Synthesis of (-)-octalactin a by a strategic vanadium-catalyzed oxidative kinetic resolution.

The kinetic resolution of racemic material is a well-established approach used to prepare a wide range of enantiomerically enriched compounds. However, the overall efficiency of a standard kinetic resolution is limited to a maximum theoretical yield of 50% of the enriched chiron, with the balance of undesired material being discarded in most applications. As a result of this inherent overall efficiency, kinetic resolution is often deemed unacceptable on a preparative scale except for the most simple and inexpensive of substrates. Consequently, kinetic resolution methods, especially in the context of complex molecule synthesis, have largely been relegated to the preparation of small chiral building blocks at an early stage of the synthesis. Having recently developed a vanadium-catalyzed asymmetric aerobic oxidation of a hydroxycarbonyl compounds, we became interested in exploring the potential of this kinetic resolution methodology, to move beyond the preparation of simple building blocks toward a more meaningful, strategic synthetic function. The observation that asymmetric oxidation of substrates bearing multiple stereocenters by catalytic amounts of [VO(OiPr)3] and (S)-2-(3,5-di-tert-butylsalicylideneamino)-tert-butyl-1-ethanol (1) resulted in the isolation of both enantioenriched alcohol and ketone products motivated us to consider a synthetic strategy (Figure 1) wherein