135.

Scheme 136.

Scheme 138.

Scheme 139.

Scheme 140.

Scheme 141.

D. Chaturvedi / TetrahedrLater, Matsumara and co-workers have reported234 the elec-trochemical synthesis of carbamates 6 from primary carboxamides173. The process has been referred to as an electrochemically in-duced (EI) Hoffmann rearrangement, which was developed usingnew solvent systems containing a variety of alcohols 5, the reactionproceeding under mild conditions (neutral). An epoxy functionalgroup in the amide and alcohol remains intact during the elec-trolysis (Scheme 137).The synthesis of N-tert-butoxy carbamates 6 from primary car-boxamides 173 using a copper(II) reagent (prepared from copper(II)bromide and lithium tert-butoxide, i.e., CuBr2eLiOtBu), affordinggood-to high-yields, has been reported by Yamaguchi and co-workers (Scheme 136).233They have further elaborated232 the synthesis of methyl carba-mates 6 through the involvement of a Hoffmann rearrangementusing NBS and DBU in methanol (Scheme 135). This method hasbeenwidely used for the conversion of alkyl and aryl carboxamides173 into their corresponding methyl carbamates 6 in excellentcarbamates 6 via a modied Hoffmann rearrangement. They havetreated a series of p-substituted aromatic and primary aliphaticcarboxamides 173 with NBS and NaOMe in methanol heated toreux for 10 min for the conversion of the carboxamides into theircorresponding primary amino methyl carbamates 6 in nearlyquantitative yields (Scheme 134). The mild oxidative conditions ofthis modied Hoffmann rearrangement are shown to be particu-larly useful for the preparation of p-substituted anilines.Scheme 137.142).239 Isocyanates 13 can be treated with alcohols 5 to affordthe corresponding carbamates 6. In recent years, much interest hasbeen developed among the chemists to synthesise carbamatesthrough the Curtius rearrangement by trapping of the isocyanateintermediate 6 with an alcohol 5.

Richer and Andersen have reported240 the synthesis of carba-the corresponding amines 173 through a Hoffmann rearrangementusing a microreactor technique has been reported by Ley and co-workers (Scheme 141).238excellent yields using NaOCl as an oxidant in the presence of KF/Al2O3/MeOH under reux conditions (Scheme 140).Nishikawa and co-workers have reported the synthesis ofcarbamates 6 through the rearrangement reaction of tri-chloroacetamides 174 using variety of alcohols 5 (Scheme 139).236Hiegel and Hogenauer have reported235 a base-catalysed syn-thesis of N-substituted carbamates 6 through the rearrangement ofN-chloroamides (Scheme 138). These N-chloroamides were ob-tained by the chlorination of amides 173 using trichloroisocyanuricacid (TCICA).

on 68 (2012) 15e45 37mates 177 in excellent yields using a solid-supported polystyreneresin. They have prepared an acid azide derivative 176, which was

previously loaded on to a polystyrene resin and treated with theappropriate alcohol in m-xylene (Scheme 143).

dicarbonate 136 and sodium azide allowed the formation of theacyl azides 175, which undergo a Curtius rearrangement in thepresence of tetrabutylammonium bromide and zinc(II) triate toafford the corresponding carbamates 6 through trapping of theisocyanate intermediate (Scheme 144). They have extended thesame protocol to the direct synthesis of carbamates of aromaticamines using aromatic acids.242,243

kind of approach was adopted by Saigo and co-workers for thesynthesis of fullerene carbamates through the reaction of the cor-responding fullerene acid azide with an alcohol.245

3.7.3. Lossen rearrangement. The Lossen rearrangement is a usefulchemical reaction in which O-activated hydroxamic acids 179 canbe converted into the corresponding isocyanates 13 (Scheme147).239b,248 Carbamates can be synthesised through in situ trap-ping of the isocyanate intermediate 13 with an alcohol 5. In recentyears, based on the above concept, researchers have become in-terested in synthesising carbamates using hydroxamic acids

Recently, Papot and co-workers have reported an efcient syn-thesis of carbamates 6 through the reaction of a hydroxamic acid179 with an alcohol 5 promoted by 2,4,6-trichloro-1,3,5-triazine180 (cyanuric chloride; TCT) in the presence of an excess of N-methyl morpholine (NMM) through Lossen a rearrangement re-action (Scheme 148).249

A recent method for the synthesis of carbamates 6 through thereaction of hydroxamic acids 179 with an alcohol 5 using N,N0-carbonyl di-imidazole (CDI) through a Lossen rearrangement was

250

Scheme 142.Scheme 146.

Scheme 147.

Scheme 148.

hedrScheme 145.Dussault and Xu have reported a direct conversion of variousacid azides 175 into their corresponding carbamates 6 througha Curtius rearrangement using ethanol 5 (Scheme 145).244 A similar

Scheme 144.Lebel and Leogane have reported241 an efcient protocol for thepreparation of tert-butyl carbamates 6 from the correspondingacids 178. The reaction of carboxylic acids 178 with di-tert-butyl

Scheme 143.D. Chaturvedi / Tetra38Iklegami and co-workers have reported a synthesis of carba-mates 6 of various sugar and other functionalities using the cor-responding acids 178. In situ conversion of acids 178 to thecorresponding azides 175 was achieved using diphenyl phosphorylazide (DPPA), followed by the addition of an alcohol to afford thecorresponding carbamates (Scheme 146).246 They have furtherexplored this methodology for the synthesis of carbamate-linkedglycoconjugates using various kinds of sugar acids and DPPA.247reported by Dube and co-workers (Scheme 149).

