Embed Size (px)
Citation preview
77
Z. Zhu et al. Short ReviewSyn Open
SYNOPEN2 5 0 9 - 9 3 9 6Georg Thieme Verlag Stuttgart · New York2019, 3, 77–90short reviewen
Catalytic Enantioselective Approaches to the oxa-Pictet–Spengler Cyclization and Other 3,6-Dihydropyran-Forming ReactionsZhengbo Zhua Alafate Adilia Chenfei Zhaob 0000-0003-3960-3047 Daniel Seidel*a 0000-0001-6725-111X
a Center for Heterocyclic Compounds, Department of Chemis-try, University of Florida, Gainesville, Florida 32611, [email protected]
b Department of Chemistry, University of California–Berkeley; Materials Sciences Division, Lawrence Berkeley National Labo-ratory; Kavli Energy NanoSciences Institute at Berkeley; Berke-ley Global Science Institute, Berkeley, California 94720, USA
O
HO
OH
HO
R
NH
O
RNH
OH
RCHO
Brønsted acidcatalysis
Dual anion-bindingiminium catalysis
up to99% ee
up to 95% ee
Received: 24.08.2019Accepted after revision: 04.09.2019Published online: 25.09.2019DOI: 10.1055/s-0039-1690686; Art ID: so-2019-d0023-r
License terms:
© 2019. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Abstract This Short Review provides an analysis of the state-of-the-artin catalytic enantioselective oxa-Pictet–Spengler cyclizations. Also dis-cussed are other catalytic reactions providing access to enantio-enriched isochromans and tetrahydropyrano[3,4-b]indoles. Context isprovided and remaining challenges are highlighted.
Key words oxa-Pictet–Spengler cyclization, isochromans, tetrahydro-pyrano[3,4-b]indoles, oxocarbenium ions, asymmetric catalysis, ionpairing
Among compounds containing a 3,6-dihydropyran core,isochromans and tetrahydropyrano[3,4-b]indoles have cap-tured particular interest in the synthetic and medicinalchemistry communities. A small selection of compoundscontaining these core frameworks is shown in Figure 1. Theisochroman heterocycle is a ubiquitous component of natu-ral products often possessing intriguing bioactivities, suchas ilexisochromane,1 penicisochroman B,2 and blapsin B.3Synthetic isochromans include the antiapoptotic agent ISO-094 and the 5-HT1D agonist PNU-109291.5 Examples of bio-active tetrahydropyrano[3,4-b]indoles are the anti-inflam-matory agent etodolac,6 the potent analgesic agent pe-medolac,7 and the non-nucleoside inhibitor of hepatitis Cvirus HCV-371.8 The perhaps most desirable way to accessisochromans and tetrahydropyrano[3,4-b]indoles in astereocontrolled fashion is by means of the oxa-Pictet–Spengler cyclization; a process in which an oxocarbeniumion intermediate undergoes ring-closure onto a pendent
aryl substituent.9 In this Short Review, we provide exam-ples of asymmetric oxa-Pictet–Spengler cyclizations thatare under substrate control, discuss all known catalytic en-antioselective variants of the oxa-Pictet–Spengler cycliza-tion,10 and provide an overview of other catalytic enanti-oselective reactions that lead to isochromans and tetrahy-dropyrano[3,4-b]indoles. In addition, we outline remainingchallenges in this area.
Figure 1 Examples of naturally occurring and artificial bioactive iso-chromans and tetrahydropyrano[3,4-b]indoles
The Pictet–Spengler reaction was discovered in 1911and involves the HCl-promoted condensation of -phenethylamine and formaldehyde dimethyl acetal to form1,2,3,4-tetrahydroisoquinoline (Scheme 1).11 The definition
O
HO
HO
MeO2C
OHC
Me
O
Me
ilexisochromane
(+)-penicisochroman B
O
HO
HO
HO
OHblapsin B
O
O
O
Oi-Pr
ISO-09
O
NH
O
Me
N
N
OMe
PNU-109291
NH
O
EtEtCO2H
(S)-etodolac
NH
O
n-PrMeCO2H
NH
O
EtCO2H
CN
HCV-371
Bn
pemedolac
OMeO
O
i-Pr
SynOpen 2019, 3, 77–90Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany
78
Z. Zhu et al. Short ReviewSyn Open
of the Pictet–Spengler reaction was later expanded toinclude cyclizations of imines or iminium ions possessing acovalently linked aryl group that undergoes substitutionupon ring-closure.12 While the apparently first example ofan oxa-Pictet–Spengler reaction dates back to 1935,13 whenthe synthesis of isochroman from chloroether 1 was dis-closed in a patent by Buschmann and Michel (Scheme 1),the term oxa-Pictet–Spengler cyclization was coined by
Wünsch and Zott only in 1992.14 While it was found that -phenylethanol can condense directly with formaldehyde orparaformaldehyde in the presence of aqueous HCl to formisochroman without the need to first isolate 1, this ap-proach inadvertently leads to side products containingchloromethyl groups on the phenyl ring (not shown).14,15 Asoutlined in Scheme 1, the general mechanism of the oxa-Pictet–Spengler reaction involves the formation of an oxo-
Biographical Sketches
Zhengbo Zhu was born andraised in Jiangxi, China. Heearned his B.Sc. degree in theDepartment of Chemistry andChemical Engineering at Nan-jing University working with
Prof. Chengjian Zhu. In 2014, hemoved to Rutgers University forhis graduate studies, joining thegroup of Prof. Daniel Seidel. InAugust of 2017, he moved withthe Seidel group to the Universi-
ty of Florida. His research focus-es on asymmetric Brønsted acidcatalysis and redox-neutral -C–Hbond functionalization of cyclicamines.
Alafate Adili was born andraised in Xinjiang, China. Heearned his B.Sc. degree in theDepartment of Chemistry at theUniversity of Science and Tech-
nology of China (USTC) workingwith Prof. Liu-Zhu Gong. In2016, he started his Ph.D. re-search at Rutgers University un-der the direction of Prof. Daniel
Seidel. In August of 2017, hemoved with the Seidel group tothe University of Florida. His re-search focuses on asymmetriccatalysis.
Chenfei Zhao was born in Chi-na in 1989 and received hisB.Sc. at Wuhan University ofTechnology in 2012. He ob-
tained his Ph.D. (2017) fromRutgers University working oncooperative catalysis under thedirection of Prof. Daniel Seidel.
He is currently a postdoctoralresearcher in Prof. Omar M.Yaghi’s lab at UC Berkeley work-ing on reticular chemistry.
Daniel Seidel studied chemis-try at the Friedrich-Schiller-Uni-versität Jena, Germany, and atthe University of Texas at Austin(Diplom 1998). He performedhis graduate studies in the labo-ratory of Prof. Jonathan L.
Sessler, obtaining his Ph.D. in2002. From 2002 to 2005, hewas an Ernst Schering Postdoc-toral Fellow in the group of Prof.David A. Evans at Harvard Uni-versity. He started his indepen-dent career at Rutgers
University in 2005 and was pro-moted to Associate Professor in2011 and Full Professor in 2014.In the summer of 2017, his re-search group moved to the Uni-versity of Florida.
