Highly Diastereo- and Enantioselective Synthesis of Cyclohepta[ b ]indoles by Chiral-Phosphoric-Acid-Catalyzed (4+3) Cycloaddition

Coralie Gelis (1) , Guillaume Levitre (1) , Jérémy Merad (1) , Pascal ́ Retailleau (1) , Luc Neuville (1) , Géraldine Masson (1)

1 ICSN - Institut de Chimie des Substances Naturelles

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.

Domaines: Chimie organique; Catalyse

Coralie Gelis, Guillaume Levitre, Jérémy Merad, Pascal ́ Retailleau, Luc Neuville, et al.. Highly Diastereo- and Enantioselective Synthesis of Cyclohepta[ b ]indoles by Chiral-Phosphoric-Acid-Catalyzed (4+3) Cycloaddition. Angewandte Chemie International Edition, 2018, 57 (37), pp.12121-12125. ⟨10.1002/anie.201807069⟩. ⟨hal-02324701⟩