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

The synthesis of α,γ-substituted
chiral γ-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 α-indole-γ-substituted lactones in high yields
and good diastereoisomeric and enantiomeric ratios. By applying the
process to other boronic acids, the synthesis of structurally diversified
α,γ-substituted chiral lactones was also achieved in good
yields albeit with lower enantioselectivities.