Stereoselective Syntheses of Chiral Piperidines via Addition Reactions to 4-Pyridones

2 Stereoselective Syntheses of Chiral Piperidines via Addition Reactions to 4-Pyridones 

An alternative stereoselective synthesis of chiral heterocycles based on carbohydrate-induced stereodifferentiation includes nucleophilic addition reactions on heterocyclic systems already bound to the carbohydrate auxiliary. An example of this strategy has been shown by stereoselective addition of Grignard reagents to carbohydrate-linked 4-pyridones [61]. For this purpose, trimethylsiloxypyridine was glycosylated regioselectively using pivaloyl-protected glycosyl fluorides. 

This methodology opens up an efficient stereoselective access to chiral piperidi-none derivatives 60 which have opposite configuration compared to compounds 46 obtained by the tandem Mannich-Michael reaction sequence described in Section 4.3.2. The high diasteroselectivity and regioselectivity in these reactions once again illustrate the stereodifferentiating potential of carbohydrates in the synthesis of chiral heterocyclic systems. 

Carbohydrate-derived auxiliaries exhibit an efficient stereoselective potential in a number of nucleophilic addition reactions on prochiral imines. a-Amino acids, P amino acids and their derivatives can be synthesized in few synthetic steps, and with high enantiomeric purity. A variety of chiral heterocycles can readily be obtained from glycosyl imines by stereoselective transformations, providing evidence that carbohydrates have now been established as useful auxiliaries in stereoselective syntheses of various interesting classes of chiral compounds. 

115] M. J. Collins, R. J. Ferrier Monosaccharides, John Wiley Sons. New York, 1995. 

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