ENANTIOMERICALLY PURE KETALS - DIASTEREOFACIAL SELECTIVITY IN THE HALOGENATION OF ENOL ETHERS

(2R,3R)- and (2S,3S)-Tartaric acids are often used as chiral auxiliaries in directing asymmetric functionalization of prochiral olefins.1-3 For example, the electrophilic bromination of tartrate ketals constitutes the key step (Scheme I) in the industrial asymmetric synthesis of (S)-(+)-2-(6-methoxy-2-naphthyl)propanoic acid (Na-proxen).ld,eThe diastereoselectivity of the bromination depends upon the geometry of the enol ether and the diastereofacial selectivity of attack on the enol ether. The lack of information on the stereochemical integrity and composition of the enol ether(s) 4 (Scheme II) forms a major deficiency in providing a mechanistic understanding. Studying enol ethers of defined geometry provides an opportunity to explore the question of diastereofacial selectivity induced by a chiral auxiliary. The present paper reports that halogenating ketals 5 {n = 1) and 6 (n = 0), where the corresponding enol ethers are constrained to a single geometry, produces unprecedently high diastereo-selective chlorination and iodination as well as bromination (Scheme III). © 1990, American Chemical Society. All rights reserved.