Development of a new reaction system for the synthesis of highly opticallyactive alpha,gamma-substituted gamma-butyrolactones

A highly useful method for the synthesis of optically active alpha,gamma -s ubstituted gamma -butyrolactones has been developed. The SmI2-induced reduc tive coupling of chiral 2-alkyl acrylates derived from isosorbide with keto nes in the presence of (1S)-(-)-2,10-camphorsultam as a proton source give the chiral alpha,gamma -substituted gamma -butyrolactones in good yields an d high enantiomeric purities (up to > 99% ee for trans and 75% ee for cis). The reaction system has been investigated with various ketones, and it is demonstrated that this system is very effective for trans-alpha,gamma -subs tituted gamma -butyrolactones. Both the chiral auxiliary and the hindered p roton source in this system are necessary for the observed excellent ee val ues of the products. The absolute configuration of the trans products is as signed on the basis of the X-ray crystal structure.