Stereocontrolled Syntheses of Piperidine Derivatives Using Diastereoselective Reactions of Chiral 1,3-Oxazolidines with Grignard Reagents: Asymmetric Syntheses of the Pinidine Enantiomers.

Pinidine is the main constituent of Pinus sabiniana and related plant species as determined, along with its chemical structure, by Tallent and co-workers over 40 years ag0.1 The complete stereochemistry of pinidine was unambiguously established by Hill to be la, usmg chemical and spectroscopic methods.2 Very recently, further work on the pinidine alkaloid contents of pine (Pinus) and spruce (Picea) trees and a biosynthetic hypothesis were put forurard by Stermitz and co-workers.3 They also revealed striking evidence of the toxic and teratogenic activities of pinidine that might be responsible for premature parturition or fetal abortion in pregnant range cows that consume the needles of Pinus ponderosa (Ponderosa pine). The first total synthesis of pinidine was accomplished by Leete via resolution of a racemic mixture.4' A further synthesis of the racemate4b and six enantiospecific routes to la and the unnatural enantiomer lb starting from (S.S)-tartaric acid,5* (R.R)-tartaric acid,ba (S)-ethyl lactate,5b