Direct C(sp3)–H Activation of Carboxylic Acids

Abstract

Carboxylic acids are important in a variety of research fields and applications. As a result, substantial efforts have been directed towards the C–H functionalization of such compounds. While the use of the carboxylic acid moiety as a native directing group for C(sp2)–H functionalization reactions is well established, as yet there is no general solution for the C(sp3)–H activation of aliphatic carboxylic acids and most endeavors have instead relied on the introduction of stronger directing groups. Recently however, novel ligands, tools, and strategies have emerged, which enable the use of free aliphatic carboxylic acids in C–H-activation-based transformations.1 Introduction2 Challenges in the C(sp3)–H Bond Activation of Carboxylic Acids3 The Lactonization of Aliphatic Carboxylic Acids4 The Directing Group Approach5 The Direct C–H Arylation of Aliphatic Carboxylic Acids6 The Direct C–H Olefination of Aliphatic Carboxylic Acids7 The Direct C–H Acetoxylation of Aliphatic Carboxylic Acids8 Summary

Direct β‐ and γ‐C(sp3)−H Alkynylation of Free Carboxylic Acids**

“…To further broaden the applicability of our method, we proceeded to study the use of notoriously challenging α‐non‐quaternary acid substrates. Notably, due to the absence of an accelerating Thrope–Ingold effect and additional possible side reactions, such substrates are either not included or have proved particularly challenging in the majority of studies on the direct C−H activation/functionalization of aliphatic carboxylic acids [4a,b] …”

Direkte β‐ und γ‐C(sp3)‐H Alkinylierung freier Carbonsäuren**

“…Um die Anwendbarkeit unserer Methode weiter auszudehnen, untersuchten wir die Verwendung von notorisch herausfordernden α‐nicht‐quartäre Carbonsäuren. Insbesondere aufgrund des Fehlens eines beschleunigenden Thrope‐Ingold‐Effekts und zusätzlicher möglicher Nebenreaktionen sind solche Substrate in der Mehrzahl der Studien zur direkten C‐H‐Aktivierung/Funktionalisierung aliphatischer Carbonsäuren entweder nicht enthalten oder haben sich als besonders herausfordernd erwiesen [4a,b] …”

The Emergence of Palladium‐Catalyzed C(sp3)−H Functionalization of Free Carboxylic Acids

“…The Pd‐complexes′ robust nature might be due to its high electrophilic nature and facile electropalladation of C−H bonds with palladium [2b] . To be mentioned, van Gemmeren's short review on direct C(sp 3 )−H activation of carboxylic acids provided a brief overview of different C−H functionalizations [14] . Few examples for C(sp 3 )−H lactonization [15] and hydroxylation [16] of carboxylic acids were reported under platinum catalysis.…”