SynOpen 2019, 3, 77–90
79
Z. Zhu et al. Short ReviewSyn Open
carbenium ion, followed by ring closure and subsequentdeprotonation/rearomatization. Both the Pictet–Spenglercyclization and the oxa-Pictet–Spengler cyclization can beviewed as variants of an intramolecular Friedel–Crafts al-kylation.16 In addition, the oxa-Pictet–Spengler cyclizationis mechanistically related to certain types of the Prins reac-tion.17
Scheme 1 Original reports on the Pictet–Spengler reaction and its ox-ygen analogue, along with its general mechanism
For the majority of the history of the oxa-Pictet–Spenglerreaction, asymmetric variants were limited to cyclizationsof enantioenriched starting materials.9 Several illustrativeexamples of such diastereoselective oxa-Pictet–Spengler cy-clizations are provided in Scheme 2. A chiral auxiliary basedapproach was reported by Costa et al., utilizing -ketoester3 derived from (–)--pinene.18 Condensation of tryptophol(2)19 with -ketoester 3 is facilitated by SnCl4, resulting inthe formation of product 4 with excellent diastereoselectiv-ity. Interestingly, the use of BF3 etherate in place of SnCl4provides a 1:1 mixture of product diastereomers. The ratioof the starting materials and the amount of the Lewis acidare not specified in this report. Also, the absolute configura-tion of product 4 remains unknown. A highly diastereose-lective oxa-Pictet–Spengler cyclization was reported byFernandes and Brückner in the course of a synthesis of (+)-kalafungin.20 Exposure of 5 to two equivalents of acetalde-hyde dimethyl acetal and excess BF3 etherate providesproduct 6 as a single diastereomer in excellent yield. As partof their synthesis of (–)-platensimycin, Eey and Lear ex-plored the conversion of 7 into 8 via an interesting type ofoxa-Pictet–Spengler cyclization under a variety of condi-tions.21 Although the reaction can be facilitated with a largeexcess of SnCl4 (8 equiv), the optimal conditions involve ex-posure of 7 to a catalytic amount of Bi(OTf)3 (5 mol%) in thepresence of lithium perchlorate (3 equiv) and molecular
sieves in dichloromethane at room temperature, allowingfor the isolation of polycyclic product 8 in excellent yield. Arecent example of a Brønsted acid catalyzed diastereoselec-tive oxa-Pictet–Spengler cyclization was reported by Da andco-workers.22 Tryptophol derivative 9, derived from the en-antioselective CBS reduction of the corresponding ketone,engages benzaldehyde dimethyl acetal in the presence of acatalytic amount of trifluoroacetic acid to furnish tetrahy-dropyrano[3,4-b]indole 10 in excellent yield and dr. Consis-tent with the expected mechanism of this transformation,the ee of product 10 matches that of the starting material 9.
Scheme 2 Examples of diastereoselective oxa-Pictet–Spengler reac-tions with optically active starting materials
The first documented efforts toward developing a cata-lytic enantioselective variant of the oxa-Pictet–Spengler re-action were disclosed by Doyle in 2008.23 Evaluation of anumber of (thio)urea catalysts in direct condensations oftryptophol with a range of aldehydes and ketones, either inthe absence or presence of various Brønsted and Lewis acidadditives and dehydrating agents, was reported to lead totetrahydropyrano[3,4-b]indole products with low levels ofenantioinduction (<15% ee, not shown). Significant increas-es in reactivity and appreciable levels of enantioselectivityare observed with tryptophol-derived mixed acetoxy-
NH2MeO OMe
HCl (concd)
NH
(1.6 equiv) THIQ, 36%
+
Synthesis of 1,2,3,4-tetrahydroisoquinoline (THIQ) by Pictet and Spengler (1911)11
Synthesis of isochroman by Buschmann and Michel (1935)13
O
HCl (concd, 1 equiv)
Oisochroman, 64%
Cl1
oxocarbenium intermediate
OCl
ring-closure
O
ClH
–HCl deprotonation/rearomatization
heat, 5–6 h
20–40 °C, 2 h
NH
O
PhNH
OH
Ph Ph
9, 92% ee
PhCH(OMe)2 (2.5 equiv)TFA (20 mol%)
10, 83%, 92% eedr >20:1
H3CCH(OMe)2 (2 equiv)BF3•Et2O (3 equiv)
Bi(OTf)3 (5 mol%)LiClO4 (3 equiv)
NH
OH
24, 59%, de >95%
Me Me
OMe
O
O O
Me
NH
O
MeCO2R*
SnCI4, THF, rt
3
OMe OMe
OMe O
OH
O
OMe OMe
OMe O
O
O
Me
5 6, 92%
OBn
OMe
O
Me
OTs
HOOBn
OMe
Me
OTs
O
8, 94%7
*
Et2O/THF (4:1), rt, 12 h
4Å MS, CH2Cl2, rt, 3.5 h
CH2Cl2, rt, 48 h
SynOpen 2019, 3, 77–90
80
Z. Zhu et al. Short ReviewSyn Open
acetals such as 11; precursors that enable the formation ofthe requisite oxocarbenium ion intermediates under milderconditions (Scheme 3). Exposure of 11 to trimethylsilylchloride in the presence of thiourea catalyst 13 furnishesproduct 12 in excellent yield and encouraging 49% ee (abso-lute configuration not established). Higher levels of enanti-oselectivity are obtained with N-MOM protected tryptop-hol acetals 14 (Scheme 4). Reactions of acetals 14, per-formed under identical conditions, provide thecorresponding products 15 with up to 81% ee (absolute con-figuration of products not established). Promising prelimi-nary results for catalytic enantioselective oxa-Pictet–Spen-gler cyclizations were also obtained with acetoxy-acetalsderived from a number of -heteroaryl ethanols (Scheme5). Regarding the mechanism of these transformations, thehydrogen-bond donor24 thiourea catalyst most likely inter-acts with chloride via anion-binding,25 forming a chiral ionpair with the oxocarbenium ion.
Scheme 3 Thiourea-catalyzed enantioselective oxa-Pictet–Spengler cyclization with mixed acetals derived from tryptophol
Scheme 4 Thiourea-catalyzed enantioselective oxa-Pictet–Spengler cyclization with N-MOM protected tryptophol acetals, selected scope
Another early example of a catalytic enantioselectiveoxa-Pictet–Spengler cyclization was reported by Scheidtand co-workers in 2013 (Scheme 6).26 Chiral phosphoricacid catalyst 19 is capable of converting preformed enol
ether 17 into the corresponding cyclization product 18 witha moderate level of enantiocontrol (absolute configurationnot established). Here, the intermediate oxocarbenium ionis generated by protonation of enol ether 17 by the chiralBrønsted acid 19.27
Scheme 6 Brønsted acid catalyzed enantioselective oxa-Pictet–Spengler cyclization with a preformed enol ether
Shortly thereafter, Nielsen and co-workers reported arelated approach in which enol ethers are generated in situfrom allyl ethers via a ruthenium catalyzed isomerizationprocess (Scheme 7).28 Application of this strategy to allylether 20, in the presence of chiral imidodiphosphoric acid22, furnishes product 21 in good yield. While the enantio-selectivity achieved in this reaction is only moderate (abso-lute configuration not established), this is the only examplethus far that generates a tetrasubstituted stereogenic centerin the course of an oxa-Pictet–Spengler cyclization. The E/Zselectivity of the initial isomerization step is unknown.
