Reduction of Labeled Prochiral Carbonyl Compounds and Oximes

2 Reduction of Labeled Prochiral Carbonyl Compounds and Oximes 

The use of these reagents in the synthesis of enantiomeiicaUy enriched labeled derivatives is illustrated by the following examples. CBS reduction of 3 -bromo- and 3 -methoxy[carbonyl- C]acetophenones (33) with BH3 THF in the presence of 0.3 equivalents of iy -30b furnished (/ )-carbinols 34 in chemical yields of 75% and e.e.s of 97%. Subsequent Mitsunobu reaction with hydrazoic acid and reduction of the resulting 

The preparation of 22, starting material for a diastereoselective Evans auxiliary-promoted aldol reaction (see Section 11.3.2) and key intermediate in the synthesis of [ C]Sch 58235 (40). is an additional example of the compatibility of CBS reductions with a broad variety of substituents. Alcohol 22 was isolated after CBS reduction of ketone 2S with BH3 Me2S in the presence of 0.3 equivalents of ( )-2fia in nearly quantitative yield and 99% e.e. l 

The utility and equivalence of the alternative stoichiometric approach have been demonstrated with the enantioselective reduction of 41, a 4-aryl-4-oxo[l,4- C2]butanoic acid derivative, with (+)-Ipc2BCl to give (4/ )-hydroxyamide 42 in 80% radiochemical yield and 96% e.e. Further reduction with LiAlEL) converted 42 into (4/ )-[l,4- C2]ibutilide 1431. an antiarrhythmic agenf.  

Application of variant A to the reduction of anft-[rmg-U- C]acetophenone oxime methyl ether (55) afforded (S)-l-[ring-U- C]phenylethylamine 1561 in 70% radiochemical yield and 96% e.e.. In contrast to values published in the literature, enantiomeric excesses were only 80% when variant B was employed in the reduction of 3 -methoxy [carbonyl- C ] -acetophenone oxime methyl ether (57), so that the material had to be further purified through a diastereomeric salt.  

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