Synthesis of Indole-Fused Bicyclo[3.1.1]heptanes through (3+3) Cycloaddition of 2-Indolylmethanols with Bicyclo[1.1.0]butanes

A variety of indole-fused bicyclo[3.1.1]heptanes were prepared in good yields with high regioselectivity through organocatalyzed umpolung (3+3) cycloaddition of 2-indolylmethanols and bicyclo[1.1.0]butanes (BCBs) under mild reaction conditions. Control experiments revealed that both the Brønsted acid catalyst and hexafluoroisopropanol (HFIP) played important roles in the (3+3) cycloaddition and the addition of HFIP can reduce the production of byproducts. More importantly, a high diastereoselectivity of indole-fused bicyclo[3.1.1]heptane was obtained. The present method features gram scale preparation, umpolung of position C3 of indole, cooperative Brønsted acid- and HFIP-catalyzed (3+3) cycloaddition of BCBs, and diverse types of 3D tetrahydrocarbazole scaffolds.