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Catalytic Hydroamination of Alkynes and Alkenes

Zhi-Yong,Han

14.Nov.,2009

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1. Introduction

2.Mechanistic Aspects

3.Selected Reactions Involving Hydroamination

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a high reaction barrier

slightly exothermic

but

entropically negative

Amines: nucleophilic

Alkenes and Alkynes: electron richstrong electron repulsion

Problems:

1. Introduction

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Number of articles published on hydroaminationUntil 2008.3 ,61 review articles covering many aspectsof hydroamination have been published

alkali and lanthanide zirconium, titanium, and late transition metal

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2.1 Rare-Earth Metals Catalysts

Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673–686.

Merits: highly efficient for intramolecular hydroamination with very high turnover frequencies and excellent stereoselectivities Demerits: air and moisture sensitive,and cannot tolerate acidic substrates

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Molander, G. A.; Hasegawa, H. Heterocycles 2004, 64, 467–474.

Li, Y.; Fu, P.-F.; Marks, T. J. Organometallics 1994, 13, 439–440. Li, Y.; Marks, T. J. J. Am. Chem. Soc. 1996, 118, 9295–9306.

radius of the rare-earth metal ion↓

Catalytic activity ↑

Gagne´, M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem.Soc. 1992, 114, 275–294.

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2.2 Alkaline Earth Metals Catalysts

The chemistry of organometallic alkaline earth metal complexes is closely related to that of the rare-earth elements

Buch, F.; Harder, S. Z. Naturforsch. 2008, 63b, 169–177.

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2.3 Group 4/5 Metal Based Catalysts

Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 2923–2924.

α-elimination

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Ackermann, L. Organometallics 2003, 22, 4367–4368.

Odom, A. L. Org. Lett.2004, 6, 2957–2960.

Beller, M. Angew. Chem., Int. Ed. 2002, 41, 2541–2543.Beller, M. Chem. Eur. J. 2004, 10, 2409–2420.

Doye, S. Org. Lett. 2000, 2, 1935–1937.

Substrate affected anti-Markovnikov

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highly anti-Markovnikov

Schafer, L. L. Org. Lett. 2003, 5, 4733–4736. Schafer, L. L.Chem. Eur. J. 2007, 13, 2012–2022.

Wren, S. L. Organometallics 2003, 22, 4393–4395.

One pot reaction

Doye, S. Angew. Chem., Int.Ed. 2005, 44, 2951–2954.

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2.4 Late Transition Metal Catalysts

Ru(0), Rh(I)/Rh(III), Ir(I)/Ir(III), Pd(II), Pt(II), Pt(IV), Cu(I), Zn(II), Au(I)/Au(III),Ag(I), Ni(0), Re(I), Fe(III), Bi(III), and toxic Cd(II), Hg(II)

Four different categories of mechanism

1. nucleophilic attack on a coordinated alkene or alkyne

2. nucleophilic attack on allylic complexes

3. insertion of the alkene/alkyne into a metal-hydride bond

4. oxidative addition of the amine, followed by insertion into the metal-amide bond

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2.4.1 Nucleophilic Attack on Coordinated Alkene/Alkyne

Muller, T. E., Organometallics 2000, 19,170–183.

the rate-determining step of such a catalytic cycle would be the cleavage of the metal-carbon bond

DFT calculations indicate that group 10 catalysts preferentially react via path A, while group 9 catalysts are inclined to path B

13Crabtree, R. H. Org. Lett. 2005, 7, 5437–5440.

Catalyst resting state○ represents [23]● represents [27]

The choice of the amine is a critical feature of hydroamination with late transition metal complexes.

rate=k1*[34]=k1*k2*[33]=k1*k2*k3*[23][32]= k1*k2*k3*[23]*k4/[23]=k1k2k3k4

Reaction rates are generally higher, the lower the basicity of the amine nucleophile is.

Thomas E. Muller,Chem. Rev. 2008, 108, 3795–3892

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Ar

NH2

+ [Pt(cod)](TfO)2 NHAr

For alkenes: the less basic the amine is, the faster the reaction proceeds

For alkynes: more acidic amine or amide N-H, means less nucleophilic and slower reaction rate

Tilley, T. D. J. Am. Chem. Soc. 2005,127, 12640–12646.Takemoto, Y.,SYNLETT, 2008, 11, 1647–1650

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rhodium-catalyzed, anti-Markovnikov oxidative amination

Beller, M. Angew. Chem., Int. Ed.Engl. 1997, 36, 2225–2227.

a tridentate ligand would block the open coordination sites required for â-hydride elimination,

Michael, F. E., J. Am. Chem. Soc. 2006, 128, 4246–4247.

