Presentation on theme: "Paladium Catalysed Transformations in Organic Synthesis"— Presentation transcript:
1 Paladium Catalysed Transformations in Organic Synthesis Palladium-Catalyzed Cross-Coupling Reactions in Total Synthesis K. C. Nicolaou, Paul G. Bulger, David Sarlah Angewandte Chemie International Edition Volume 44, Issue 29, PagesPaul Docherty, 2005
2 IntroductionSince Mizoroki developed the first palladium catalysed reaction, research in this area has developed exponentially, with each new issue of Angewandte Chemie or JACS highlighting the latest techniques and processes.These reactions show a breadth of applications, not just in the type of transformation, but in the target structure and scale of the process. Indeed, it is common to see the retrosynthesis of industrial targets hinge upon a crucial palladium-mediated reaction.PdT. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581(There is still some debate as to which coupling was developed first; many claim that the Kumada coupling of sp2 grignard reagents with aryl, vinyl or alkyl halides was the first. However, the intrinsic reactivity of grignard reagents with other common functionalities mean that this coupling is seldom used.)
3 Why Palladium?Why is palladium such an adept catalyst centre? Why not sodium?The reason seems to be based around its electronegativity, which leads to relatively strong Pd-H and Pd-C bonds, and also develops a polarised Pd-X bond.It allows easy access to the Pd (II) and Pd (0) oxidation states, essential for processes such as oxidative addition, transmetalation and reductive elimination,Pd (I), Pd (III) and Pd (IV) complexes are also known, though less thoroughly, with Pd (IV) species essential in C-H activation mechanisms.2. Pd (VI) complexes has also been proposed (W. Chen, S. Shimada, M. Tanaka, Science, 2002, 295, 308), but theoretical articles counter-argue this (E. C. Sherer, C. R. Kinsinger, B. L. Kormos, J.D. Thompson, C. J. Cramer Angew. Chem., Int. Ed. 2002, 41, 1953). The debate is ongoing.
4 The Heck ReactionBroadly defined as the palladium-catalyzed coupling of alkenyl or aryl (sp2) halides or triflates with alkenes to yield products which formally result from the substitution of a hydrogen atom in the alkene coupling partner.First discovered by Mizoroki, though developed and applied more thoroughly by Richard F. Heck in the early 1970s.Generally thought of as the original palladium catalysed cross-coupling, and probably the best evolved, including a multitude of asymmetric varients.R. F. Heck, J. P. Nolley, Jr., J. Org. Chem. 1972, 37, 2320Review on asymmetric Heck reactions: A. B. Dounay, L. E. Overman, Chem. Rev. 2003, 103, 2945 – 2963
6 Mechanism of the Heck Reaction cationic Abelman, M. M.; Oh, T.; Overman, L. E. J. Org. Chem. 1987, 52, 4133–4135.
7 Regioselectivity in the Heck Reaction The type of mechanism in action is incredibly important, as it can manifest itself in a variety of ways, especially the regioselectivity.In the neutral catalytic cycle, the regioselectivity is governed by steric factors – generally addition occurs to the terminal end of the alkene.However, in the cationic cycle, regiochemistry is affected by electronics. The cationic Pd complex increases the polarization of the alkene favouring transfer of the vinyl or aryl group to the site of least electron density.The type of mechanism in effect is generally controlled by choice of halide/pseudohalide acting as a leaving group in the cationic cycle; triflate promotes, whereas bromide detracts.a) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2–7.b) Cabri, W.; Candiani, I.; Bedeschi, A.; Penco, S.; Santi, R. J. Org. Chem. 1992, 57, 1481–1486.
8 The Heck Reaction: Dehydrotubifoline a) V. H. Rawal, C. Michoud, R. F. Monestel, J. Am. Chem. Soc. 1993, 115, 3030 – 3031b) V. H. Rawal, C. Michoud, J. Org. Chem. 1993, 58, 5583 – 5584.
9 The Heck Reaction: Capnellene a) K. Kagechika, M. Shibasaki, J. Org. Chem. 1991, 56, 4093 –4094b) K. Kagechika, T. Ohshima, M. Shibasaki, Tetrahedron, 1993, 49, 1773 – 1782.
