Enantioselective, Aerobic Copper-Catalyzed Intramolecular Carboamination and Carboetherification of Unactivated Alkenes

Abstract

Reduction of waste is an important goal of modern organic synthesis. We report herein oxidase reactivity for enantioselective intramolecular copper-catalyzed alkene carboamination and carboetherification reactions where previously used stoichiometric MnO2 has been replaced with oxygen. This substitution was risky as the reaction mechanism is thought to involve C–C bond formation via addition of alkyl carbon radicals to arenes. Such intermediates are also susceptible to C–O bond formation via O2 addition. Control of absolute stereochemistry under aerobic conditions was also uncertain. The oxidative cyclization efficiencies appear to track with the ease of the radical addition to the arenes.

Copper-catalyzed aerobic oxidative radical alkoxycyclization of tryptamines to access 3-alkoxypyrroloindolines

“…Combining with the previous reports about copper-catalyzed carboamination, 10 alkoxylation 12 of alkene, a possible reaction pathway is proposed in Scheme 3 . Initially, a ligand–exchange reaction of Cu( ii ) species with substrate 1a proceeds to form the chelation intermediate A.…”

“…Copper( ii )-promoted radical intramolecular carboamination of alkene has proven to be an effective means toward the synthesis of N-fused heterocycles. 10 Recent reports have utilized this strategy toward the cyclization and radical alkylation, aromatization and aminooxygenation of alkene. 10 However, due to the difficulty in homolytic breakage of the oxygen–hydrogen bond in alcohols with a high bond dissociation energy (BDE is ca.…”

“… 10 Recent reports have utilized this strategy toward the cyclization and radical alkylation, aromatization and aminooxygenation of alkene. 10 However, due to the difficulty in homolytic breakage of the oxygen–hydrogen bond in alcohols with a high bond dissociation energy (BDE is ca. 105 kcal mol −1 ), 11 the related direct cyclization and radical alkoxylation of carbon–carbon double bond with copper catalysts is still unknown.…”

Transition Metal‐Catalyzed Carboamination of Alkenes and Allenes: Recent Progress

“…An enantioselective intramolecular carboamination using copper triflate and bis(oxazoline) ligand was exemplified by Chelmer et al for the expedient synthesis of hexahydrobenzindoles (Scheme 43). [60] Reaction of various suitably substituted alkenyl amines 79 with 20 mol% of Cu(OTf) 2 and 22 mol% of bis(oxazoline) ligand furnished hexahydrobenz-indoles 86 in excellent yield and high enantio-and diastereoselectivity. The reaction pathway involved the formation of carbon radical Int-K, which on intramolecular trapping with aryl ring led to the formation of 86.…”

Heteroannulation of N-Fluoro-N-alkylsulfonamides with Terminal Alkynes via Remote C(sp3)–H Functionalization

“…However, replacement of the sulfonyl groups by a Bz or 2,4,6-trimethylbenzenesulfonate group resulted in no annulation reaction, probably due to the electronic and/or steric hindrance effect ( 3ea and 3ga ). Surprisingly, a general (4 + 2) annulation with aryl C­(sp 2 )–H bonds of the arylsulfonamide moiety, not with the remote C­(sp 3 )–H bonds, took place to access important 2 H -benzo­[ e ]­[1,2]­thiazine 1,1-dioxides 4oa–ra , when possessing an alkyl chain (e.g., 2-cyclopropylethyl, a propyl, or a butyl group) or a 3-phenylpropyl chain on the nitrogen atom. Encouragingly, the (3 + 2) annulation with the remote β–C­(sp 3 )–H bond occurred successfully to afford 3sa when using N -(2,2-diphenylethyl)­sulfonamide 1s .…”