NH
S
NH
O
N
Me
Me
t-Bu
CF3
CF3
NH
O
n-C5H11
catalyst 13 (20 mol%)TMSCl (0.7 equiv)
TBME (0.2 M)
–30 °C, 24 h
13
12, 98%, 49% ee
*NH
O
OAc
n-C5H11
(±)-11
N
O
R'
catalyst 13 (20 mol%)TMSCl (0.7 equiv)
TBME (0.2 M)
–30 °C, 3 d
15
*N
O
OAc
R'
MOM MOM
R
14
N
O
n-C5H11
*N
O
n-C5H11
*
15a, 88%, 73% ee 15b, 95%, 69% ee 15c, 89%, 81% ee
MeO
MOMMOM
R
N
O
n-C5H11
*F
MOM
Scheme 5 Thiourea-catalyzed enantioselective oxa-Pictet–Spengler cyclizations involving various heterocycles
NH
S
NH
O
N
Me
Me
t-Bu
CF3
CF3
X
O
catalyst 16 (20 mol%)TMSCl (0.7 equiv)
TBME (0.2 M)
–30 °C, 18 h
16
*X
O
OAc
n-C5H11
S
O*
N
O*
SEM
S
O*
O
O*
20% conv., 16% ee 20% conv., 35% ee
24%, 20% ee
35% conv., 55% een-C5H11 n-C5H11 n-C5H11
n-C5H11
n-C5H11
Ar
Ar
O
OP
OH
O
19 [Ar = 3,5-(CF3)2-C6H3]
N
Ph
O
Mecatalyst 19 (10 mol%)
N
Ph
O
Et
*
17 18, 75%, 60% ee
PhMe (0.1 M), 4 Å MS23 °C, 3 d
SynOpen 2019, 3, 77–90
81
Z. Zhu et al. Short ReviewSyn Open
Scheme 7 Dually catalyzed enantioselective oxa-Pictet–Spengler cy-clization of an allyl ether
The first highly enantioselective catalytic oxa-Pictet–Spengler cyclization was reported by our group in 2016(Scheme 8).29 In the presence of thiourea catalyst 24 andammonium salt catalyst 25, tryptophol (2) undergoes anoxa-Pictet–Spengler reaction with benzaldehyde to formproduct 23a in excellent yield and ee. Substituted benzalde-hydes also participate in this reaction. While para-substi-tuted benzaldehydes provide products with excellent ee,meta-substitution leads to a slight drop-off in enantioselec-tivity, and ortho-substitution results in a significant erosionof ee (e.g., product 23f). Substitution of the indole ring iscompatible with the catalytic system, whereas aliphatic al-dehydes are not viable reaction partners. Mechanistically,this method is based on a dual catalysis strategy that avoidsthe need for strongly acidic conditions commonly requiredfor accessing oxocarbenium ions via direct condensation ofaldehydes and alcohols. The ammonium salt catalyst 25 isthought to first engage the aldehyde to form an iminiumion30 that then reacts with tryptophol, ultimately resultingin the formation of an oxocarbenium ion that likely inter-acts with the catalyst via anion-binding. A plausible transi-tion state for the key C–C bond-forming step is shown inScheme 8. This model is supported by the following obser-vations: (1) there is a strong dependence on the nature ofthe anion with regard to reactivity and product ee; (2) Theenantioselectivity of the reaction is solely dependent oncatalyst 24 (e.g., almost identical results are obtained withthe enantiomer of 25 or racemic 25), and (3) The reactionwith N-methyl tryptophol provides racemic product (e.g.,product 23k), indicating an important interaction of the in-dole N-H with a hydrogen-bond acceptor site on the cata-lyst (e.g., the S-atom of the electron-rich thiourea moiety)in the enantio-determining step of the reaction. Interest-ingly, catalyst 25 can be replaced with HCl to provide theproduct with nearly identical ee but in a significantly moresluggish reaction.
Scheme 8 Dually catalyzed enantioselective oxa-Pictet–Spengler reac-tions of tryptophols with aldehydes
Nearly simultaneously to our report, the List group re-ported a distinct strategy for realizing highly enantioselec-tive oxa-Pictet–Spengler cyclizations (Scheme 9).31 Nitratedimidodiphosphoric acid catalyst 28 was found to efficientlycatalyze reactions of hydroxy-substituted -phenylethanolswith aldehydes. Catalyst 28 is significantly more active thanthe analogous imidodiphosphoric acid catalyst lacking thetwo nitro groups. The corresponding BINOL-based phos-phoric acid 29 is also a competent catalyst but affords theproducts with significantly lower levels of enantioselectivi-ty. Catalyst 28 provides products 27 with excellent ee val-ues while accommodating a range of aromatic and aliphaticaldehydes, with the latter requiring elevated reaction
NH
O
20, racemic 21, 75%, 47% ee
NH
O
Me Et
*
Ar
Ar
O
OP P
O
O
Ar
Ar
N
HOO
22 (Ar = 2-i-Pr-5-Me-C6H3)
catalyst 22 (5 mol%)RuHCl(CO)(PPh3)3 (5 mol%)
PhMe, reflux, 1 hNH
O
PhNH
OH
23a, 90%, 91% ee
NH HN
S
HN
S
R2NNH2
CO2Me
ClCF3
24 (R = cyclooctyl)
N
H
H
NN
SAr
HH
N
S
N
R
R
H
H
O
H H
Stereochemical model
2
25
catalyst 24 (10 mol%)catalyst 25 (10 mol%)
PhCHO (1.2 equiv), PhMe (0.05 M)
4 Å MS, –30 °C, 48 h
Selected scope:
NH
O
Br
23b, 91%93% ee
NH
O
23c, 90%95% ee Me
NH
O
23d, 73%82% ee
NH
O
23e, 82%86% ee
Cl
OMe
NH
O
Me
23f, 91%48% ee
NH
O
23g, 86%88% ee
NH
O
Ph
23j, 89%94% ee
Cl
NH
O
Ph23i, 91%92% ee
Br
NH
O
Ph
Me
23h, 75%81% ee
NMe
O
Ph
23k, 62% (rt, 24 h)racemic
Cl
SynOpen 2019, 3, 77–90
82
Z. Zhu et al. Short ReviewSyn Open
temperatures (50 °C). An additional methoxy group on 26ais also tolerated. The proposed transition state for the C–Cbond-forming step involves a critical hydrogen-bonding in-teraction of the catalyst anion with the phenol O-H moiety,as elucidated by DFT calculations. An alternate transitionstate in which ring-closure occurs in ortho- rather thanpara-position of the phenol O-H moiety was calculated tobe 6.3 kcal/mol higher in free energy (not shown). Consis-tent with these calculations, these regioisomers are not ob-served.
Scheme 9 Imidodiphosphoric acid catalyzed enantioselective oxa-Pictet–Spengler reactions of hydroxy-substituted -phenylethanols with aldehydes
Interesting observations were made in the course of theList study, outlining remaining challenges (Scheme 10).Consistent with the calculated transition state depicted inScheme 9, the presence of a 3-hydroxy substituent on the-phenylethanol is a strict requirement. In the presence of
catalyst 29, -phenylethanols 26b–d react with aldehydesto provide symmetrical acetals 30 as the only products. Onthe other hand, the 2-hydroxy substrate 31 undergoes for-mation of seven-membered cyclic acetal 32, whereas 33 af-fords complex mixtures in reactions with aldehydes.
