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

2. Introduction
Mechanistic Aspects
Selected Reactions Involving Hydroamination

3. 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

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

5. 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.

6. 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.

7. 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.

8. 2.3 Group 4/5 Metal Based Catalysts
α-elimination
Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 2923–2924.

9. 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.

10. 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.

11. 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

12. 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.

13. 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.

14. 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

15. 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.

16. 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

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

18. 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: /j.molcata

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

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

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

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

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

29. 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

31. 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

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

33. 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, – 13573;

34. 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

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

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

37. 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

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

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

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

41. 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

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

43. 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

44. Thanks