Catalytic and Enantioselective Halocarboxylative Cyclization of Unsaturated Alcohols using Chiral Bis(AMidine) Catalysts
Catalytic, enantioselective halocarboxylation of unsaturated alcohols was developed. Carbonic acid monoalkyl esters were prepared in situ as key intermediates through an equilibrium process under carbon dioxide atmosphere. N-Iodosuccinimide was added as an iodinating reagent and the reaction was kept at a low temperature to optimize enantioselectivity. Bis(AMidine)-based protic acid complexes were used to catalyze the reaction. The reactivity and selectivity were optimized by altering the reaction conditions: both lowered catalyst loading and temperature improved the desired enantiomeric excess (%ee) of the product, but it was achieved at the expense of lower yield; longer reaction time and the use of a solvent mixture, on the other hand, increased the conversion. Purification and characterization of the products were successfully carried out.