Scheme 10 Current limitations in oxa-Pictet–Spengler reactions with -phenylethanols
In 2018, Scheidt and co-workers published an alternatestrategy to access tetrahydropyrano[3,4-b]indoles in highlyenantioenriched form.32 A combination of chiral phosphor-ic acid catalyst 36 and achiral urea catalyst 37 facilitates cy-clizations of tryptophol-derived enol ethers such as 34a togenerate oxa-Pictet–Spengler products with high levels ofenantioselectivity (e.g., 35a). The presence of a urea-typeprotecting group on the tryptophol nitrogen is a crucial de-sign element of this approach (vide infra). While chiralphosphoric acid 36 is capable of catalyzing the reaction inthe absence of urea 37, reaction rates are dramatically re-tarded (incomplete reaction after 18 h vs. complete reactionwithin 15 min) and afford product 35a in only 36% ee (notshown). Regarding the scope of this transformation, substi-tution of different indole ring positions is readily accommo-dated. While most products contain a gem-dimethyl groupadjacent to the tetrahydropyrano oxygen atom, productslacking these substituents are also obtained with excellentee values. Interestingly, this study contains the only exam-ple thus far reported in which a seven-membered ring isconstructed enantioselectively in the course of an oxa-Pic-tet–Spengler cyclization, albeit in only 32% ee (product 35i).As an application of their method, the authors reported afacile synthesis of coixspirolactam C from oxa-Pictet–
O
HO
OH
HO
Ph
27a, 91%, 96% ee
Ar
Ar
O
OP P
O
O
Ar
Ar
N
HOO
O2N
O2N
28 (Ar = 2,4,6-Et3-C6H2)
catalyst 28 (10 mol%)PhCHO (1.2 equiv), MTBE (0.2 M)
5 Å MS, rt, 72 h
26a
O
HO
MeO
Ph
27h, 98%, 97% ee
Selected scope:
O
HO
MeO
27i, 92%, 99% ee
Me
Me
O
HO
27b, 81%, 95% ee
Ph
O
HO
27c, 82%, 96% eeMe
O
HO
Br
O
HO
Br
O
HO
OMe
O
HO
27d, 87%, 99% ee
27e, 75%, 98% ee 27g, 93%, 96% ee27f, 73%, 90% ee
Calculated TS
O
O
H
H
O
OP
NPO
O
O
O
O
R
OH
R
R''
27 (not observed)Ar
Ar
O
OP
OH
O
29 (Ar = 2,4,6-Et3-C6H2)
catalyst 29R''CHO
26b (R = R' = H)26c (R = OMe, R' = H)26d (R = R' = OMe)
R'O
R
R'
R''
O
R'
R30
R'
OH
catalyst 29RCHO
OH
catalyst 29RCHO
OH
HO
complex reaction mixtures
O
OR
31 32
33
SynOpen 2019, 3, 77–90
83
Z. Zhu et al. Short ReviewSyn Open
Spengler product 35h. Regarding the mechanism of thistransformation, it was proposed that a network of hydro-gen-bonding interactions is responsible for achieving highlevels of reactivity and enantiocontrol (see proposed TS inScheme 11). Specifically, the thiourea catalyst is thought tobind to the chiral phosphate anion via dual hydrogen bond-ing while engaging in an additional hydrogen-bonding in-teraction with the carbonyl group of the protonated sub-strate.
Scheme 11 Dually catalyzed enantioselective oxa-Pictet–Spengler re-actions of tryptophol-derived enol ethers
While not aiming to be complete, the following sectionprovides an overview of catalytic enantioselective reactionsthat lead to oxa-Pictet–Spengler type products by alternatepathways also involving the intermediacy of oxocarbeniumions. As exemplified in the synthesis of enantioenrichedisochromans, nucleophilic additions to cyclic oxocarbeniumions provide an alternative to the oxa-Pictet–Spengler cy-clization (Figure 2). While cyclic isochroman-type oxocar-benium ions are more stable than their corresponding acy-clic counterparts by virtue of conjugation with the fusedand necessarily coplanar aryl ring, they offer an expandedarray of opportunities for designing enantioselective vari-ants. To render oxa-Pictet–Spengler cyclizations catalyticand enantioselective, the anion X– has to be homochiral(e.g., conjugate base of a chiral Brønsted acid catalyst). Al-ternatively, if achiral, X– has to be tightly associated with achiral anion receptor catalyst (or catalyst ensemble) in or-der to facilitate the ring-closure step in an enantioselectivefashion. These modes of enantiocontrol are also available innucleophilic additions to cyclic oxocarbenium ions. In addi-tion, the otherwise achiral nucleophile can be rendered chi-ral by interaction with a chiral catalyst. Nucleophiles can becarbon- or heteroatom-based, enabling the formation ofmonosubstituted isochromans via a reductive process.
Figure 2 Different pathways to enantioenriched isochromans.
A 2008 landmark study by the Jacobsen group accom-plished the first catalytic enantioselective synthesis of 1-substituted isochromans (Scheme 12).33,34 Treatment of iso-chroman-derived acetal 38 with BCl3 results in the in situformation of 1-chloroisochroman (not shown), which isthen converted into product 39a upon treatment with silylketene acetal 41 in the presence of thiourea catalyst 40.Binding of the chloride counter anion of the transient oxo-carbenium ion to thiourea catalyst 40 is thought to form achiral ion pair responsible for controlling the facial selectiv-ity in the silyl ketene acetal addition step. Isochromans con-taining substituents on different positions of the aryl ringand a range of silyl ketene acetals participate in this trans-formation to provide products 39 in good yields and excel-lent ee values.
N
O
Me
MeMe
OArHN
N
O
MeMe
OArHN
Et
35a, 89%, 94% ee34a (Ar = 3,5-(CF3)2-C6H3)
Ar
Ar
O
OP
O
OH
O
NH
NH
Ar Ar
36 [Ar = 3,5-(CF3)2-C6H3]
catalyst 36 (10 mol%)catalyst 37 (10 mol%)
PhMe (0.02 M), –40 °C, 2 h
37 [Ar = 3,5-(CF3)2-C6H3]
Proposed TS
Selected scope:
N
O
MeMe
OArHN
Et
35f, 89%, 60% ee
N
O
MeMe
OArHN
Et
35c, 88%, 94% ee
Cl
N
O
MeMe
OArHN
Et
35e, 93%, 90% ee
MeO
N
OArHN
35i, 64%, 32% ee
O
Et
Me
Me
N
O
MeMe
OArHN
Et
35d, 90%, 92% ee
MeO
N
O
MeMe
OArHN
Et
35b, 73%, 84% ee
F
MeN
O
OArHN
Et
35g, 54%, 96% ee
N
O
OArHN
Me
35h, 76%, 94% ee
O
O
PO
O
O
N
N
Ar
Ar
H
H
NO NH
Ar
O
Et
H
oxa-Pictet-Spenglercyclization
O
XR'
RO
R Nu
X
Nucleophilic addition to cyclic oxocarbenium ion
vs.
SynOpen 2019, 3, 77–90
84
Z. Zhu et al. Short ReviewSyn Open
Scheme 12 Catalytic enantioselective additions of silyl ketene acetals to cyclic oxocarbenium ions
In 2011, Watson and co-workers reported a conceptual-ly different strategy for the catalytic enantioselective addi-tion of nucleophiles to isochroman-derived oxocarbeniumions (Scheme 13).35 Specifically, catalytic enantioselectivealkynylation of acetal 38 with phenylacetylene is achievedwith a Cu(I) complex of bisoxazoline ligand 43. Hünig’s basefacilitates the formation of a chiral Cu acetylide complexthat adds to the oxocarbenium ion derived from acetal 38and TMSOTf. The reaction tolerates substituents on differ-ent positions of the isochroman aryl ring and is applicableto a range of terminal alkynes. Some products are some-what sensitive to oxidative decomposition (e.g., lactone for-mation). This is particularly true for product 42h (the yieldshown corresponds to the product obtained from subse-quent reduction of the alkyne moiety to the correspondingalkane via hydrogenation). An impressive extension of thischemistry was reported in 2015 (Scheme 14).36 A modifiedcatalyst system derived from Pybox ligand 46 enables thesynthesis of highly enantioenriched isochromans 45 from1-substituted isochroman ketals 44. This is a rare example
of a catalytic enantioselective process generating isochro-mans containing challenging tetrasubstituted stereogeniccenters.
