Recent Advances in Base‐Metal‐Catalyzed Carbonylation of Unactivated Alkyl Electrophiles^†

Abstract

Comprehensive SummaryTransition metal‐catalyzed carbonylation reactions represent a direct and atom‐economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock. While carbonylation of C(sp2)‐hybridized electrophiles (e.g. aryl halides) is well developed, carbonylation of less reactive unactivated alkyl electrophiles remains challenging. Recently, the use of earth‐abundant base metals including Cu, Co, Mn, Fe, Ni as catalysts has enabled advances in carbonylative coupling of alkyl electrophiles for approaching diverse carbonyl compounds or their derivatives, notably, some of which are of synthetic importance but difficult to be synthesized through previous reported methods. Herein, we have summarized and discussed these recent achievements in base‐metal‐catalyzed carbonylative C–C, C–N, C–O, C–X coupling and other carbonylation reactions of unactivated alkyl electrophiles using CO as C1 source.This article is protected by copyright. All rights reserved.

Nickel-catalyzed acylation of vinylpyridine with alkylzincs under 1 atm CO

“…Until recently, our group has pioneered the development of transition metal-catalyzed acylmetallation reactions using a carbonylation strategy to achieve acylzincation of oxabicycloalkenes, alkynylamides, allenes and styrenes, filling the gap in carbometallation reactions regarding acyl functional groups as nucleophilic fragments (Scheme 1b) 12 Recently, the ligand-accelerated nickel-catalyzed carbonylative transformation with the use of CO gas as the C-1 source has emerged as an alternative means for modern carbonylation by overcoming the formation of the inactive Ni(CO) 4 species. 13,14…”

Nickel-Catalyzed Carbonylative Negishi Cross-Coupling of Unactivated Secondary Alkyl Electrophiles with 1 atm CO Gas

“…This is primarily attributed to the sluggish oxidative addition of sp 3 -hybridized C–X to the low-valent palladium intermediate in the presence of the π-acidic CO. Despite the significant advancements in earth-abundant transition metal-catalyzed alkyl–alkyl cross-coupling over the past two decades, the analogous three-component carbonylative cross-coupling of unactivated alkyl halides, carbon-based organometallic nucleophile with CO gas under mild conditions to construct ketone remains an elusive goal (Scheme b). − …”

Photoredox-catalyzed carbonylative acylation of styrenes with Hantzsch esters

“…6 In recent years, transition metal-catalyzed carbonylation has become one of the most effective methods for constructing carbonyl functional groups. 7 Compared to the synthesis of amides and esters, the carbonylation method for synthesizing ketones is mainly limited to the well-established aryl ketones, benzylic ketones and alkynyl ketones. 8 In addition, these carbonylation strategies still rely on using stoichiometric amounts of main group organometallic reagents and activated organic halides (Scheme 1b).…”