Stereoselective access to polypropionates expedited by the double hydroboration of allenes: Total synthesis of antitumor (−)-pironetin

Abstract

Polyketides, a large class of secondary metabolites, have been of long-standing interest to the synthetic community due to their intriguing biological activities and structural versatility and complexity. A typical structural unit of various natural products, polypropionate, has prompted enormous efforts in the development of novel synthetic methods and strategies in the past five decades. In this study, a non-aldol-type approach based on double hydroboration of allenes has been developed to provide a powerful method for the stereodivergent construction of various polyol stereotriads and stereotetrads that are amenable for synthesizing polypropionates. The stereochemical control is possibly attributable to the boronate complex that aligned itself as a rigid conformation for the second stereoselective hydroboration reaction by suppressing the barotropic rearrangement of allylborane intermediates. The feasibility of preparing the key polypropionate motif facilitates the efficient synthesis of (-)-pironetin, a potent α-tubulin inhibitor halting the cell cycle at M phase.