10 The Heck Reaction: Taxol a) S. J. Danishefsky, J. J. Masters, W. B. Young, J. T. Link, L. B. Snyder, T. V. Magee, D. K. Jung, R. C. A. Isaacs, W. G. Bornmann, C. A. Alaimo, C. A. Coburn, M. J. Di Grandi, J. Am. Chem. Soc. 1996, 118, 2843 – 2859b) J. J. Masters, J. T. Link, L. B. Snyder, W. B. Young, S. J. Danishefsky, Angew. Chem. Int. Ed. Engl. 1995, 34, 1723 – 1726.
11 The Heck Reaction: Estrone L. F. Tietze, T. NVbel, M. Spescha, J. Am. Chem. Soc. 1998, 120, 8971 – 8977.
12 Domino Heck ReactionsY. Zhang, G.Wu, G. Angel, E. Negishi, J. Am. Chem. Soc. 1990, 112, 8590 – 8592.
13 Domino Heck Reactionsa) L. E. Overman, D. J. Ricca, V. D. Tran, J. Am. Chem. Soc. 1993, 115, 2042 – 2044b) D. J. Kucera, S. J. OIConnor, L. E. Overman, J. Org. Chem. 1993, 58, 5304 – 5306.
14 The Stille CouplingOriginally discovered by Kosugi et al in the late 1970s, the Stille Coupling was later developed as a tool for organic transformations by the late Professor J. K. Stille.Milder than the older Heck reaction, and more functional-group tolerant, the Stille coupling remains popular in organic synthesis.A close relative of the Stille coupling is the Hiyama; this involves the palladium catalysed reaction of a organosilicon with organic halides/triflates et c., but requires activation with fluoride (TBAF) or hydroxide.It is possible to couple bis-aryl halides using R3Sn-SnR3, in a varient known as a Stille-Kelly reaction, but the toxicity of these species is a somewhat limiting factor.Original Report; a) M. Kosugi, K. Sasazawa, Y. Shimizu, T. Migita, Chem. Lett. 1977, 301 – 302; b) M. Kosugi, K. Sasazawa, T. Migita, Chem. Lett. 1977, 1423 – 1424.a) D. Milstein, J. K. Stille, J. Am. Chem. Soc. 1978, 100, 3636 – 3638; b) D. Milstein, J. K. Stille, J. Am. Chem. Soc. 1979, 101, 4992 – 4998; c) For a review of Stille Reactions, see; V. Farina, V. Krishnamurthy,W. J. Scott, Org. React. 1997, 50, 1 – 652T. Hiyama, Y. Hatanaka, Pure Appl. Chem. 1994, 66, 1471T. R. Kelly, Tetrahedron Lett. 1990, 31, 161
16 The Stille Coupling: Rapamycin a) K. C. Nicolaou, T. K. Chakraborty, A. D. Piscopio, N. Minowa, P. Bertinato, J. Am. Chem. Soc. 1993, 115, 4419 – 4420; K. C. Nicolaou, A. D. Piscopio, P. Bertinato, T. K. Chakraborty, , N. Minowa, K. Koide, Chem. Eur. J. 1995, 1, 318 –333.b) A. B. Smith III, S. M. Condon, J. A. McCauley, J. L. Leazer, Jr.,J. W. Leahy, R. E. Maleczka, Jr., J. Am. Chem. Soc. 1995, 117, 5407 – 5408.
17 The Stille Coupling: Dynamycin a) M. D. Shair, T.-Y. Yoon, K. K. Mosny, T. C. Chou, S. J. Danishefsky, J. Am. Chem. Soc. 1996, 118, 9509 – 9525;b) M. D. Shair, T.-Y. Yoon, S. J. Danishefsky, Angew. Chem. 1995, 107, 1883 – 1885; Angew. Chem. Int. Ed. Engl. 1995, 34, 1721 – 1723;c) M. D. Shair, T. Yoon, S. J. Danishefsky, J. Org. Chem. 1994, 59, 3755 – 3757.
