Classical-Reaction-Driven Stereo- and Regioselective C(sp³)-H Functionalization of Aliphatic Amines

Abstract

A large variety of synthetic methods have been developed for the synthesis of functionalized aliphatic amines because of their broad spectrum of application. Metallic reagents/catalysts and/or toxic oxidants are involved in most of the cases. Direct CH functionalization of aliphatic amines via their classical condensation reactions with suitable carbonyl compounds is advantageous because this method avoids hazardous metallic reagents, toxic oxidants and pre-activation/pre-functionalization step(s). In this account, the concept of direct CH functionalization of aliphatic amines based on the classical condensation-isomerization-addition (CIA) strategy followed by recent contributions from our ongoing research in the field along with relevant examples from other groups are described. Successes in stereo- and regioselective CC and CO bond formation via direct α- as well as β-C(sp(3) )-H functionalization are discussed.

Condensation-Based Methods for the C–H Bond Functionalization of Amines

“…Aspects of this topic were previously covered in the form of Accounts by us in 2015, 5 and by the Jana group in 2016. 6 This Review aims to provide a more comprehensive coverage, including early contributions that have not been reviewed in detail elsewhere, in addition to the many studies that have appeared since the publication of the above mentioned Accounts. The coverage of this Review extends to the end of 2020.…”

Redox-triggered cascade dearomative cyclizations enabled by hexafluoroisopropanol

“…The direct α-C–H functionalization of amines provides the most powerful toolbox for the synthesis of highly functionalized cyclic amines, which are increasingly momentous scaffolds in the exploration of new pharmaceuticals. 1 The desire for an oxidant-free and green process has brought about the renaissance of intramolecular hydride transfer as a key step for α-C–H functionalization of amines. 2 The atom-economic and redox-neutral nature of this transformation makes it ideal for sustainable and complexity-enhancing amine synthesis.…”

Metal Free C–H Functionalization Enabled Diastereoselective Multicomponent Reaction of N-Heterocycles to Fused Heteropolycycles

“…For example, polyheterocyclic skeletons of perinadine A and pyralomicins are built on the functionalized pyrrolidine. Various approaches were developed for the preparation of functionalized aliphatic amines . In contrast to the classical multistep N-cycloalkylation strategy, direct C–H functionalization of saturated amines is of great interest as this strategy allow one to access the desired products in a single step avoiding the additional step(s) for preactivation, prefunctionalization, or removal of the protecting group.…”