C−H Functionalization of Aldehydes and Ketones with Transient Directing Groups: Recent Developments

Abstract

In order to directly functionalize C−H bonds of complex molecules and, in particular, to control the regioselectivity of the reaction, a wide range of directing groups has been used. However, these directing groups need to be installed and removed for further applications, which may limit the use of C−H activation in synthesis. Concerning aldehydes and ketones, a transient directing group strategy has recently emerged to overcome this drawback. The addition of an additive, in general an amine, allowed the in situ formation of the real directing group to achieve C−H activation. This review presents the latest developments in the field over the period 2020–2023.

Palladium(II)-Catalyzed Tandem γ-C(sp2)–H Arylation and Cyclization for the Construction of Natural Product-Like Polycyclic Fused ortho-Quinone Scaffolds

“…However, it is difficult to avoid the formation of aromatization products in the construction of the hexatomic ring compounds, even when the γ-C(sp 2 )−H activation was involved in the reaction. 12 We hypothesized that a similar strategy could be applied to the synthesis of highly substituted PQs, if the generation of aromatization products can be effectively prevented. Here, we report an efficient approach using a palladium(II)-catalyzed tandem γ-C(sp 2 )−H arylation and cyclization to direct form ortho-quinones (Scheme 1d).…”

“…The C­(sp 2 )–H functionalization of aromatic aldehydes and ketones via transient directing groups ( TDGs ) has been extensively investigated and can be recognized as an efficient strategy for the synthesis of polyfunctionalized aromatic building blocks bearing an aldehyde or ketone functionality. However, it is difficult to avoid the formation of aromatization products in the construction of the hexatomic ring compounds, even when the γ-C­(sp 2 )–H activation was involved in the reaction . We hypothesized that a similar strategy could be applied to the synthesis of highly substituted PQs , if the generation of aromatization products can be effectively prevented.…”