Acetals such as 38 are typically obtained from their cor-responding isochromans via an oxidative process. In 2014,the Liu group reported a strategy that obviates the need forpreparing acetals in a separate step (Scheme 15).37,38 Oxo-carbenium ions are accessed in situ by oxidation of isochro-mans with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ). Addition of the aldehyde substrate is facilitated bycatalyst 48 via an enamine mechanism. Reduction of theinitially formed aldehyde products with sodium borohy-dride provides substituted isochromans (e.g., 47a–g) andrelated products with excellent levels of enantioselectivity,albeit with moderate diastereoselectivity. As part of thisstudy, the Liu group achieved the catalytic enantioselectiveaddition of boronic ester 51 to isochroman (Scheme 16).This reaction is facilitated by tartaric-acid-derived catalyst50 and provides product 49 with moderate ee after hydro-genation in situ.39
OO
OMeCO2Me
MeMe
i) BCl3, CH2Cl2, 0 °C to rt
ii) catalyst 40 (10 mol%), silyl ketene acetal 41 (1.5 equiv) TBME, –78 °C, 24 h
NH
S
NH
O
N
t-Bu
CF3
CF3
40
F
(±)-38
39a, 92%, 92% ee
41
Me
Me
OTMS
OMe
O
CO2Me
39b, 87%, 85% ee
O
CO2Me
39c, 71%, 90% ee
Me
O
CO2Me
39d, 70%, 90% ee
F
O
CO2Me
39e, 82%, 87% ee
Me
O
MeO2C
O
MeO2C
Selected scope:
39f, 84%, 94% ee 39g, 85%, 92% ee
ArNH
S
NH
O
N
t-BuR'
R
O
key ion pairCl
Scheme 13 Catalytic enantioselective alkynylation of isochroman-derived oxocarbenium ions
O
O
OMe(±)-38
42a, 89%, 89% ee
MeMe
Cu(MeCN)4PF6 (10 mol%)ligand 43 (12 mol%)TMSOTf (1.2 equiv), i-Pr2NEt (1.3 equiv)
Et2O (0.4 M), –22 °C, 12 h
PhH Ph
(1.1 equiv)
+
43
Selected scope:
O
42b, 83%, 91% ee
Me
O
42c, 73%, 85% ee
Cl
O
42d, 77%, 87% ee
CF3
O
42e, 64%, 67% ee
O
42f, 73%, 94% ee
Ph
O
42g, 88%, 87% ee
Ph
Me
O
42h, 50%, 85% ee
3-MeC6H4
MeO
MeO
N
OO
N
Bn Bn
SynOpen 2019, 3, 77–90
85
Z. Zhu et al. Short ReviewSyn Open
Scheme 15 Catalytic enantioselective addition of enolizable aldehydes to isochromans
Scheme 16 Catalytic enantioselective addition of a boronic ester to isochroman
In 2017, the Liu group reported an interesting redox de-racemization strategy that provides highly enantioenrichedisochromans 52 (Scheme 17).40 Racemic starting materialssuch as (±)-52a are oxidized in situ by DDQ to the corre-sponding oxocarbenium ions, which initially form acetals inthe presence of methanol. The subsequent reduction stepwith Hantzsch ester 54 is rendered enantioselective by imi-dodiphosphoric acid catalyst 53. In a subsequent study,similar products were obtained by reduction of preformedracemic acetals (not shown).41 Products 52a could poten-tially be obtained more directly via an oxa-Pictet–Spenglercyclization from the corresponding -phenylethanols. How-ever, current limitations make this an elusive goal (see dis-cussion centered around Scheme 10). The Liu group furtherapplied their redox deracemization strategy to the synthe-sis of highly enantioenriched tetrahydropyrano[3,4-b]in-doles, as highlighted in Scheme 18.42 For these substrates,SPINOL-derived phosphoric acid 55 and Hantzsch ester 56provide optimal results. Tetrahydropyrano[3,4-b]indolescontaining an aryl substituent are typically obtained in ex-cellent yields and ee values. Unfortunately, just like the pre-viously discussed oxa-Pictet–Spengler reaction of tryptop-hol is incompatible with aliphatic aldehydes (see Scheme8), the deracemization process does not tolerate 1-alkylsubstituents as these substrates fail to undergo oxidationunder the standard reaction conditions.
Another strategy for synthesizing enantioenriched iso-chromans, different from everything discussed thus far, in-volves reactions in which the enantio-determining step isC–O bond formation. Scheme 19 highlights seminal work inthis area, published by Kitamura and co-workers in 2011.43
Ruthenium complex 59, at a catalyst loading of only 0.1mol%, facilitates intramolecular dehydrative O-allylation of57 to furnish 1-vinyl isochroman 58a in excellent yield andee in a sequence that proceeds via the intermediacy of a Ru--allyl species.
A mechanistically distinct approach published by Whiteand co-workers in 2016 accomplishes the synthesis of relat-ed isochroman products by intramolecular catalyticenantioselective allylic C–H oxidation (Scheme 20).44 A
Scheme 14 Formation of tetrasubstituted stereogenic centers via cat-alytic enantioselective alkynylation of isochroman-derived oxocarbeni-um ions
O
OMe
(±)-44
45a, 92%, 78% ee
CuSPh (10 mol%), ligand 46 (12 mol%)MTBD (1.55 equiv), BF3•OEt2 (2 equiv)
Et2O (0.15 M), 4 °C, 48 h
H Ph
(1.2 equiv)
+
46
Selected scope:
N
N
OO
N
Ph Ph
Ph O
Ph
Ph
N
N
N
Me
MTBD
45b, 66%, 70% ee
O
PhMe
45c, 86%, 96% ee
O
Ph
MeO
45d, 71%, 87% ee
O
Ph
S
45e, 87%, 97% ee
O
CN
OMe
O
SiPhMe2
45f, 53%, 81% ee
O
45g, 80%, 93% ee
NPhth
O
47a, 69%, 96% eedr = 72:28
48Selected scope:
O
n-PrHO HH
i) DDQ (1 equiv), H2O (1.1 equiv), C2H4Cl2 then catalyst 48•TFA (20 mol%) aldehyde (3 equiv) LiOTf (1 equiv), MeNO2, 0 °C, 30–48 h
ii) NaBH4, MeOH
N
NH
O Me
Me
MeBn
O
RHO HH
47b (R = Me), 66%, 93% ee, dr = 69:3147c (R = Bn), 79%, 96% ee, dr = 73:2747d (R = PMB), 73%, 95% ee, dr = 75:2547e (R = C4H8OBn), 63%, 90% ee, dr = 71:2947f (R = C4H8OTBS), 65%, 94% ee, dr = 70:30
O
n-PrHO HH
MeO
MeOS
n-PrHO HH
n-PrHO HH
O PMP OMe
n-PrHO HH
47jnot formed
47g, 92%, 96% eedr = 79:21
47h, 85%, 90% eedr = 67:33
47i, 55%, 96% eedr = 63:37
O
49, 62%, 61% ee
50
O
i) DDQ, H2O, C2H4Cl2 then catalyst 50 (30 mol%) 51 (1.5 equiv), rt, 24 h
ii) H2, Pd/C, MeOH
Ph
51
HO
O
O
N
Bn
Bn
OH
OH
BPh
OEt
EtO
SynOpen 2019, 3, 77–90
86
Z. Zhu et al. Short ReviewSyn Open
complex derived from palladium acetate and ligand 61, inthe presence of diphenylphosphinic acid, catalyzes thetransformation of -arylethanols such as 60 to 1-vinyl iso-chromans 58, and the products are obtained with excellentlevels of enantioselectivity. 2,6-Dimethylbenzoquinone(2,6-DMBQ) serves as the terminal oxidant in this process.
The catalytic enantioselective synthesis of 1-alkynylisochromans was reported by Nishibayashi and co-workersin 2019 (Scheme 21).45 A Cu(I)-complex derived from Pyboxligand 46 catalyzes the enantioselective intramolecularetherification of propargylic esters (e.g., 62) to provideproducts 63 in good to excellent yields and ee values. Anonlinear relationship exists between the enantiopurity ofligand 46 and product, leading the authors to propose theintermediacy of a dicopper-allenylidene species.
In 2015, Ghorai and co-workers reported a catalytic en-antioselective method for the synthesis of highly enantio-enriched 1-substituted isochromans (Scheme 22).46 Thismethod is based on intramolecular conjugate addition. Re-duction of the aldehyde functionality of ketoaldehydes suchas 64 by pinacolborane (pinBH) provides an alkoxyboronateintermediate that then undergoes conjugate addition toform products 65 with excellent ee values. Reactions arecatalyzed by quinine-derived squaramide-containing bi-functional organocatalyst 66 and exhibit a broad scope.This method also enables the synthesis of isochromans con-taining a substituent in the 3-position. An example is pro-
vided in Scheme 23. Ketoaldehyde 67, a constitutional iso-mer of 64, undergoes reduction followed by intramolecularconjugate addition to provide product 68 in 81% ee.
