Ring Expansions of Activated Aziridines and Azetidines

Abstract

Facile construction of small and normal-sized, or more precisely, four to seven-membered aza-heterocyclic ring systems is always a challenging yet rewarding task for the synthetic organic chemists. Fortunately, activated aziridines and azetidines provide a direct and convenient access to this coveted molecular architectures through several elegant ring-expansion approaches. This chapter presents some of the illustrative and contemporary examples to demonstrate the synthetic diversity and efficiency of the ring-expansion strategies of activated aziridines and azetidines towards a vast array of small to normal-sized aza-heterocyclic moieties.

Catalyst-Free Visible-Light-Mediated Iodoamination of Olefins and Synthetic Applications

“…Notably, analogous chloroamination protocols require either harsh radical conditions or expensive Ir-based photocatalysis . Treatment of photoproduct 4ap with base smoothly leads to the substrate class of aziridines 18 , representing privileged structural motifs in organic chemistry . We next investigated the tosyl and nosyl deprotection for representative examples (Scheme F).…”

“…18 Treatment of photoproduct 4ap with base smoothly leads to the substrate class of aziridines 18, representing privileged structural motifs in organic chemistry. 19 We next investigated the tosyl and nosyl deprotection for representative examples (Scheme 3F). While morpholine derivative 14 and piperidine 15 can smoothly be tosyldeprotected under mild reductive conditions, the introduced nosyl goup offers the possibility to deprotect more functionalized molecules like Ns-5 under much milder redox-neutral conditions, giving halostachine (20) in good yields.…”

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…1 However, azetidines have found great utility in medicinal chemistry to rigidify alkyl-substituted amines, to explore new chemical space, and as synthetic building blocks (Scheme 1A). 1–4 While azetidines occur infrequently in natural products, Kato et. al.…”

“…Given the strain present in 5 , we propose that ring-opening to give the ( Z )-2-amidoallyl cation zwitterion 6 is governed by A 1,3 strain. Diastereoselective ring-closure from the back face of 6 delivers 3a with the observed stereochemistry.…”

Syntheses of Tetrahydrobenzoazepinoindoles and Dihydrobenzodiazepinoindoles via Ring-Opening Cyclization of Activated Aziridines with 2-(2-Bromophenyl)-1H-indoles

“…To circumvent the shortcomings of the existing methodologies, we sought an expedient access to both of these indoloazepine skeleta with extensive scope for structural and functional diversification. Based on our longstanding interest in S N 2-type ring opening of activated aziridines 15 followed by cyclization strategies with functionalized nucleophiles to construct chiral aza-heterocycles and other targets of contemporary interest, 16 we recognized the prospect of procuring THB- [2,3]azepino [4,5-b]indoles and DHB- [5,6]- [1,4]diazepino [1,7-a]indoles through the ring opening of activated aziridines with 2-(2-bromophenyl)-1H-indoles by exploiting their C3 and N centers as nucleophilic sites, respectively, followed by metal-assisted C−N bond-forming cyclization. Herein, we wish to report our results as a Letter.…”