18 The Stille Coupling: Sanglifehrin a) K. C. Nicolaou, J. Xu, F. Murphy, S. Barluenga, O. Baudoin, H.-X.Wei, D. L. F. Gray, T. Ohshima, Angew. Chem. Int. Ed. 1999, 38, 2447 – 2451;b) K. C. Nicolaou, F. Murphy, S. Barluenga, T. Ohshima, H. Wei, J. Xu, D. L. F. Gray, O. Baudoin, J. Am. Chem. Soc. 2000, 122, 3830 – 3838.
19 The Stille Coupling: Manzamine A a) S. F. Martin, J. M. Humphrey, A. Ali, M. C. Hillier, J. Am. Chem. Soc. 1999, 121, 866 – 867;b) J. M. Humphrey, Y. Liao, A. Ali, T. Rein, Y.-L. Wong, H.-J. Chen, A. K. Courtney, S. F. Martin, J. Am. Chem. Soc. 2002, 124, 8584 – 8592.
20 The Carbonylative Stille Coupling: Jatrophone A. C. Gyorkos, J. K. Stille, L. S. Hegedus, J. Am. Chem. Soc. 1990, 112, 8465 – 8472.
21 The Suzuki CouplingThe Suzuki reaction was formally developed by Suzuki Group in 1979, although the inspiration for this work can be traced back to publications by Heck and Negishi, and their earlier presentation of these papers at conferences.The popularity of this reaction can be partially attributed to the ease of preparation of the organoboron reagents required, their general stability, and the lack of toxic by-products.Progress in the last quarter-century has shown that the Suzuki reaction is incredibly powerful, with examples of C(sp2)–C(sp3) and even C(sp3)–C(sp3) now well documented.Original Report; a) N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. 1979, 20, 3437 – 3440; b) N. Miyaura, A. Suzuki, J. Chem. Soc. Chem. Commun. 1979, 866 – 867a) R. F. Heck in Proceedings of the Robert A. Welch Foundation Conferences on Chemical Research XVII. Organic-Inorganic Reagents in Synthetic Chemistry (Ed.W. O. Milligan), 1974, p. 53–98; b) H. A. Dieck, R. F. Heck, J. Org. Chem. 1975, 40, 1083 – 1090.E. Negishi in Aspects of Mechanism and Organometallic Chemistry (Ed.: J. H. Brewster), Plenum, New York, 1978, p. 285.a) T. Ishiyama, S. Abe, N. Miyaura, A. Suzuki, Chem. Lett. 1992, 691 – 694. b) J. Zhou, G.C. Fu, J. Am. Chem. Soc. 2004, 126, 1340 – 1341, and references therein. c) A. C. Frisch, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 674 – 688. d) For a relatively recent review, see N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457.
23 The Suzuki Coupling: Palytoxin a) R.W. Armstrong, J.-M. Beau, S. H. Cheon, W. J. Christ, H. Fujioka, W.-H. Ham, L. D. Hawkins, H. Jin, S. H. Kang, Y. Kishi, M. J. Martinelli, W. J. McWhorter, Jr., M. Mizuno, M. Nakata, A. E. Stutz, F. X. Talamas, M. Taniguchi, J. A. Tino, K. Ueda, J.-I. Uenishi, J. B. White, M. Yonaga, J. Am. Chem. Soc. 1989, 111, 7525 – 7530;b) R.W. Armstrong, J.-M. Beau, S. H.Cheon,W. J. Christ, H. Fujioka,W.-H. Ham, L. D. Hawkins, H. Jin, S. H. Kang, Y. Kishi, M. J. Martinelli,W. J. McWhorter, Jr.,M. Mizuno, M. Nakata, A. E. Stutz, F. X. Talamas, M. Taniguchi, J. A. Tino, K. Ueda, J.-I. Uenishi, J. B. White, M.Yonaga, J. Am. Chem. Soc. 1989, 111, 7530 – 7533;c) E. M. Suh, Y. Kishi, J. Am. Chem. Soc. 1994, 116, –
24 The Suzuki Coupling: Palytoxin a) R.W. Armstrong, J.-M. Beau, S. H. Cheon, W. J. Christ, H. Fujioka, W.-H. Ham, L. D. Hawkins, H. Jin, S. H. Kang, Y. Kishi, M. J. Martinelli, W. J. McWhorter, Jr., M. Mizuno, M. Nakata, A. E. Stutz, F. X. Talamas, M. Taniguchi, J. A. Tino, K. Ueda, J.-I. Uenishi, J. B. White, M. Yonaga, J. Am. Chem. Soc. 1989, 111, 7525 – 7530;b) R.W. Armstrong, J.-M. Beau, S. H.Cheon,W. J. Christ, H. Fujioka,W.-H. Ham, L. D. Hawkins, H. Jin, S. H. Kang, Y. Kishi, M. J. Martinelli,W. J. McWhorter, Jr.,M. Mizuno, M. Nakata, A. E. Stutz, F. X. Talamas, M. Taniguchi, J. A. Tino, K. Ueda, J.-I. Uenishi, J. B. White, M.Yonaga, J. Am. Chem. Soc. 1989, 111, 7530 – 7533; c) E. M. Suh, Y. Kishi, J. Am. Chem. Soc. 1994, 116, –
25 The Suzuki Coupling: FR182887 a) D. A. Evans, J. T. Starr, J. Am. Chem. Soc. 2003, 125, –13540b) D. A. Evans, J. T. Starr, Angew. Chem. 2002, 114, 1865 – 1868; Angew. Chem. Int. Ed. 2002, 41, 1787 – 1790.