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2.4.2 Nucleophilic Attack on Allylic Complexes

Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421–5424

Yamamoto, Y. J. Am. Chem. Soc. 2004,126, 1622–1623.Yamamoto, Y. J. Org. Chem.1999, 64, 4570–4571.

17Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 2702–2703

Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5756–5757.

Michael type

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2.4.3 Insertion into the M-H Bond of Metal Hydrides

Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546–9547Muller, T. E. J. Mol. Catal. A. Catal. 2007, available online, doi: 10.1016/j.molcata.2007.06.016.

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2.4.4 Oxidative Addition

Activation of the amine by oxidative addition to acoordinatively unsaturated late transition metal in low oxidation state

Ru0/RuII,RhI/RhIII, IrI/IrIII, Pt0/PtII, CuI/CuIII

Effective couples:

Hartwig, J. F. Science 2005, 307, 1080–1082.

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Muller, T. E. Tetrahedron 2001, 57, 6027–6033.

H2Ntoluene,110oC3.5h, >99%

Cu(C6H6)Cu(OTf)2(1%)

N

H2Ntoluene,110oC0.5h, >99%

Pd(triphos)(OTf)2/10TfOH

N

10%

Muller, T. E.;J. Catal. 2004, 221, 302.

NH2

THF,67oC N

Rh(bim)(CO)2BPh4 75%

Cat.(1.5%) Rh(bpm)(CO)2BPh4 98%

Ir(bim)(CO)2BPh4 98%

Ir(bpm)(CO)2BPh4 98%

Turner, P. Organometallics 2004, 23, 1714–1721.

Ru3(CO)12 110oC 78%

Reusable Cat.

3. Selected Reactions Involving Hydroamination

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NH2

THF,67oC N

Cat.(1.5%)

Ph

Ph

Ru3(CO)12 150oC >99%

RuBr(C3H5)(CO)3 150oC >99%

Ru(cot)(dmfm)2 150oC 83%

[RuCl2(CO)3]2 150oC 93%

Mitsudo, T.-A. J. Organomet.Chem. 2001, 622, 149–154

O

Cl3CNH

Cat. O

NCl3C

AuCl3 20oC 69%

AuP(C6F5)3SbF6 0oC 98%

Hashmi, A. S. K.; Eur. J. Org. Chem. 2006, 4905–4909.

Reaction rate: Ph > H > Me>>SiR3

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Intermolecular hydroamination of aniline and aryl or alkynes

Liu,X-Y.Che,Z.-M. Org. Lett. 2009, 11, 4204–4207.

Hartung, C. G.; Tillack, A.; Trauthwein, H.; Beller, M. J. Org. Chem.2001, 66, 6339–6343.

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Mitsudo, T.-A. J. Organomet.Chem. 2001, 622, 149–154.

NH2

Cat.

NH

cat. temp. yield

Ru3(CO)12 110 54

Rh(N-N)(CO)2BPh455 55

Messerle, B. A. Organometallics 2000, 19, 87–90cat. temp. yield

Pd(Triphos)(OTf)2 40 100Zn(OTf)2 110 34Cu(MeCN)4PF6 82 100NH2

Cat.

NH

Ph Ph

Liu, S. T. Organometallics 2007, 26, 1062–1068.

Muller, T. E.;. Organometallics 2000, 19, 170–183.

Burling, S.; Aust.J. Chem. 2004, 57, 677–680.

cat. temp. yield

Rh(N-N)(CO)2]BPh4 55 23NHAc

Cat.

NAc

NHAc

Cat.

NAc

nBu nBu

Ir(H)(Cl)(C-N-P)CO 110 21

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Double Hydroamination

Zhang, Y.; Donahue, J. P.; Li, C. J. Org. Lett. 2007, 9, 627–630.

Sun, L.-P.; Huang, X.-H.; Dai, W.-M. Tetrahedron 2004, 60, 10983–10992.

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ArNH2 + Ar'CONH2 +

R PhI(OAc)2 Au(cat.)

O

NHAr'ArHN

R

Au

O

NAr'ArN

R

ArNH2 + Ar'CONH2 +

R PhI(OAc)2 Chiral Au(cat.)

O

NHAr'ArHN

R

Chiral Au(cat.)

O

NAr'ArN

R

Reiko Yanada* Angew. Chem., Int. Ed.Engl. 2009, ASAP.

