Stereospecific Synthesis of α- and β-Hydroxyalkyl P-Stereogenic Phosphine-Boranes and Functionalized Derivatives: Evidence of the PO Activation in the BH3-Mediated Reduction

Access to hydroxy‐functionalized P‐chiral phosphine–boranes has become an important field in the synthesis of P‐stereogenic compounds used as ligands in asymmetric catalysis. A family of optically pure α and β‐hydroxyalkyl tertiary phosphine–boranes has been prepared by using a three‐step procedure from readily accessible enantiopure adamantylphosphinate, obtained by semi‐preparative HPLC on multigram scale. Firstly, a two‐step one‐pot transformation affords the enantiopure hydroxyalkyl tertiary phosphine oxides in good yields and enantioselectivities. The third step, BH3‐mediated reduction, allows the formation of the desired phosphine–boranes with excellent stereospecifity. The mechanistic study of this reduction provides new evidence to elucidate the crucial role of the pendant hydroxy group and the subsequent activation of the PO bond by the boron atom. Control of the P‐stereogenic center: Optically pure α‐ and β‐functionalized hydroxy phosphine oxides were prepared in one pot from enantiopure phosphinate. Their stereospecific BH3‐mediated reduction was studied by vibrational circular dichroism, chiral HPLC, and XRD to assess the absolute configuration of the chiral centers, as well as the retention or inversion processes. The role of BH3 as PO bond activator was also clearly identified by NMR studies.