Transition metal-catalyzed ketone-directed or mediated C–H functionalization

Abstract

Transition metal-catalyzed C-H functionalization has evolved into a prominent and indispensable tool in organic synthesis. While nitrogen, phosphorus and sulfur-based functional groups (FGs) are widely employed as effective directing groups (DGs) to control the site-selectivity of C-H activation, the use of common FGs (e.g. ketone, alcohol and amine) as DGs has been continuously pursued. Ketones are an especially attractive choice of DGs and substrates due to their prevalence in various molecules and versatile reactivity as synthetic intermediates. Over the last two decades, transition metal-catalyzed C-H functionalization that is directed or mediated by ketones has experienced vigorous growth. This review summarizes these advancements into three major categories: use of ketone carbonyls as DGs, direct β-functionalization, and α-alkylation/alkenylation with unactivated olefins and alkynes. Each of these subsections is discussed from the perspective of strategic design and reaction discovery.

Direct Asymmetric Alkylation of Ketones: Still Unconquered

“…It should be noted that modifications at the α-position of ketones such as arylation, [8] alkenylation and alkynylation, [9] or alkylating methods that involve a previously modified (e.g. halogenated) α-position [10] will not be discussed here.…”

Direkte asymmetrische Alkylierung von Ketonen: noch immer ein unerreichtes Ziel

“…[7] Es sollte angemerkt werden, dass Modifizierungen der a-Position von Ketonen wie Arylierung, [8] Alkenylierung und Alkinylierung [9] ebenso wie Alkylierungsmethoden, an denen eine zuvor veränderte (z. Unerwünschte Reaktionen wie homolytische Kupplungen und die Weiteralkylierung sind ebenfalls allgegenwärtige Probleme.Zudem kann eine nicht gewünschte b-o der g-Alkylierung stattfinden.…”

Rhodium‐Catalyzed Annelation of Benzoic Acids with α,β‐Unsaturated Ketones with Cleavage of C−H, CO−OH, and C−C Bonds

“…[1] Initially, this approach was often limited by the use of complex directing groups, [2] which needed to be installed and later removed, thus adding steps to the overall process.Instate-ofthe-art methods,t he selectivity can be enforced even by ubiquitous functionalities,i ncluding ketone, [3] hydroxy, [4] or carboxylate groups. [1] Initially, this approach was often limited by the use of complex directing groups, [2] which needed to be installed and later removed, thus adding steps to the overall process.Instate-ofthe-art methods,t he selectivity can be enforced even by ubiquitous functionalities,i ncluding ketone, [3] hydroxy, [4] or carboxylate groups.…”