Divergent Synthesis of α,γ-Disubstituted γ-Butyrolactones through Diastereoselective Bromolactonization with Alkali Metal Bromide: Asymmetric Total Synthesis of (+)-Dubiusamine C.

A divergent synthesis of α-substituted bromomethyl γ-lactones was developed, which involves the diastereoselective bromolactonization of α-substituted 4-pentenoic acids and 4-pentenamides via umpolung of bromide by use of alkali metal bromide and Oxone (potassium peroxymonosulfate mixture, 2KHSO5·KHSO4·K2SO4) to obtain mainly cis-products from α-substituted 4-pentenoic acids and trans-products from α-substituted 4-pentenamides, and it was found that the bromonium species generated from KBr and Oxone had higher activity than N-bromosuccinimide. Furthermore, the asymmetric total synthesis of (+)-dubiusamine C, which was isolated as a minor diastereomer from Pandanus dubius, was accomplished for the first time through the cis-selective bromolactonization of (S)-α-methyl-4-pentenoic acid in nine linear steps and 36% overall yield.