Highly diastereoselective alkylation, acylation and aldol condensation of cis- and trans-(N-acyloyl)hexahydrobenzoxazolidin-2-ones

The potential of hexahydrobenzoxazolidinones 1a-d as chiral auxiliaries was explored. N-Acylation of 1a-d, 2a-d and 3a-d was followed by methylation a nd benzylation via the corresponding sodium enolates generated by treatment with NaHMDS. Diastereoselectivities of 98% or higher were observed. The ab solute configuration of the newly created stereogenic center was establishe d by chemical correlation with 2-benzyl-1-propanol. The stereochemical resu lts are congruent with addition to the electrophile from the less hindered face of a (Z)-configured enolate, the sodium cation being coordinated by bo th carbonyl oxygens of the substrate. cis- and trans-hr-Propionyl derivativ es 2a-d were treated with Bu2BOTf/Et3N to give dialkylboron enolates 6a-d, which were then reacted with acetaldehyde and benzaldehyde. H-1 and C-13 NM IR analyses showed the formation of a single diastereomeric aldol addition product, whose relative configuration was ascertained as syn from the measu rement of the (3)J(H(2')/(3')) coupling constants, and whose absolute confi guration was determined by X-ray crystallographic analysis. The results are rationalized in terms of a Zimmerman-Traxler transition state, with a (Z)- configured enolate where boron is coordinated to the aldehyde carbonyl rath er than the oxazolidinone carbonyl. Substrate 2a was also reacted with acyl chlorides via the sodium enolate (NaHMDS). The effect of reaction conditio ns on O-versus C-acylation, as well as the influence of solvent and additiv es on diastereoselectivity, are discussed. (C) 2001 Elsevier Science Ltd. A ll rights reserved.