Scheme 17 Catalytic redox deracemization of isochromans
O
PMP
52a, 90%, 90% ee
DDQ (1.05 equiv), MeOH (3 equiv)then catalyst 53 (5 mol%)
54 (1.4 equiv), Na2CO3 (0.5 equiv)
CH2Cl2/PhMe, 5 Å MS, –10 °C
(±)-52a
Ar
Ar
O
OP P
O
O
Ar
Ar
N
HOO
53 (Ar = 3,5-(CF3)2-C6H3)
O
PMP
NH
MeMe
CO2EtEtO2C
54
Selected scope:
O
52c, 80%, 91% ee
OMe
O
52e, 70%, 73% ee(performed at rt)
Br
MeO
O
52d, 93%, 92% ee
OMe
AcO
AcO
AcO
O
52b, 91%, 90% ee
SMe
Scheme 18 Catalytic redox deracemization of tetrahydropyrano-[3,4-b]indoles
23a, 90%, 95% ee
DDQ (1.1 equiv), EtOH (3 equiv)then catalyst 55 (5 mol%)
56 (1.4 equiv)
CH2Cl2/Et2O, 4 Å MS, 0 °C
(±)-23a
55 (Ar = 9-phenanthryl)
NH
n-Prn-Pr
CO2EtEtO2C
56
Selected scope:
NH
O
PhNH
O
Ph
Ar
Ar
O
OP
O
OH
NH
O
Br
23b, 88%91% ee
NH
O
23c, 91%92% ee Me
NH
O
23e, 80%90% ee
NH
O
23l, 72%90% ee
MeO
NH
O
23m, 86%92% ee
NH
O
23n, 81%80% ee
NH
O
23o, 90%92% ee
Br
23q, racemic(no reaction)
OMeO S
OMe
NH
O
23p, 94%95% ee
MeO
OMe
NH
O
Me
Scheme 19 Synthesis of enantioenriched isochromans via intramolec-ular dehydrative O-allylation
NN N
N
OO O
O
i-Pri-Pr
i-Pri-Pr
Ru
PF6
OH O
58a, 98%, >98% ee
catalyst 59 (0.1 mol%), TsOH (0.1 mol%)
CH2Cl2, reflux, 1 h
57
59
OH
SynOpen 2019, 3, 77–90
87
Z. Zhu et al. Short ReviewSyn Open
Scheme 22 Synthesis of enantioenriched isochromans via intramolec-ular conjugate addition
Scheme 23 Synthesis of enantioenriched 3-substituted isochromans via intramolecular conjugate addition
Another rare example of a catalytic enantioselectiveprocess leading to isochromans containing a substituent inthe 3-position was reported in 2009 (Scheme 24).47 As partof a broader effort directed at preparing a range of structur-ally diverse compounds, Chung and Fu achieved the catalyt-ic enantioselective synthesis of isochroman 70 from ,-alkynyl ester 69. This isomerization reaction is catalyzed bychiral phosphine 71, operating in concert with benzoic acid.
Scheme 20 Synthesis of enantioenriched isochromans via intramolec-ular allylic C–H oxidation
O
58a, 70%, 92% ee
Pd(OAc)2 (10 mol%), ligand 61 (10 mol%)2,6-DMBQ (1.1 equiv), Ph2PO2H (10 mol%)
PhMe (0.15 M), 45 °C, 8–10 h
60
OH
S
N
OPh
O
t-Bu61
O
O
MeMe
2,6-DMBQ
O
58d, 64%, 92% ee
Selected scope:
O
58b, 69%, 92% ee
O
58c, 68%, 93% ee
O
58g, 55%, 92% ee
O
58e, 76%, 93% ee
O
58f, 61%, 91% ee
Me
Me
F
Br
F
Cl
Scheme 21 Synthesis of enantioenriched isochromans via intramolec-ular etherification of propargylic esters
46
N
N
OO
N
Ph Ph
OAc O
63, 89%, 93% ee
CuOTf•1/2 PhH (5 mol%)ligand 46 (10 mol%), K2CO3 (1.2 equiv)
CF3CH2OH (0.04 M), –20 °C, 51 h
(±)-62
OH
O
63d, 65%, 89% ee
Selected scope:
O
63b, 90%, 91% ee
O
63c, 75%, 88% ee
O
63g, 75%, 80% ee
O
63e, 90%, 87% ee
O
63f, 72%, 93% ee
Me
Me
F
MeOF
Me
N
NH
N
OMe
H
NH
O
O
Ar
O
65a, 81%, 92% ee
pinBH ( 3 equiv), catalyst 66 (10 mol%)MeNO2, 0 °C, 2 h
then i-PrOH, 45 °C, 14 h
64
CHO
65e, 68%, 94% ee
Selected scope:
65b, 68%, 89% ee 65d, 81%, 96% ee
65h, 82%, 94% ee65f, 70%, 93% ee 65g, 72%, 93% ee
O
Ph
Ph
O
66 [Ar = 3,5-(CF3)2-C6H3]
O
O
O
O
O
O
OMe
O S
65c, 80%, 96% ee
O
O
Br
O
O
Br
O
O
O
O
O
O
Cl O
O Me
CHOO
68, 56%, 81% ee
pinBH (5 equiv)catalyst 66 (20 mol%)
MeNO2, 0 °C, 2 h
then i-PrOH, 45 °C, 16 h
67
O
Ph
O
Ph
SynOpen 2019, 3, 77–90
88
Z. Zhu et al. Short ReviewSyn Open
Scheme 24 Synthesis of enantioenriched 3-substituted isochromans via phosphine-catalyzed isomerization of ,-alkynyl esters
Examples of catalytic enantioselective reactions thatprovide enantioenriched tetrahydropyrano[3,4-b]indolescontaining substituents in other than the 1-position areshown in Scheme 25 and Scheme 26. In 2011, the Yougroup achieved enantioselective intramolecular Friedel–Crafts alkylation reactions of indolyl enones (e.g., 72), pro-viding products such as 73 with exceptional efficiency(Scheme 25).48 Reactions are catalyzed by chiral N-triflylphosphoramide 74, a catalyst that is remarkably active at–70 °C. In earlier work published in 2009, the same groupshowed that products such as 73 can be obtained by olefincross-metathesis/Friedel–Crafts alkylation cascades using acompatible combination of a Ru catalyst and a chiral phos-phoric acid catalyst (not shown).49
Scheme 25 Synthesis of enantioenriched tetrahydropyrano[3,4-b]-indoles by intramolecular Friedel–Crafts alkylation
Highly enantioenriched tetrahydropyrano[3,4-b]indolescontaining a fused ring and two stereogenic centers (e.g.,76) can be prepared from substrates such as 75, as reportedby Lu and co-workers in 2017.50 This transformation in-volves a Pd(II)-catalyzed aminopalladation/1,4-addition se-quence that is facilitated by chiral bipyridine ligand 77.