Isocyanate mediated tandem reaction

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Application of Ynamides

Skrydstrup,T.,Org. Lett., 11, 2009, 221

Ynamides are more reactive than alkynes

Skrydstrup,T.,Org. Lett., 11, 2009, 4208

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N-H insertion tandem hydroamination

Jian-Bo, Wang, Adv. Synth. Catal. 2008, 350, 2359 – 2364

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Hydroamination/Heck reaction sequence

Lutz Ackermann, Chem. Commun. , 2004, 2824

Ning Jiao, Angew. Chem. Int. Ed. 2009, 48, 4572 –4576

Hydroamination/Oxidation tandem reaction

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Intramolecular amide N-H and yne hydromation via M+Base or TBAF

Why double Fluoro substrate were selected? (Vide infra)

Hammond,G.,B., Org. Lett., 9, 2007, 4251

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Re catalyzed cyclic amide N-H yne hydroamination

R=t-Bu, Bn, AlkaneNo Aryl yne substrates

anti-Markovnikov products only

Takai,K., Org. Lett., 9, 2007, 5609

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A Rh catlyzed tandem reaction

This product may be reducted by Hantzsh ester catlyzed by bronsted acid

Fukumoto,Y., Org. Lett., 8, 2006, 4641

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Hydroamination using ammonia

These gold above catalysts are very robust !

Ph3PAuMe+PhPA <<< Ph3PAuCl/AgOTf << tBuAuCl/AgOTf

Bertrand,G.,Angew. Chem. Int. Ed. 2008, 47, 5224 –5228

G. Bertrand, Proc. Natl. Acad. Sci. USA 2007, 104, 13569 – 13573;

Bertrand,G., J. AM. CHEM. SOC. 2009, 131, 8690–8696

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Hydroxyl group assisted hydroamination/hydroarylation tandem

This protocol became less useful after effective catalysts were found,

Maybe less active amide/yne sbustrates could be used

Or design new reactions than could make the hydroxyl group useful.

Nitin T. Patil, J. Org. Chem. 2009, 74, 6315–6318

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Liu, Xin-Yuan, Che, Chi-Ming, Angew. Chem. Int. Ed. 2009, 48, 2367 –2371

Liu, Xin-Yuan, Che, Chi-Ming, Chem. Int. Ed. 2008, 47, 3805 – 3810.

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Ru catalyzed amide/alkyne hydroamination reaction

100oC 15h

Lukas J. Goobn, Angew. Chem. Int. Ed. 2005, 44, 4042 –4045

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Ru catalyzed amide/alkyne hydroamination

Method A: 1.00 mmol benzamide, 2.00 mmol 1-hexyne, 5 mol% [(cod)Ru(met)2], 6 mol% dcypb, 4 mol% Yb(OTf)3, 3 mL DMF and 108 mL wateras co-solvent, 60 oC, 6 h. Method B: After complete conversionfollowing method A, 3 molecular sieves (500 mg) and triethylamine (200 mL) were added, and the mixture was heated to 1108C for 24 h.

Lukas J. Goossn, Angew. Chem. Int. Ed. 2008, 47, 8492 –8495

Catalyst formation

Question: is the catalyst acid-torleratable?

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Rh catalyzed Amide/Alkyne hydroamination/oxidation-coupling tandem

No external alkynes substrates

Keith Fagnou, JACS, 130, 2008, 16474

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Phthalimide/Activated alkyne hydroamination oxidation tandem

Nai-Xing Wang, and Jin-Heng Li ,10, 2008, 1179

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Secondary amine, alkyne and activated alkyne multicomponent reacton

Chao-Jun,Li, Adv. Synth. Catal. 2008, 350, 2226 – 2230

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Copper catalyzed Alkyne, azide and amine or H2O multicomponent reaction

amidine

Sukbok Chang J. AM. CHEM. SOC. ,127, 2005, 16047Sukbok Chang J. AM. CHEM. SOC. 127 ,2005, 2038

Question: Can the C=N bond in amidine be used in organocatalyzed reaction?

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Insitu formation of activated alkyne then hydroamination

Hirokazu Urabe, J. AM. CHEM. SOC. 2008, 130, 1820-1821

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amide and oxygen activated alkyne hydroamination reaction

The C-C double bond in the product should be active for many tandem reactions

Sergey A. Kozmin, Angew. Chem. Int. Ed. 2006, 45, 4991 –4993

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Thanks