An L-phenylalanine-derived oxadiazinone: Its synthesis and efficacy as a chiral auxiliary in asymmetric aldol additions

ORGN 82

Delvis D. Dore, dddore@ilstu.edu and Shawn R. Hitchcock, hitchcock@xenon.che.ilstu.edu. Department of Chemistry, Illinois State University, Campus Box 4160, Normal, IL 61790
We have demonstrated in the past the utility of ephedrine- and norephedrine-derived oxadiazinones as chiral auxiliaries with asymmetric aldol additions. Our previous studies of these systems have shown that the C5 substituent position of these oxadiazinones directs the stereochemistry of the N4 position via intramolecular chiral relay, which in turn influences the approach of the aldehyde in titanium-mediated asymmetric aldol additions. We have synthesized an amino acid-derived auxiliary in an attempt to demonstrate its utility, as well as exhibit that the lack of a C6 substituent does not impede the nature of the C5 substituent. Through methodology developed by our group, L-phenylalanine was cyclized into (5R,4S)-4-isopropyl-5-benzyl-3,4,5,6-tetrahydro-2H-1,3,4-oxadizin-2-one and subsequently acylated with hydrocinnamoyl chloride in 79% yield. Reaction with benzyloxyacetaldehyde gave the aldol adduct in 49% yield and 19:1 diastereoselectivity, primarily as the syn-non-Evans adduct.