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Highly Diastereo‐ and Enantioselective Synthesis of Cyclohepta[ b ]indoles by Chiral‐Phosphoric‐Acid‐Catalyzed (4+3) Cycloaddition
Author(s) -
Gelis Coralie,
Levitre Guillaume,
Merad Jérémy,
Retailleau Pascal,
Neuville Luc,
Masson Géraldine
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201807069
Subject(s) - cycloaddition , enantioselective synthesis , phosphoric acid , carbocation , catalysis , chemistry , derivatization , combinatorial chemistry , organic chemistry , high performance liquid chromatography
A highly enantio‐ and diastereoselective formal (4+3) cycloaddition of 1,3‐diene‐1‐carbamates with 3‐indolylmethanols in the presence of a chiral phosphoric acid catalyst is reported. The approach described herein provides efficient access to 6‐aminotetrahydrocyclohepta[b]indoles in good yields with mostly complete diastereoselectivity and excellent levels of enantioselectivity (>98:2 dr and up to 98 % ee). Mild reaction conditions, facile scale‐up, and versatile derivatization highlight the practicality of this methodology. A mechanistic study suggests that cycloaddition occurs in a stepwise fashion, after the formation of an ion pair between the chiral catalytic phosphate and the intermediate carbocation.