有机合成化学第六章

C=O
+ -
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Organometallic Species
Organometallic units give a polarization reversal known as umpolung with the negative charge on the carbon and of course the positive charge on the metal
Richard Heck
根岸 英一 Ei-ichi Negishi
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John Kenneth Stille
John was born in Tucson, AZ, on May 8, 1930. He received his B.A. and M.A. degrees in Chemistry at the University of Arizona and his Ph.D. with Carl Marvel at the University of Illinois. Between earning his M.A. and Ph.D. degrees John served in the Navy during the Korean War. he began his professional career in 1957 as a member of the faculty of the University of Iowa. John Stille died on July 19,1989, in the crash of the United Airlines flight in Sioux City, IA.
Synthetic Organic Chemistry
合成化学
Lecture 06 Palladium-Catalyzed Cross Couplings Dr. Shouyun Yu 俞寿云 副教授
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Reading Assignment
Negishi, E. I. Acc. Chem. Res. 1982, 15, 340. Stille, J. K. Angew. Chem. Int. Ed. 1986, 25, 508. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (cited: 6063) Suzuki, A. J. Organomet. Chem. 1999, 576, 147. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009. Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359. Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633. Nicolaou, K. C.; et al, Angew. Chem. Int. Ed. 2005, 44, 4442. Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874. Yu, J. Q. et al, Angew. Chem. Int. Ed. 2009, 48, 5094. Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
K. Fagnou, et al, Science, 2007, 316, 1172.
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Nobel Prize in Chemistry 2010
"for palladium-catalyzed cross couplings in organic synthesis"
铃木 章 Akira Suzuki
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Pd-Catalyzed Cross Couplings
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Reaction Parameters
♣ Organometallics: M can be B, Sn, Zn, Si, Mg, Zr…… ♣ Halides or pseudohalides: X can be Cl, Br, I, OTf, OTs, OAc… ♣ R1 and R2: the best results are always obtained for SP2 carbons then SP carbons–SP3 do work in some cases, but have many problems. ♣ Catalysts: the most common transition metal catalyst is palladium, as either Pd(0) or Pd(II). Some other metals, such as Ni, Rh, Ru, Cu, Fe, Au, do work in some cases. ♣ Ligands: The most common ligands are phosphine ligands which can coordinate to metals to stabilize them and dissociate from metals to activate them.
More active, less selective!
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Preparation of Organometallics
Direct metallation using the alkali metals (e.g., Li) is rather vigourous and dangerous, however, using magnesium is safe and usually works well.
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Cross Couplings
♣ Organotins (known as Stille reaction) have proved to be extremely successul, including a wide range of aryl, alkenyl, alkynyl and even alkyl units give successful results, generally, organotins, like organoborons can be isolated, stored and used when required, but organotins are extremely toxic.
Many transmetallations can begin from the Grignard reagent which is relatively easily prepared through direct metallation, and yet is not dangerous.
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Stille (1930-1989)
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In memory of John Kenneth Stille Robert W. Lenz Macromolecules, 1990, 23, 2417.
Pd-Catalyzed Cross Couplings
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Pd-Catalyzed Cross Couplings
Many simple lithium reagents are commercially, as well as many simple Grignard reagents.
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Preparation of Organometallics
Transmetallation - the reaction of a more reactive Organometallic with a halide or ester of another metal to generate the new (less reactive) organometallic species
Cross CoБайду номын сангаасplings
♣ Organolithiums are far too reactive. ♣ Organomagnesiums (known as Kumada reaction) work due to a high reactivity, but suffer from undesired homo-coupled products, poor yields and low tolerance to functional groups such as carbonyl, ester and nitrile. ♣ Organozincs (known as Negishi reaction) are less electropositive and so have a lower reactivity and so less homo-coupling they also tolerate a wider range of functional groups than Grignards such as carbonyl, ester and nitrile.
Lu, Z.; Ma, S. M. Angew. Chem. Int. Ed. 2008, 47, 258.
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Biaryl Compounds
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Strategies for Biaryl Compounds
Keith Fagnou (1971-2009) @ University of Ottawa died of complications resulting from a H1N1 influenza infection on November 11, 2009 at the age of 38
Organometallics such as potassium, sodium and lithiums are extremely dangerous to any sources of moisture; Grignard reagents, organozincs, organocoppers and organomanganese compounds are still moisture sensitive, but not dangerously.
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Organometallic Species
Metals, which are electropositive, and hence renders a negative charge on the carbon atom – which can then – in theory react with one of a vast range of carbon positive species generating a carbon-carbon bond.
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Reading Assignment
Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1. Denmark, S. E.; Fu, J. P. Chem. Rev. 2003, 103, 2763. Kennedy, J. W. J.; Hall, D. G. Angew. Chem. Int. Ed. 2003, 42, 4732. Trost, B. M. J. Org. Chem. 2004, 69, 5813. Mohr, J. T.; Stoltz, B. M. Chem.-Asian J. 2007, 2, 1476.
♣ Organoborons (known as Suzuki reaction) have also proved to be extremely successful in much the same way as organotins, but organoborons do offer other advantages in terms of better tolerance to sterically hindered coupling sites and a lack of toxicity.