Nucleophilic additions on acetyldioxanes derived from (−)-(1R)-myrtenal used as chiral auxiliaries: substituent effects on the stereochemical outcome

Abstract

The synthesis of acetyldioxanes 4 and 9a starting from (−)-(1R)-myrtenal is described. The products were treated with a representative series of nucleophilic reagents (RMgX, RLi, NaBH₄ and LiAlH₄) to assess the effect of the substituent at C-3 on the stereochemical outcome. It was observed that the nucleophiles preferred the re-face of the CO group when the equatorial substituent at C-3 was a methyl group, whereas a phenyl group at the same position induced the addition through the si-face, thus allowing access to either desired stereochemistry of a final product. This behavior suggests that the formation of the expected Cram-chelated coordination complex takes a coplanar orientation with the C-3 equatorial substituent. Moreover, Grignard reagents were the most stereoselective nucleophiles. The stereochemistry of the addition was established by X-ray diffraction and chemical correlation.