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
