Synthesis of Indole-Fused Bicyclo[3.1.1]heptanes through (3+3) Cycloaddition of 2-Indolylmethanols with
Cheng-Jing Li1, Hai-Fang Lin1, Hai-Min Hu1
1Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, University Engineering Research Center for Chemistry of Characteristic Medicinal Resources (Guangxi), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin 541004, China.
Abstract:
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.
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