Scheme 149.through the Lossen rearrangement reaction.on 68 (2012) 15e453.8. Miscellaneous methods

3.8.1. Carbamate synthesis using carbonyl di-imidazole. Fischer hasreported the synthesis of imidazole carbamates 6 through the re-action of N,N-carbonyl di-imidazole 180 (CDI) with variety of al-cohols 5 under very mild conditions (Scheme 150).251

The use of imidazolium salt 181 as better leaving group duringthe reaction with an alcohol 5 to afford carbamates 6 in high yieldswas reported by Batey and co-workers (Scheme 151).252

3.8.2. Carbamate synthesis using sodium cyanate. Recently, the useof sodium cyanate 182 in the synthesis of primary carbamates 6through the reaction with alcohols 5 using various kinds of acidiccatalysts, such as trichloroacetic acid, silica supported-sufuric acid,silica supported-perchloric acid and Al(HSO4)3 has been realised byModaressi-Alam and co-workers (Scheme 152).253e256

Later, Wood and co-workers have reported259 a novel, one-stepconversion of primary alcohols 5 into carbamate-protected amines6 using a benzyl Burgess reagent 185 (RBn) (Scheme 155).

Scheme 150.

Scheme 151.

Scheme 154.

Scheme 156.

hedrD. Chaturvedi / Tetra3.8.3. Carbamates synthesis using Burgess reagent. The Burgess re-agent257 185 is prepared from a reaction of an alcohol 5 withchlorosulfonyl isocyanate 183 and triethylamine 184 (Scheme 153)and has been shown to be efcient for the stereospecic cis-dehydration of secondary and tert-alcohols to provide olens. Pri-mary alcohols do not undergo elimination, due to a competing (andpredominant) displacement reaction to form the correspondingmethyl carbamates. Several kinds of alcohols have been used, inorder to obtain a more efcient Burgess reagent, which could affordcarbamates in high yields. In recent years, researchers have di-rected their efforts to synthesising carbamates through the Burgessreagent.

Nicolaou and co-workers have reported258 an efcient, one-potsynthesis of methyl carbamates 187 through the corresponding cis-

transcarbamoylation reaction has important industrial applicationsin the eld of polyurethane chemistry, especially for coatings.261 Inrecent years, many researchers have directed their efforts for syn-thesising carbamates through the transcarbomoylation approach.

Rannard and Davis have reported262 an efcient synthesis ofcarbamates of higher bis-amines, such as 190 through the reactionof imidazole carbamate 6 with bis-amines, e.g., 191 (Scheme 157).

Later, Jousseaume and workers have reported263 the conversion

Scheme 152.

Scheme 153.

Scheme 157.of a carbamate into its higher homologue using bismuth catalystsfor transcarbamoylation (Scheme 158). They have further studiedthe effect of various catalysts (e.g., Bi, Sn, Sc, Sm, Yb, La) on the yield3.8.4. Carbamate synthesis through transcarbamoylation. A reagentfor mediating the conversion of one carbamate compound into itshigher or lowerhomologue is knownas transcarbamoylating reagentand the reaction is referred to as a transcarbamoylation reaction. TheConversion of BayliseHillman adducts 188 of b-amino acids intothe corresponding methyl carbamates 189 using a methyl Burgessreagent 185 was reported by Mamaghani and Badrian (Scheme156).260

Scheme 155.diols 186 using a methyl Burgess reagent 185 (RMe) (Scheme154).

on 68 (2012) 15e45 39of the transcarbamoylated product and observed that bismuthcompounds gave very good yields.

Later, Li and co-workers have reported the synthesis of methylN-phenyl carbamate 6b through the reaction of aniline 4 withmethyl carbamate 6a in the presence of a catalyst (Scheme 160).265

They have optimised the activity of various catalysts and found that

Recently, Shimizu and Sodoeka have reported the synthesis ofvarious structurally diverse carbamates 6 through the reaction ofa variety of amines 4 with 1-alkoxycarbonyl-3-nitro-1,2,4-triazoles

266

3.8.5. Carbamate synthesis using ureas and alcohols. In recent years,the synthesis of carbamates has been achieved through the reactionof ureas with alcohols using various catalytic systems. Thus,Chaudhari and co-workers have reported the synthesis of carba-

Qin and co-workers have reported269 the synthesis of phenylmethyl carbamates 6 through the reaction of aniline 4, urea 194(RH) and methanol 5 using various kinds of catalysts (Scheme165). They have realised that KNO3modied zeolite HY gave the

3.8.6. Carbamate synthesis from carbonyl compounds. Tomkinsonand co-workers have rst reported the synthesis of a-carbamates197 through the reaction of various kinds of carbonyl compounds196 with N-methyl-O-carbamoyl-hydroxylamine hydrochlorides

270