Asymmetric Synthesis of α-Methylene-γ-Butyrolactones via Tandem Allylboration/Lactonization: a Kinetic Resolution Process

Abstract

The α-methylene-γ-butyrolactone motif is a widely encountered unit in many natural products and pharmaceutical compounds. Herein, a practical and efficient synthesis of α-methylene-γ-butyrolactones from readily available allylic boronates and benzaldehyde derivatives was developed with chiral N,N′-dioxide/AlIII complex as the catalyst. The key success of this transformation was the kinetic resolution of allylboration intermediate via asymmetric lactonization. This protocol enabled to assemble all of four stereoisomers from the same set of starting materials upon variable lactonization. Taking advantage of the current method as the key step, catalytic asymmetric total synthesis of eupomatilones 2, 5, and 6 was accomplished. Control experiments were carried out to probe into the tandem reaction as well as the origin of stereoselectivities.