摘要：KEYWORDS:Crosselectrophile coupling (XEC) (反应类型),phosphonium salt (原料),alkyl halide (原料), C(sp3)–C(sp3) (成键类型), LiHMDS(试剂), C(sp3)

转自：康龙化成

Coupling of Unactivated Alkyl Electrophiles Using Frustrated Ion Pairs

Sven Roediger, Emilien Le Saux,Philip Boehm & Bill Morandi

Laboratorium fur Organische Chemie,ETH Zurich, Zurich, Switzerland

—Nature 2024,DOI: 10.1038/s41586-024-08195-1

KEYWORDS: Crosselectrophile coupling (XEC) (反应类型),phosphonium salt (原料),alkyl halide (原料), C(sp3)–C(sp3) (成键类型), LiHMDS(试剂), C(sp3)–P (断键类型), C(sp3)–X (断键类型),frustrated ion pair (其他)

ABSTRACT: Cross-electrophilecoupling reactions have evolved into a major strategy for rapidly assemblingimportant organic molecules. Two readily accessible electrophiles are coupledto form new C–C bonds, providing a key advantage over traditional crosscoupling strategies that require the preformation of reactive organometallic species.Yet, the formation of C(sp3)–C(sp3) bonds that form the core of nearly allorganic compounds remains highly challenging with current approaches, callingfor the design of innovative new strategies. Here we report a distinct,transition-metal-free platform to form such bonds without the need foractivating or stabilizing groups on the coupling partners. The reaction isenabled by an unusual single-electron transfer in a frustrated ion pair, and itcan couple fragments containing functional groups that would be challenging inrelated transition-metal-catalysed processes. Moreover, we could further leverage this new mechanistic manifold inthe design of other reactions, showing the broad potential of this type ofreactivity. We anticipate that our results will provide a framework for furtherexploration of this reactivity pattern to tackle challenging problems inorganic synthesis.

Backgroundand This Work:

a, Limitations of transition-metal-catalysed C(sp3)–C(sp3) XECs. b, Current methods fortransition-metal-free C(sp3)–C(sp3) XECs. c, Discovery of C(sp3)–P bond activation in phosphoniumsalts. d, This work: transition-metal-free C(sp3)–C(sp3) coupling of unactivated substrates enabled by a frustrated ion pair.

Proposed Mechanism

Prof. Bill Morandi andhis co-workers have described the discovery and investigation of anunprecedented coupling related to XEC in which two completely unactivated andnon-organometallic C(sp3) fragments are combined in atransition-metal-free protocol. Alkylphosphonium salts arereacted with alkyl halides inthe presence of a sterically hindered base as the sole reagent to give rise tothe coupled products. Mechanistic studies suggest that the reaction is enabledby an unusual single-electron transfer (SET) in a frustrated ion pair that isreminiscent of frustrated Lewis pairradical reactivity.

来源：新浪财经