Asymmetric synthesis of (R)-(−)-carnitine

A TiCl4-promoted Mukaiyama-type aldol reaction of the ketenesilyl acetal of ethyl acetate with the lactone carbonyl of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (1) proceeds with a high degree of diastereoselectivity. The TBDMS-protected hemiketal thus obtained was efficiently converted into highly enantiomerically enriched (R)-(−)-carnitine by following an elimination–reduction protocol. This approach further demonstrates the utility of commercially available glycine template 1 as a potential substrate for the asymmetric synthesis of both enantiomers of carnitine.