Enantioselective Organocatalyzed Bromolactonizations: Applications in Natural Product Synthesis

Asymmetric bromolactonization reactions of delta-unsaturated carboxylic acids have been investigated in the presence of 10 chiral squaramide hydrogen-bonding organocatalysts. The best catalyst enabled the cyclization of several 5-arylhex-5-enoic acids into the corresponding bromolactones with up to 96% ee and in high to excellent chemical yields. The reported catalysts are prepared in a straightforward manner in two steps from dimethyl squarate. The utility of the developed protocol was demonstrated in highly enantioselective syntheses of the sesquiterpenoids (-)-gossoronol and (-)-boivinianin B. Both natural products were obtained in >= 99% enantiomeric excess.