Abstract
A general method for total synthesis of natural trisubstituted γ-lactones is developed on the basis of the chemistry of alkynyltungsten compounds. The key step in this approach involves the cycloalkenation of tungsten-η 1 -(3R,4S)-pent-1-yne-3,4-diol with aldehydes to give tungstenoxacarbenium salts, further leading to 3-alkylidene-4-hydroxy-5-methyl-γ-lactones upon demetalation. This synthetic sequence proceeds well for alkynylaldehydes and the MOM derivative of tungsten-η 1 -(3R,4S)-pent-1-yne-3,4-diol. The resulting butyrolactone products are transformed into natural trisubstituted butyrolactones including (+)-blastmycinone, (+)-blastmycinolactol, (+)-antimycinone, NFX-2, and (+)-isodihydromahubanolide A. By using the same approach based on (R)-ethyl lactate, the natural (-)-litsenolide C 1 can be prepared in a few steps.