Access to Enantioenriched Spiro‐ϵ‐Lactam Oxindoles by an N‐Heterocyclic Carbene‐Catalyzed [4+3] Annulation of Flexible Oxotryptamines with Enals

Abstract

Oxotryptamines were firstly used as flexible four-atom synthons in an NHC-catalyzed formal [4+ +3] annulation, providing an ovel enantioselective method to access structurally diverse spiro-e-lactam oxindoles with excellent enantioselectivities.T his metal-free reactionf eatures ab road substrate scope, excellent functional-group tolerance and proceeds under mild reaction conditions. Importantly,e nantiopure privileged hexahydropyrroloindoles could be easily constructed by ao ne-pot process from the resulting spiro-e-lactam oxindoles.Scheme1.Constructiono fseven-membered rings promoted by NHC.

Recent advances of N-heterocyclic carbenes in the applications of constructing carbo- and heterocyclic frameworks with potential biological activity

“…They completed the [4 + 3] annulation by employing enals and oxotryptamines as substrates. 69 The reaction showed wide applicability to various aldehydes including aryl aldehydes, exible oxotryptamines 107.…”

Stereoselective synthesis and applications of spirocyclic oxindoles

“…More recent advances include Fu and Huang's NHC catalysed [4 + 3]-annulation of α,β-unsaturated aldehydes and amine substituted oxindoles (oxotryptamines, Scheme 83). 424 Song and Gong's previously discussed excellent Cu/NHC dual catalysis could be used with ethynyl benzoxazinanones to construct chiral azepines. 404…”

Recent Advances in Transition-Metal-Free (4+3)-Annulations

“…Fu and Huang developed a (4+3)-annulation reaction mediated by chiral 3.2.10NHC, where oxotryptamines 3.2.10a and enals 3.2.10b were coupled together in the presence of the stoichiometric oxidant 3.2.10[O] to give rise to enantioenriched spiro--lactam oxindoles 3.2.10c (Scheme 3.2.10). 62 This was the first time flexible oxotryptamines were employed to construct seven-membered heterocycles.…”