Organic synthesis catalytic asymmetric

The construction of strained three-membered ring systems remains a mainstay in organic synthesis. Catalytic asymmetric epoxidation and cyclo-propanation reactions continue to attract attention due to the inherent value of epoxides and cyclopropanes in pharmaceuticals and as synthons towards... 

In organic synthesis, modern asymmetric catalysis in particular, Pd can be more versatile [1-5] than Ni and Pt from the same group 10. The reason why Pd has become so useful is not easy to answer. However, one of the reasons stems from the favorable oxidation states of 0 and +2 (i.e., Pd(0) and Pd(II)). Pt, which is larger than Pd, can easily make coordinatively saturated octahedral Pt(IV) complexes with low catalytic activity. Ni, which is smaller than Pd, is apt to change its oxidation state to +1. Sometimes the Ni(I) complexes are not only too active as catalysts but also unstable for handling during the reactions. In turn, Pd, possessing an intermediate nature between those of Ni and Pt, has both the adequate stability and the suitable activity for a variety of catalyses. 

The development of new methods for the synthesis of enantioenriched molecules is a key area of modern organic chemistry. Catalytic asymmetric synthesis is one method by which enantioenriched compounds can be synthesised. A key class of... 

Catalytic Asymmetric Synthesis, VCH publishers New York, 1993 (d Noyori, R. Asymmetric Catalysis in Organic Synthesis, Wiley New York, 1994... 

See e.g. (a) W. Cahhuthehs, Cycloaddition Reactions in Organic Synthesis, Tetrahedron Organic Chemistry Series Vol. 8 Pergamon Press Elmsford, NY 1990 (b) I. OjiMA, Catalytic Asymmetric Synthesis, VCH Publishers. Inc. New York. 1993 ... 

Perhaps the most successful industrial process for the synthesis of menthol is employed by the Takasago Corporation in Japan.4 The elegant Takasago Process uses a most effective catalytic asymmetric reaction - the (S)-BINAP-Rh(i)-catalyzed asymmetric isomerization of an allylic amine to an enamine - and furnishes approximately 30% of the annual world supply of menthol. The asymmetric isomerization of an allylic amine is one of a large and growing number of catalytic asymmetric processes. Collectively, these catalytic asymmetric reactions have dramatically increased the power and scope of organic synthesis. Indeed, the discovery that certain chiral transition metal catalysts can dictate the stereo-... 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

Proceedings of the National Academy of Sciences of the United States of America, 101, 5347. (b) Ojima, I. (ed.) (2000) Catalytic Asymmetric Synthesis, 2nd edn, Wiley-VCH Verlag GmbH, New York, (c) Jacobsen, E.N., Pfallz, A. and Yamamoto, H. (eds) (1999) Comprehensive Asymmetric Catalysis, Springer, Berlin, (d) Noyori, R. (1994) Asymmetric Catalysis in Organic Synthesis, John Wiley Sons, Ltd, New York, (e) Drauz, K and Waldmann, H. (eds) (2002) Enzyme Catalysis in Organic Synthesis A Comprehensive Handbook,... 

Asymmetric hydrosilylation can be extended to 1,3-diynes for the synthesis of optically active allenes, which are of great importance in organic synthesis, and few synthetic methods are known for their asymmetric synthesis with chiral catalysts. Catalytic asymmetric hydrosilylation of butadiynes provides a possible way to optically allenes, though the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (2S,4S)-PPM turned out to be the best catalyst for the asymmetric hydrosilylation of butadiyne to give an allene of 22% ee (Scheme 3-20) [59]. 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

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