Abstract
Reactions that take place via C–H functionalization are valuable tools in organic synthesis because they can be used for the synthesis of target compounds and for the late-stage functionalization of bioactive compounds. Among these, non-directed C(sp3)–H functionalization reactions of saturated nitrogen-containing heterocycles have been developed in recent years. However, most of these lead to functionalization at the α-position relative to the heteroatom, and reactions at the β- or γ-positions are limited since these bonds are stronger and less electron-rich. Hence, in this review, we will discuss non-directed β- or γ-C(sp3)–H functionalization reactions of saturated nitrogen-containing heterocycles, which are of recent interest to medicinal chemists. These methods are attractive in order to avoid the pre-functionalization of substrates, and to reduce the number of synthetic steps and the formation of byproducts. Such non-directed β- and γ-C(sp3)–H functionalization reactions can be divided into enamine-intermediate-mediated processes and other reaction types described in this review.
1 Introduction
2 Non-Directed β-C(sp3)–H Functionalization of Saturated Nitrogen-Containing Heterocycles via an Enamine Intermediate
2.1 Non-Directed β-C(sp3)–H Functionalization of Saturated Nitrogen-Containing Heterocycles under Acidic, Basic or Thermal Conditions
2.2 Non-Directed β-C(sp3)–H Functionalization of Saturated Nitrogen-Containing Heterocycles under Oxidative Conditions
2.3 Non-Directed β-C(sp3)–H Functionalization of Saturated Nitrogen-Containing Heterocycles under Redox-Neutral Conditions
3 Strategies for Non-Directed β- or γ-C(sp3)–H Functionalization of Saturated Heterocycles Excluding Examples Proceeding via an Enamine Intermediate
4 Summary
Key words
directing-group-free - C(sp
3)–H functionalization - nitrogen-containing heterocycles - enamine intermediate - borrowing hydrogen - late-stage functionalization
