A Catalytic Diastereoselective Formal [5+2] Cycloaddition Approach to Azepino[1,2‐a]indoles: Putative Donor–Acceptor Cyclobutanes as Reactive Intermediates

Abstract

A catalytic formal [5+2] cycloaddition approach to the diastereoselective synthesis of azepino[1,2-a]indoles is reported. The reaction presumably proceeds through a Lewis acid catalyzed formal [2+2] cycloaddition of an alkene with an N-indolyl alkylidene β-amide ester to form a donor-acceptor cyclobutane intermediate, which subsequently undergoes an intramolecular ring-opening cyclization. Azepine products are formed in up to 92% yield with high degrees of diastereoselectivity (up to 34:1 d.r.).

Bio‐Inspired Fragmentations: Rapid Assembly of Indolones, 2‐Quinolinones, and (−)‐Goniomitine

“…Avariety of readily available 2-alkynyl-anilines 1 and a-diazo ketones 2 proved to be efficient substrates for the cascade reactions,furnishing the indolones 4 in modest to good yields.T he electron-withdrawing groups (EWG), which were essential for the reactions to occur, could be varied, and thus different functional groups were introduced into the products (4a-c). Thes ubstituted indolones (4d-g, 4i)w ere assembled with good efficiencyt racing back to the readily available a-diazo ketones 2.B oth hydro-azepino[1,2-a]indolones (4a-g) [10] and hydropyrido[1,2-a]indolones (4h,i)w ere successfully prepared by the telescoped one-pot reactions.In addition, products with halogen synthetic handles on the benzene ring could also be prepared (4j, 4k).…”

Thrilling Strain! Donor–Acceptor‐Substituted Cyclobutanes for the Synthesis of (Hetero)Cyclic Compounds

“…An elegant route to azepino[1,2-a]indoles 21 with D-A cyclobutanes 20 as intermediates was recently published by France and co-workers [10] (Scheme 4). Alkenes 19 and styrene derivatives 18 were expected to lead to cyclobutanes 20, and with zinc bromide as a mild Lewis acid the anticipated [2+2] cycloadducts 20 were indeed obtained, but roughly the same quantity of product 21 was also isolated.…”

The Catalytic, Formal Homo‐Nazarov Cyclization as a Template for Diversity‐Oriented Synthesis

“…Inspired by our previous work and as a starting point, we envisioned a Lewis acid‐catalyzed approach involving intramolecular ring‐opening cyclizations of N ‐indolyl malonamide‐derived cyclobutanes 85 to access the azepino[1,2‐ a ]indole core 86 (Scheme ) . We sought to prepare the desired cyclobutanes using Lewis acid‐promoted formal [2+2] cycloadditions of the N ‐indolyl α‐alkylidene malonamides 87 with alkenes 88 .…”