26 The Suzuki Coupling: Dragmacidin a) N. K. Garg, D. D. Capsi, B. M. Stoltz, J. Am. Chem. Soc. 2004, 126, 9552 – 9553.b) For a failed alternative route without Pd Catalysis: N. K. Garg, R. Sarpong, B. M. Stoltz, J. Am. Chem. Soc. 2002, 124, –
27 The Suzuki-Miyaura B-Alkyl Coupling: CP-236,114 An important trend in Suzuki chemistry is the development of a C(sp3)–C(sp2) methodology, which has become known as the Suzuki-Miyaura B-Alkyl varient.[13-15]Often used as an alternative to RCM, leaving a single isolated double bond, rather than the conjugated systems produced by a regular Suzuki coupling.a) N. Miyaura, T. Ishiyama, M. Ishikawa, A. Suzuki, Tetrahedron Lett. 1986, 27, 6369 – 6372; b) not to be confused with the Miyaura boration, in which an aryl halide is converted to an aryl boronate via palladium catalysis and a diboron reagent. However, this is a useful preparation of the organoboron reagents required for the Suzuki reaction. See: T. Ishiyama, M. Murata, N. Miyuara. J. Org. Chem. 1995, 60, 7508.Review of the development, mechanistic background, and applications of the B-alkyl Suzuki-Miyaura cross-coupling reaction, see S. R. Chemler, D. Trauner, S. J. Danishefsky, Angew. Chem. Int. Ed. 2001, 40, 4544 – 4568.Q. Tan, S. J. Danishefsky, Angew. Chem. Int. Ed. 2000, 39, 4509 – 4511.
28 The Suzuki Coupling: Phomactin A a) P. J. Mohr, R. L. Halcomb, J. Am. Chem. Soc. 2003, 125, 1712 – 1713b) N. C. Callan, R. L. Halcomb, Org. Lett. 2000, 2, 2687 – 2690.
