Transition‐Metal‐Free Methods for the Remote C−H Bond Functionalization of Cyclic Amines

Abstract

CÀ H bond functionalization is one of the most efficient strategies for the rapid synthesis of cyclic amines containing substituents in the ring, which are core structures of many bioactive molecules. However, it is much more challenging to perform this strategy on remote CÀ H bonds than on α-CÀ H bonds of cyclic amines. This review provides a comprehensive overview on the transition metal-free methods for the remote CÀ H bond functionalization of cyclic amines, complementary to methods relying on transition metal catalysis. Selected substrate scope and discussion of reaction mechanism are given when necessary.

Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions

“…The higher energy lone pair on nitrogen could also alter the absorption characteristics of the substrates or related photophysical processes. The electron richness of these substrates would also enable us to leverage emerging chemistries to install the photoreactive aroyl handle on a wide range of compounds, broadening synthetic utility. − Within the framework of skeletal editing, the ability to install the requisite photoreactive handle on any desired N –Ar heterocycle would prevent the need for a lengthy, inefficient synthesis of targeted substrates from prefunctionalized precursors. From a practical standpoint, these precursor N –aryl compounds are readily accessible through precedented C–N cross-coupling methods (Buchwald–Hartwig, Ullman, etc.)…”

Visible-light-induced dehydrogenative β-trifluoromethylthiolation of tertiary amines and direct β-trifluoromethylthiolation of enamides

“…1 Therefore, the development of environmentally friendly and sustainable approaches for the direct and site-selective C(sp 3 )–H functionalization of saturated heterocycles is of great significance, especially for drug discovery. 2…”

Annulation of O-silyl N,O-ketene acetals with alkynes for the synthesis of dihydropyridinones and its application in concise total synthesis of phenanthroindolizidine alkaloids

“…The construction of N -heterocycles containing multiple substituents still remains an important synthetic challenge ( Vo et al, 2014 ; Nandakumar et al, 2015 ; He et al, 2021 ; Chen et al, 2023 ). We recently described the Ag(I) and Brønsted acid co-catalyzed cyclization of an enamine with a tethered alkyne moiety as a one-pot method for pyridinium formation ( Scheme 1A ) ( Lee et al, 2023 ).…”