Selectivity Switch in a Rhodium(II) Carbene Triggered Cyclopentannulation: Divergent Access to Three Polycyclic Indolines

Abstract

A selectivity switch in a RhII/carbene‐triggered cyclopentannulation with catalytic InCl3 is reported for the first time, affording both diastereomers of the fused spiroindolines and an unusual bridged tetracyclic indoline in high yields with excellent selectivities. Mechanistic studies indicate an intramolecular annulation of the indole with an in situ formed aminocyclopropane. The stepwise thermal conversions from the kinetic spiroindoline to the metastable bridged indoline, and then to the thermodynamic spiroindoline, involving a ring‐opening rearrangement of a cyclopentane, is crucial for selectivity control.

Catalytic (3 + 2) annulation of donor–acceptor aminocyclopropane monoesters and indoles

“…When an intramolecular reaction was performed with aminocyclopropane 1n, the desired product 5h was obtained in >95 : 5 dr, but with another relative conguration (supported by NOESY experiments, see ESI †), in agreement with the results reported by Tang and coworkers using aminocyclopropane diesters. 16 We further performed the reaction with 1 mmol of aminocyclopropane 1d with protected indoles 2b-d and obtained similar yields and dr (Scheme 5). With 2a, a further scale up to 1.00 g (3.36 mmol) was done, giving 4a in 90% yield and 93 : 7 dr. Aer reduction of the ester on 4c with DIBALH, the tosyl group was removed using reductive naphthalene/lithium conditions leading to amino alcohol 6.…”

“…When an intramolecular reaction was performed with aminocyclopropane 1n , the desired product 5h was obtained in >95 : 5 dr, but with another relative configuration (supported by NOESY experiments, see ESI † ), in agreement with the results reported by Tang and co-workers using aminocyclopropane diesters. 16 …”

“…7 d Recently, Tang and co-workers described the in situ formation of unstable tosyl-protected aminocyclopropane diesters and their use in intramolecular annulation with indoles leading to tetracyclic indolines ( Scheme 2b ). 16 By comparison, arylcyclopropyl ketones 7 d and alkoxycyclopropyl monoesters 8 b gave annulation products in good yields, but these methods are not catalytic and are limited to the synthesis of tertiary stereocenters at the acceptor position ( Scheme 2c ). Low diastereoselectivities are obtained for several substitution patterns and in the case of alkoxycyclopropanes, annulation was successful only for C3-unsubstituted indoles.…”

Alleviating Catalyst Decay Enables Efficient Intermolecular C(sp3)–H Amination under Mechanochemical Conditions

“…This designer complex merges two carboxylate ligands through an appropriately spaced linker to confer added structural stability and prevent ligand disassociation . The marked repertoire of this catalyst has delineated an array of nitrene and carbene transfer reactions since its advent. − To test its viability under mechanochemical conditions, substrate 1a tethering a polar amide was chosen in combination with 2,2,2-trichloroethyl sulfamate (TcesNH 2 ) 2a and PhI­(OAc) 2 . The reaction was performed in a stainless steel jar containing stainless steel balls (5.0 diameter) in a Mitrcn Planetary Mill.…”

A Synthesis of Multifunctionalized Indoles from [3 + 2] Annulation of 2-Bromocyclopropenes with Anilines

“…The vinylic carbon atoms of cyclopropene are sp 1.19 hybridized, indicating that the cyclopropane sometimes could serve as an alkyne equivalent. With continuing effort and interest in the field of both indole derivatives and small ring compounds, in this study, we have developed an unexpected synthesis of 2,3-disubstituted indoles from [3 + 2] annulation of donor–acceptor cyclopropenes , with anilines, which displays different regioselectivity, compared with the Larock indole synthesis, for the larger diester moiety to be installed at the 3-position and the smaller aryl group to be placed at the 2-position of indole (eq b, Scheme ). In the presence of nickel­(II) as the catalyst, various multifunctionalized indoles were furnished in up to 86% yield with excellent regioselectivities.…”