29 The Suzuki Coupling: Yuehhukene M. Ishikura, K. Imaizumi, N. Katagiri, Heterocycles, 2000, 53, 553 – 556
30 The Sonogashira Coupling The coupling of terminal alkynes with vinyl or aryl halides via palladium catalysis was first reported independently and simultaneously by the groups of Cassar and Heck in 1975.A few months later, Sonogashira and co-workers demonstrated that, in many cases, this cross-coupling reaction could be accelerated by the addition of cocatalytic CuI salts to the reaction mixture.[18,19]This protocol, which has become known as the Sonogashira reaction, can be viewed as both an alkyne version of the Heck reaction and an application of palladium catalysis to the venerable Stephens–Castro reaction (the coupling of vinyl or aryl halides with stoichiometric amounts of copper(I) acetylides).Interestingly, the utility of the “copperfree” Sonogashira protocol (i.e. the original Cassar–Heck version of this reaction) has subsequently been “rediscovered” independently by a number of other researchers in recent years.L. Cassar, J. Organomet. Chem. 1975, 93, 253 – 259.H. A. Dieck, F. R. Heck, J. Organomet. Chem. 1975, 93, 259 – 263.K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975, 16, 4467 – 4470.For a brief historical overview of the development of the Sonogashira reaction, see: K. Sonogashira, J. Organomet. Chem. 2002, 653, 46 – 49.R. D. Stephens, C. E. Castro, J. Org. Chem. 1963, 28, 3313 – 3315.a) M. Alami, F. Ferri, G. Linstrumelle, Tetrahedron Lett. 1993, 34, 6403 – 6406; b) J.-P. Genet, E. Blart, M. Savignac, Synlett 1992, 715 – 717; c) C. Xu, E. Negishi, Tetrahedron Lett. 1999, 40, 431 – 434;
32 The Sonogashira Coupling: Eicosanoid 212 K. C. Nicolaou, S. E. Webber, J. Am. Chem. Soc. 1984, 106, 5734 – 5736
33 The Sonogashira Coupling: Disorazole C1 P. Wipf, T. H. Graham, J. Am. Chem. Soc. 2004, 126, –15347.
34 The Sonogashira Coupling: Dynemicin a) J. Taunton, J. L. Wood, S. L. Schreiber, J. Am. Chem. Soc. 1993, 115, – 10379b) J. L. Wood, J. A. Porco, Jr., J. Taunton, A. Y. Lee, J. Clardy, S. L. Schreiber, J. Am. Chem. Soc.1992, 114, 5898 – 5900c) H. Chikashita, J. A. Porco, Jr., T. J. Stout, J. Clardy, S. L. Schreiber, J. Org. Chem. 1991, 56, 1692 – 1694d) J. A. Porco, Jr., F. J. Schoenen, T. J. Stout, J. Clardy, S. L. Schreiber, J. Am. Chem. Soc. 1990, 112, 7410 – 7411.
35 The Tsuji-Trost Reaction The palladium catalysed nucleophilic substitution of allylic compounds was discovered independently by Trost and Tsuji, and represents the first example of a metalated species acting as an electrophile.Originally developed as a stoichiometric process, Trost succeeded in transforming the allylation of enolates with p-allyl–palladium complexes into the catalytic process of renown.[23,24]A wide range of allylic substrates undergo this reaction with a correspondingly wide range of carbanions, making this a versatile and important process for the formation of carbon–carbon bonds.Whilst the most commonly employed substrates for palladium-catalyzed allylic alkylation are allylic acetates, a variety of leaving groups also function effectively—these include halides, sulfonates, carbonates, carbamates, epoxides, and phosphates.For early reviews of the Tsuji-Trost reaction, see a) B. M. Trost, Acc. Chem. Res. 1980, 13, 385 – 393; b) J. Tsuji, Tetrahedron 1986, 42, 4361 – 4401.J. Tsuji, H. Takahashi, Tetrahedron Lett. 1965, 6, 4387 – 4388.For recent reviews of the palladium-catalyzed asymmetric alkylation reaction, see: a) B. M. Trost, M. L. Crawley, Chem. Rev. 2003, 103, 2921 – 2943; b) B. M. Trost, J. Org. Chem. 2004, 69, 5813 – 5837.
37 The Tsuji-Trost Reaction: Strychnine a) S. D. Knight, L. E. Overman, G. Pairaudeau, J. Am. Chem. Soc. 1993, 115, 9293 – 9294b) S. D. Knight, L. E. Overman, G. Pairaudeau, J. Am. Chem. Soc. 1995, 117, 5776 – 5788.
38 The Tsuji-Trost Reaction: Roseophilin a) A. Fürstner, H. Weintritt, J. Am. Chem. Soc. 1998, 120, 2817 – 2825;b) A. Fürstner, T. Gastner, H. Weintritt, J. Org. Chem. 1999, 64, 2361 – 2366.
39 The Tsuji-Trost Reaction: Hamigeran B B. M. Trost, C. Pissot-Soldermann, I. Chen, G.M. Schroeder, J. Am. Chem. Soc. 2004, 126, 4480 – 4481.