As is clear from the transformations discussed in thisShort Review, access to highly enantioenriched isochro-mans and tetrahydropyrano[3,4-b]indoles by means of
asymmetric catalysis has improved dramatically over thepast 10 years, with most advances having emerged only inthe past 5 years. It is also clear that significant challengesremain. Although highly desirable, for instance for a moreefficient synthesis of drug molecules such as etodolac,methods that efficiently install tetrasubstituted stereogeniccenters remain rare and have largely been limited to addi-tions to cyclic oxocarbenium ions (Scheme 14). Thus far,there is only one example with low enantioselectivity inwhich a tetrasubstituted stereogenic center was generatedvia an oxa-Pictet–Spengler cyclization (Scheme 7). Pictet–Spengler cyclizations of tryptophols or -arylethanols withketones or ketone surrogates would provide the most directaccess to isochromans and tetrahydropyrano[3,4-b]indolescontaining a tetrasubstituted stereogenic center in the 1-position. While such reactions are well known in a racemicsense, catalytic enantioselective variants have remainedelusive. In addition, highly enantioselective oxa-Pictet–Spengler reactions of tryptophols have not yet been accom-plished with aliphatic aldehydes, and reactions with -phenylethanols require the presence of a hydroxyl group ina specific position of the aryl ring. All three of the highlyenantioselective oxa-Pictet–Spengler reactions reported todate (Scheme 8, Scheme 9, and Scheme 11) require thepresence of hydrogen-bonding donor or acceptor sites onthe alcohol substrate. However, encouraging findings suchas those summarized in Scheme 6 suggest that such reac-tions could potentially be rendered highly enantioselectivein the absence of obvious directing groups. Overall, there iscause for optimism that many of these limitations will beaddressed in the not-too-distant future. We look forward tolearning about new advances and hope that this Short Re-view will motivate others to tackle the remaining challenges.
Funding Information
This material is based upon work supported by the National ScienceFoundation under grant CHE–1856613.National Science Foundation (CHE–1856613)
O
70, 82%, 94% ee
catalyst 71 (10 mol%)PhCO2H (50 mol%)
THF, 55 °C, 48 h
69
CO2Et
OH
CO2Et
P Ph
71
73, 99%, 98% ee
catalyst 74 (5 mol%)
PhMe, –70 °C, 24 h
72
N
O
N
O
Ar
Ar
O
OP
NH
O
74 (Ar = 9-anthryl)
Tf
BrBr
Ph
O
Me Me
Ph
O
Scheme 26 Synthesis of enantioenriched tetrahydropyrano[3,4-b]-indoles by a Pd-catalyzed cascade reaction
76, 90%, 95% ee75
N
O
77
Ts
O
EtH
O
Et O
NHTs Pd(OAc)2 (5 mol%)ligand 77 (10 mol%)
DMF/H2O/HOAc = 10:1:1, 50 °C
N
N
O
O
Me
Me
SynOpen 2019, 3, 77–90
89
Z. Zhu et al. Short ReviewSyn Open
References and Notes
(1) Zhou, Y. B.; Wang, J.-H.; Li, X. M.; Fu, X. C.; Yan, Z.; Zeng, Y. M.;Li, X. J. Asian Nat. Prod. Res. 2008, 10, 827.
(2) (a) Trisuwan, K.; Rukachaisirikul, V.; Sukpondma, Y.;Phongpaichit, S.; Preedanon, S.; Sakayaroj, J. Tetrahedron 2010,66, 4484. (b) Kuramochi, K.; Tsubaki, K.; Kuriyama, I.;Mizushina, Y.; Yoshida, H.; Takeuchi, T.; Kamisuki, S.; Sugawara,F.; Kobayashi, S. J. Nat. Prod. 2013, 76, 1737.
(3) Yan, Y.-M.; Dai, H.-Q.; Du, Y.; Schneider, B.; Guo, H.; Li, D.-P.;Zhang, L.-X.; Fu, H.; Dong, X.-P.; Cheng, Y.-X. Bioorg. Med. Chem.Lett. 2012, 22, 4179.
(4) Zhang, L.; Zhu, X.; Zhao, B.; Zhao, J.; Zhang, Y.; Zhang, S.; Miao, J.Vasc. Pharmacol. 2008, 48, 63.
(5) Ennis, M. D.; Ghazal, N. B.; Hoffman, R. L.; Smith, M. W.;Schlachter, S. K.; Lawson, C. F.; Im, W. B.; Pregenzer, J. F.;Svensson, K. A.; Lewis, R. A.; Hall, E. D.; Sutter, D. M.; Harris, L.T.; McCall, R. B. J. Med. Chem. 1998, 41, 2180.
(6) (a) Demerson, C. A.; Humber, L. G.; Philipp, A. H.; Martel, R. R. J.Med. Chem. 1976, 19, 391. (b) Brenna, E.; Fuganti, C.; Fuganti, D.;Grasselli, P.; Malpezzi, L.; Pedrocchi-Fantoni, G. Tetrahedron1997, 53, 17769.
(7) Katz, A. H.; Demerson, C. A.; Shaw, C. C.; Asselin, A. A.; Humber,L. G.; Conway, K. M.; Gavin, G.; Guinosso, C.; Jensen, N. P. J. Med.Chem. 1988, 31, 1244.
(8) Howe, A. Y. M.; Bloom, J.; Baldick, C. J.; Benetatos, C. A.; Cheng,H.; Christensen, J. S.; Chunduru, S. K.; Coburn, G. A.; Feld, B.;Gopalsamy, A.; Gorczyca, W. P.; Herrmann, S.; Johann, S.; Jiang,X.; Kimberland, M. L.; Krisnamurthy, G.; Olson, M.; Orlowski,M.; Swanberg, S.; Thompson, I.; Thorn, M.; Del Vecchio, A.;Young, D. C.; van Zeijl, M.; Ellingboe, J. W.; Upeslacis, J.; Collett,M.; Mansour, T. S.; O’Connell, J. F. Antimicrob. Agents Chemother.2004, 48, 4813.
(9) For reviews on the oxa-Pictet–Spengler reaction, see: (a) Larghi,E. L.; Kaufman, T. S. Synthesis 2006, 187. (b) Larghi, E. L.;Kaufman, T. S. Eur. J. Org. Chem. 2011, 5195. (c) Moyano, A.;Rios, R. Chem. Rev. 2011, 111, 4703.
(10) For a very brief summary of this topic (in Japanese), see:Kawato, Y. J. Synth. Org. Chem. Jpn. 2017, 75, 673.
(11) Pictet, A.; Spengler, T. Ber. Dtsch. Chem. Ges. 1911, 44, 2030.(12) Selected reviews on the Pictet–Spengler reaction: (a) Cox, E. D.;
Cook, J. M. Chem. Rev. 1995, 95, 1797. (b) Youn, S. W. Org. Prep.Proced. Int. 2006, 38, 505. (c) Lorenz, M.; Van Linn, M. L.; Cook, J.M. Curr. Org. Synth. 2010, 7, 189. (d) Stockigt, J.; Antonchick, A.P.; Wu, F. R.; Waldmann, H. Angew. Chem. Int. Ed. 2011, 50, 8538.(e) Glinsky-Olivier, N.; Guinchard, X. Synthesis 2017, 49, 2605.(f) Rao, R. N.; Maiti, B.; Chanda, K. ACS Comb. Sci. 2017, 19, 199.
(13) (a) Buschmann, H.; Michel, R. German Patent 614461, 1935.(b) Buschmann, H.; Michel, R. German Patent 617646, 1935.
(14) Wünsch, B.; Zott, M. Liebigs Ann. Chem. 1992, 39.(15) For an early review on the chemistry of isochromans, see:
Markaryan, E. A.; Samodurova, A. G. Russ. Chem. Rev. 1989, 58,479.
(16) Zeng, M.; You, S.-L. Synlett 2010, 1289.(17) Liu, L.; Kaib, P. S. J.; Tap, A.; List, B. J. Am. Chem. Soc. 2016, 138,
10822.(18) Costa, P. R. R.; Cabral, L. M.; Alencar, K. G.; Schmidt, L. L.;
Vasconcellos, M. L. A. A. Tetrahedron Lett. 1997, 38, 7021.(19) For a review on tryptophol and its derivatives, see: Palmieri, A.;
Petrini, M. Nat. Prod. Rep. 2019, 36, 490.(20) Fernandes, R. A.; Brückner, R. Synlett 2005, 1281.(21) Eey, S. T.-C.; Lear, M. J. Chem. Eur. J. 2014, 20, 11556.
(22) Wang, P.; Zhao, J.-Z.; Li, H.-F.; Liang, X.-M.; Zhang, Y.-L.; Da, C.-S.Tetrahedron Lett. 2017, 58, 129.
