Chiral auxiliary-induced asymmetric synthesis of (R)- and (S)-Garner’s aldehydes

This article describes the synthesis of optically pure four N-Boc and N-Cbz-protected (R)- and (S)-isomers of Garner's aldehyde. The key step involves TiCl4-catalyzed Evans' aldol reaction of the uncommon chiral synthon "glycine enolate equivalent" of N-(N-Boc/Cbz-glycinyl) oxazolidinone with gaseous formaldehyde. The chromatographically separable Evans and non-Evans adduct formation takes place through the installation of hydroxymethyl functionality on chiral glycine enolate in good yields. The orthogonality of the reaction was maintained via the "reverse addition" in the aldol reaction on Evans chiral auxiliary. This method provides a promising opportunity for the synthesis of expensive (R)-Garner's aldehyde evading the use of unnatural d-serine. Moreover, asymmetric alkylation of Li-enolate of N-(N-Boc-glycinyl) oxazolidinone is a promising opportunity for the formation of an exclusive single isomer of (R)-Garner's aldehyde.