Synthesis of Chiral γ-Lactones by One-Pot Sequential Enantioselective Organocatalytic Michael Addition of Boronic Acids and Diastereoselective Intramolecular Passerini Reaction

The synthesis of alpha,gamma-substituted chiral gamma-lactones was quickly achieved in a one pot sequential process. The procedure involves an enantioselective organocatalysed transfer of boronic acid to 5-hydroxyfuran-2(5H)-one, followed by an intramolecular diastereoselective Passerini-type reaction. The methodology was developed and optimized with N-Boc-indole-2-boronic acid giving access to alpha-indole-gamma-substituted lactones in high yields and good diastereoisomeric and enantiomeric ratios. By applying the process to other boronic acids, the synthesis of structurally diversified alpha,gamma-substituted chiral lactones was also achieved in good yields albeit with lower enantioselectivities.