(23) Doyle, A. G. Ph.D. Thesis; Harvard University: Cambridge, 2008.(24) Selected reviews on hydrogen bonding catalysis: (a) Schreiner,
P. R. Chem. Soc. Rev. 2003, 32, 289. (b) Takemoto, Y. Org. Biomol.Chem. 2005, 3, 4299. (c) Taylor, M. S.; Jacobsen, E. N. Angew.Chem. Int. Ed. 2006, 45, 1520. (d) Connon, S. J. Chem. Eur. J. 2006,12, 5418. (e) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107,5713. (f) Yu, X.; Wang, W. Chem. Asian J. 2008, 3, 516.(g) Hydrogen Bonding in Organic Synthesis; Pihko, P. M., Ed.;Wiley-VCH: Weinheim, 2009. (h) Schenker, S.; Zamfir, A.;Freund, M.; Tsogoeva, S. B. Eur. J. Org. Chem. 2011, 2209.(i) Auvil, T. J.; Schafer, A. G.; Mattson, A. E. Eur. J. Org. Chem.2014, 2633. (j) Žabka, M.; Šebesta, R. Molecules 2015, 20, 15500.(k) Nishikawa, Y. Tetrahedron Lett. 2018, 59, 216. (l) Reep, C.;Sun, S.; Takenaka, N. Asian J. Org. Chem. 2019, 8, 1306.
(25) Selected reviews on asymmetric anion-binding catalysis:(a) Zhang, Z.; Schreiner, P. R. Chem. Soc. Rev. 2009, 38, 1187.(b) Mahlau, M.; List, B. Angew. Chem. Int. Ed. 2013, 52, 518.(c) Brak, K.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2013, 52, 534.(d) Seidel, D. Synlett 2014, 25, 783. (e) Busschaert, N.;Caltagirone, C.; Van Rossom, W.; Gale, P. A. Chem. Rev. 2015,115, 8038. (f) Attard, J. W.; Osawa, K.; Guan, Y.; Hatt, J.; Kondo,S.-i.; Mattson, A. Synthesis 2019, 51, 2107.
(26) Lombardo, V. M.; Thomas, C. D.; Scheidt, K. A. Angew. Chem. Int.Ed. 2013, 52, 12910.
(27) Selected reviews on asymmetric Brønsted acid catalysis:(a) Yamamoto, H.; Futatsugi, K. Angew. Chem. Int. Ed. 2005, 44,1924. (b) Akiyama, T. Chem. Rev. 2007, 107, 5744. (c) Terada, M.Synthesis 2010, 1929. (d) Rueping, M.; Nachtsheim, B. J.;Ieawsuwan, W.; Atodiresei, I. Angew. Chem. Int. Ed. 2011, 50,6706. (e) Yu, J.; Shi, F.; Gong, L. Z. Acc. Chem. Res. 2011, 44, 1156.(f) Parmar, D.; Sugiono, E.; Raja, S.; Rueping, M. Chem. Rev. 2014,114, 9047. (g) Akiyama, T.; Mori, K. Chem. Rev. 2015, 115, 9277.(h) Rueping, M.; Parmar, D.; Sugiono, E. Asymmetric BrønstedAcid Catalysis; Wiley-VCH: Weinheim, 2015. (i) Mitra, R.;Niemeyer, J. ChemCatChem 2018, 10, 1221. (j) Sedgwick, D. M.;Grayson, M. N.; Fustero, S.; Barrio, P. Synthesis 2018, 50, 1935.
(28) Ascic, E.; Ohm, R. G.; Petersen, R.; Hansen, M. R.; Hansen, C. L.;Madsen, D.; Tanner, D.; Nielsen, T. E. Chem. Eur. J. 2014, 20,3297.
(29) Zhao, C.; Chen, S. B.; Seidel, D. J. Am. Chem. Soc. 2016, 138, 9053.(30) For reviews on iminium catalysis, see: (a) Erkkilae, A.;
Majander, I.; Pihko, P. M. Chem. Rev. 2007, 107, 5416. (b) Brazier,J. B.; Tomkinson, N. C. O. In Asymmetric Organocatalysis; List, B.,Ed.; Springer: Berlin, 2010, 281.
(31) Das, S.; Liu, L.; Zheng, Y.; Alachraf, M. W.; Thiel, W.; De C, K.;List, B. J. Am. Chem. Soc. 2016, 138, 9429.
(32) Maskeri, M. A.; O’Connor, M. J.; Jaworski, A. A.; Davies, A. V.;Scheidt, K. A. Angew. Chem. Int. Ed. 2018, 57, 17225.
(33) Reisman, S. E.; Doyle, A. G.; Jacobsen, E. N. J. Am. Chem. Soc.2008, 130, 7198.
(34) For the first report describing catalytic enantioselective addi-tions to oxocarbenium ions, see: Braun, M.; Kotter, W. Angew.Chem. Int. Ed. 2004, 43, 514.
(35) (a) Maity, P.; Srinivas, H. D.; Watson, M. P. J. Am. Chem. Soc.2011, 133, 17142. (b) Watson, M. P.; Maity, P. Synlett 2012, 23,1705.
(36) Dasgupta, S.; Rivas, T.; Watson, M. P. Angew. Chem. Int. Ed. 2015,54, 14154.
(37) Meng, Z.; Sun, S.; Yuan, H.; Lou, H.; Liu, L. Angew. Chem. Int. Ed.2014, 53, 543.
SynOpen 2019, 3, 77–90
90
Z. Zhu et al. Short ReviewSyn Open
(38) While not catalytic, enantioselective modification of parent iso-chroman had previously been achieved by deprotonation witht-BuLi in the presence of superstoichiometric amounts of achiral ligand, followed by treatment with various electrophiles,see: Tomooka, K.; Wang, L.-F.; Okazaki, F.; Nakai, T. TetrahedronLett. 2000, 41, 6121.
(39) Catalytic enantioselective additions of boronic acids to struc-turally related chrome acetals are significantly more developed.See, for example: Moquist, P. N.; Kodama, T.; Schaus, S. E.Angew. Chem. Int. Ed. 2010, 49, 7096.
(40) Wan, M.; Sun, S.; Li, Y.; Liu, L. Angew. Chem. Int. Ed. 2017, 56,5116.
(41) Li, Y.; Wan, M.; Sun, S.; Fu, Z.; Huang, H.; Liu, L. Org. Chem. Front.2018, 5, 1280.
(42) Lu, R.; Li, Y.; Zhao, J.; Li, J.; Wang, S.; Liu, L. Chem. Commun.2018, 54, 4445.
(43) (a) Miyata, K.; Kutsuna, H.; Kawakami, S.; Kitamura, M. Angew.Chem. Int. Ed. 2011, 50, 4649. (b) Miyata, K.; Kitamura, M.Synthesis 2012, 44, 2138.
(44) Ammann, S. E.; Liu, W.; White, M. C. Angew. Chem. Int. Ed. 2016,55, 9571.
(45) Liu, S.; Nakajima, K.; Nishibayashi, Y. RSC Adv. 2019, 9, 18918.(46) Ravindra, B.; Maity, S.; Das, B. G.; Ghorai, P. J. Org. Chem. 2015,
80, 7008.(47) Chung, Y. K.; Fu, G. C. Angew. Chem. Int. Ed. 2009, 48, 2225.(48) Zhang, J.-W.; Cai, Q.; Shi, X.-X.; Zhang, W.; You, S.-L. Synlett
2011, 1239.(49) Cai, Q.; Zhao, Z.-A.; You, S.-L. Angew. Chem. Int. Ed. 2009, 48,
7428.(50) Chen, J.; Han, X.; Lu, X. Angew. Chem. Int. Ed. 2017, 56, 14698.
SynOpen 2019, 3, 77–90
