Stereoselectivity stoichiometric chiral reagents

E. Stereoselective Cyclopropanation of Alkenes using Stoichiometric Chiral Reagents... 

In all three of the above-mentioned chiral transformations, stoichiometric amounts of enantiomerically pure compounds are required. An important development in recent years has been the introduction of more sophisticated methods that combine the elements of the first-, second-, and third-generation methods and involve the reaction of a chiral substrate with a chiral reagent. The method is particularly valuable in reactions in which two new stereogenic units are formed stereoselectively in one step (Fig. 1-30, 4). 

The aldol reaction is one of the most useful carbon-carbon bond forming reactions in which one or two stereogenic centers are constructed simultaneously. Diastereo-and enantioselective aldol reactions have been performed with excellent chemical yield and stereoselectivity using chiral catalysts [142]. Most cases, however, required the preconversion of donor substrates into more reactive species, such as enol silyl ethers or ketene silyl acetals (Scheme 13.45, Mukaiyama-type aldol addition reaction), using no less than stoichiometric amounts of silicon atoms and bases (Scheme 13.45a). From an atom-economic point of view [143], such stoichiometric amounts of reagents, which afford wastes such as salts, should be excluded from the process. Thus, direct catalytic asymmetric aldol reaction is desirable, which utilizes unmodified ketone or ester as a nucleophile (Scheme 13.45b). Many researchers have directed considerable attention to this field, which is reflected in the increasing... 

Asymmetric catalytic osmylation.s Chiral cinchona bases are known to effect asymmetric dihydroxylation with 0s04 as a stoichiometric reagent (10, 291). Significant but opposite stereoselectivity is shown by esters of dihydroquinine (1) and of dihydroquinidine (2), even though these bases are diastereomers rather than enantiomers. 

Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

In a lithium amide promoted deprotonation, one lithium amide molecule is consumed for each deprotonated epoxide molecule. Since chiral hthium amides are expensive reagents, there is a strong desire to develop less costly synthetic procedures for stereoselective deprotonations. Catalysis has the potential to solve the problem. What are needed are bulk bases capable of regenerating the chiral hthium amide from the chiral diamine produced in the deprotonation reaction. There have been some attempts along this line, e.g., by Asami and co-workers, who used the non-chiral hthium amide LDA as bulk base and the chiral hthium amide 4 as catalyst [9,12,39-41]. However, the stereoselectivity was considerably lower than what had been achieved in absence of the bulk base, i.e., under stoichiometric conditions. Most likely, the decreased stereoselectivity in the presence of bulk LDA is due to competing deprotonation by LDA to yield racemic product alcohol. The situation is illustrated in Scheme 9. 

Reagent-controlled stereoselective halogenation refers to the use of a stoichiometric amount of promoter to induce the stereoselective halogenation. To date, the reagent-controlled approaches have hmited examples in the synthesis of chiral bioactive organohalogens and related skeletons. Some recent examples will be described in this section. 

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