Catalytic Hydroamination of Alkynes and Alkenes Zhi-Yong,Han 14.Nov.,2009

Introduction Mechanistic Aspects Selected Reactions Involving Hydroamination

Problems: slightly exothermic but a high reaction barrier 1. Introduction Problems: slightly exothermic but a high reaction barrier entropically negative Amines: nucleophilic Alkenes and Alkynes: electron rich strong electron repulsion

Number of articles published on hydroamination Until 2008.3 ,61 review articles covering many aspects of hydroamination have been published alkali and lanthanide zirconium, titanium, and late transition metal

2.1 Rare-Earth Metals Catalysts Merits: highly efficient for intramolecular hydroamination with very high turnover frequencies and excellent stereoselectivities Demerits: air and moisture sensitive, and cannot tolerate acidic substrates Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673–686.

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.

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.

2.3 Group 4/5 Metal Based Catalysts α-elimination Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 2923–2924.

Substrate affected anti-Markovnikov Ackermann, L. Organometallics 2003, 22, 4367–4368. 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. Odom, A. L. Org. Lett.2004, 6, 2957–2960.

One pot reaction Wren, S. L. Organometallics 2003, 22, 4393–4395. highly anti-Markovnikov Schafer, L. L. Org. Lett. 2003, 5, 4733–4736. Schafer, L. L.Chem. Eur. J. 2007, 13, 2012–2022. Doye, S. Angew. Chem., Int.Ed. 2005, 44, 2951–2954.

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 nucleophilic attack on a coordinated alkene or alkyne nucleophilic attack on allylic complexes insertion of the alkene/alkyne into a metal-hydride bond oxidative addition of the amine, followed by insertion into the metal-amide bond

2.4.1 Nucleophilic Attack on Coordinated Alkene/Alkyne DFT calculations indicate that group 10 catalysts preferentially react via path A, while group 9 catalysts are inclined to path B the rate-determining step of such a catalytic cycle would be the cleavage of the metal-carbon bond Muller, T. E., Organometallics 2000, 19,170–183.

rate=k1*[34]=k1*k2*[33]=k1*k2*k3*[23][32] 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 Crabtree, R. H. Org. Lett. 2005, 7, 5437–5440.

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

rhodium-catalyzed, anti-Markovnikov oxidative amination a tridentate ligand would block the open coordination sites required for â-hydride elimination, Beller, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 2225–2227. Michael, F. E., J. Am. Chem. Soc. 2006, 128, 4246–4247.

2.4.2 Nucleophilic Attack on Allylic Complexes Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 1622–1623. Yamamoto, Y. J. Org. Chem.1999, 64, 4570–4571. Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421–5424

Michael type Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 5756–5757. Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 2702–2703

2.4.3 Insertion into the M-H Bond of Metal Hydrides Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546–9547 Muller, T. E. J. Mol. Catal. A. Catal. 2007, available online, doi: 10.1016/j.molcata.2007.06.016.

2.4.4 Oxidative Addition Effective couples: Ru0/RuII,RhI/RhIII, IrI/IrIII, Pt0/PtII, CuI/CuIII Activation of the amine by oxidative addition to acoordinatively unsaturated late transition metal in low oxidation state Hartwig, J. F. Science 2005, 307, 1080–1082.

3. Selected Reactions Involving Hydroamination Muller, T. E. Tetrahedron 2001, 57, 6027–6033. Muller, T. E.;J. Catal. 2004, 221, 302. Reusable Cat. Turner, P. Organometallics 2004, 23, 1714–1721.

Mitsudo, T.-A. J. Organomet.Chem. 2001, 622, 149–154 Reaction rate: Ph > H > Me>>SiR3 Hashmi, A. S. K.; Eur. J. Org. Chem. 2006, 4905–4909.

Intermolecular hydroamination of aniline and aryl or alkynes Hartung, C. G.; Tillack, A.; Trauthwein, H.; Beller, M. J. Org. Chem.2001, 66, 6339–6343. Liu,X-Y.Che,Z.-M. Org. Lett. 2009, 11, 4204–4207.

Mitsudo, T.-A. J. Organomet.Chem. 2001, 622, 149–154. Messerle, B. A. Organometallics 2000, 19, 87–90 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.

Double Hydroamination Sun, L.-P.; Huang, X.-H.; Dai, W.-M. Tetrahedron 2004, 60, 10983– 10992. Zhang, Y.; Donahue, J. P.; Li, C. J. Org. Lett. 2007, 9, 627–630.

Isocyanate mediated tandem reaction Reiko Yanada* Angew. Chem., Int. Ed.Engl. 2009, ASAP.

Application of Ynamides Skrydstrup,T.,Org. Lett., 11, 2009, 221 Ynamides are more reactive than alkynes Skrydstrup,T.,Org. Lett., 11, 2009, 4208

N-H insertion tandem hydroamination Jian-Bo, Wang, Adv. Synth. Catal. 2008, 350, 2359 – 2364

Hydroamination/Heck reaction sequence Lutz Ackermann, Chem. Commun. , 2004, 2824 Hydroamination/Oxidation tandem reaction Ning Jiao, Angew. Chem. Int. Ed. 2009, 48, 4572 –4576

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

Re catalyzed cyclic amide N-H yne hydroamination R=t-Bu, Bn, Alkane No Aryl yne substrates anti-Markovnikov products only Takai,K., Org. Lett., 9, 2007, 5609

A Rh catlyzed tandem reaction This product may be reducted by Hantzsh ester catlyzed by bronsted acid Fukumoto,Y., Org. Lett., 8, 2006, 4641

Hydroamination using ammonia Bertrand,G.,Angew. Chem. Int. Ed. 2008, 47, 5224 –5228 Bertrand,G., J. AM. CHEM. SOC. 2009, 131, 8690–8696 These gold above catalysts are very robust ! G. Bertrand, Proc. Natl. Acad. Sci. USA 2007, 104, 13569 – 13573;

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

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

Ru catalyzed amide/alkyne hydroamination reaction 100oC 15h Lukas J. Goobn, Angew. Chem. Int. Ed. 2005, 44, 4042 –4045

Ru catalyzed amide/alkyne hydroamination Question: is the catalyst acid-torleratable? Catalyst formation 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 conversion following 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

Rh catalyzed Amide/Alkyne hydroamination/oxidation-coupling tandem No external alkynes substrates Keith Fagnou, JACS, 130, 2008, 16474

Phthalimide/Activated alkyne hydroamination oxidation tandem Nai-Xing Wang, and Jin-Heng Li ,10, 2008, 1179

Secondary amine, alkyne and activated alkyne multicomponent reacton Chao-Jun,Li, Adv. Synth. Catal. 2008, 350, 2226 – 2230

Copper catalyzed Alkyne, azide and amine or H2O multicomponent reaction amidine Question: Can the C=N bond in amidine be used in organocatalyzed reaction? Sukbok Chang J. AM. CHEM. SOC. ,127, 2005, 16047 Sukbok Chang J. AM. CHEM. SOC. 127 ,2005, 2038

Insitu formation of activated alkyne then hydroamination Hirokazu Urabe, J. AM. CHEM. SOC. 2008, 130, 1820-1821

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

Thanks