40 The Tsuji-Trost Reaction: (+)-g-lycorane H. Yoshizaki, H. Satoh, Y. Sato, S. Nukui, M. Shibasaki, M. Mori, J. Org. Chem. 1995, 60, 2016 – 2021.
41 The Negishi CouplingThe use of organozinc reagents as the nucleophilic component in palladium-catalyzed cross-coupling reactions, known as the Negishi coupling, actually predates both the Stille and Suzuki processes, with the first examples published in the 1970s.However, the stunning progress in the latter procedures left the Negishi process behind, underappreciated and underutilised.Organozinc reagents exhibit a very high intrinsic reactivity in palladium-catalyzed cross-coupling reactions, which combined with the availability of a number of procedures for their preparation and their relatively low toxicity, makes the Negishi coupling an exceedingly useful alternative to other cross-coupling procedures, as well as constituting an important method for carbon–carbon bond formation in its own right.a) E. Negishi, A. O. King, N. Okukado, J. Org. Chem. 1977, 42, 1821 – 1823; for a discussion, see: b) E. Negishi, Acc. Chem. Res. 1982, 15, 340 – 348.a) E. Erdik, Tetrahedron 1992, 48, 9577 – 9648; b) E. Negishi, T. Takahashi, S. Babu,D. E. Van Horn, N. Okukado, J. Am. Chem. Soc. 1987, 109, 2393 – 2401.
43 The Negishi Coupling: Discodermolide a) A. B. Smith III, T. J. Beauchamp, M. J. LaMarche, M. D. Kaufman, Y. Qiu, H. Arimoto, D. R. Jones, K. Kobayashi, J. Am. Chem. Soc. 2000, 122, 8654 – 8664;b) A. B. Smith III, M. D. Kaufman, T. J. Beauchamp,M. J. LaMarche, H. Arimoto, Org. Lett. 1999, 1, 1823 – 1826.c) For a review of the chemistry and biology of discodermolide, see: M. Kalesse, ChemBioChem 2000, 1, 171 – 175d) For examples of other approaches to discodermolide, see: I. Paterson, G. J. Florence, Eur. J. Org. Chem. 2003, 2193 – 2208.e) In the synthesis of discodermolide by the Marshall group, a B-alkyl Suzuki–Miyarua fragment-coupling strategy was employed to form the C14C15 bond, in which 2.2 equivalents of an alkyl iodide structurally related to 309 was required: J. A. Marshall, B. A. Johns, J. Org. Chem. 1998, 63, 7885 – 7892.
44 The Negishi Coupling: Amphidinolide T1 a) C. Aïssa, R. Riveiros, J. Ragot, A. Fürstner, J. Am. Chem. Soc. 2003, 125, –
45 The Fukuyama CouplingThe Fukuyama Coupling is a modification of the Negishi Coupling, in which the electrophilic component is a thioester.The product of the coupling with a Negishi-type organozinc reagent is carbonyl compound, thus negating the need for a carbon monoxide atmosphere.H. Tokuyama, S. Yokoshima, T. Yamashita, S.-C. Lin, L. Li, T. Fukuyama, J. Braz. Chem. Soc., 1998, 9,
46 Palladium Catalysis: Outlook And Summary This review has highlighted only a small number of applications of palladium catalysis in organic synthesis, but new examples are published every month.Each example pushes the field forwards, towards universal conditions, where application of them results in a useful yield without prior optimisation.However, palladium is only one metal; the breadth of catalysis available from rhodium, ruthenium and platinum based systems extend far further, and into the realms of metathesis. Fürstner has shown analogous procedures using Iron catalysts, with obvious economic and toxicity benefits.For an example of palladium-mimicking rhodium catalysis, see: M. Lautens and J. Mancuso, Org. Lett. 2002, 4, 2105For a recent review of "atom ecconomic" ruthenium catalysis, see: B. M. Trost, M. U. Frederiksen, M. T. Rudd, Angew. Chem. Int. Ed., 2005, 41, 6630 – 6666.For the complementary review on Metathesis Reactions in Total Synthesis, see: K. C. Nicolaou, P. G. Bulger, D. Sarlah , Angew. Chem. Int. Ed., 2005, 41,A. Fürstner, R. Martin, Chem. Lett. 2005, 34,