摘要：Merck Center for Catalysis at PrincetonUniversity, Princeton, New Jersey 08544, United States

转自：康龙化成

Iron-Catalyzed Cross-ElectrophileCoupling for the Formation of All-Carbon Quaternary Centers

Andria L. Pace, Felix Xu, Wei Liu,Marissa N. Lavagnino, andDavid W. C. MacMillan*

Merck Center for Catalysis at PrincetonUniversity, Princeton, New Jersey 08544, United States

—J. Am. Chem. Soc. 2024, 10.1021/jacs.4c14942

Recommended by Chunlei Lu_ MC2

KEYWORDS: Photocatalysis (反应类型),cross-electrophile coupling (反应类型), Fecatalysis (反应类型),C(sp3)− C(sp3) (成键类型),Alkyl bromide (原料),Alkyl sulfonate or alcohol (原料),Quaternary carbon (产物), bimolecularhomolytic substitution (SH2) (其他)

ABSTRACT:Quaternarycarbon centers are desirable targets for drug discovery and complex moleculesynthesis, yet the synthesis of these motifs within traditional cross-couplingparadigms remains a significant challenge due to competing β-hydrideelimination pathways. In contrast, the bimolecular homolytic substitution (SH2) mechanism offers a unique andattractive alternative pathway. Metal porphyrin complexes have emerged asprivileged catalysts owing to their ability to selectively form primarymetal−alkyl complexes, thereby eliminating the challenges associated with tertiaryalkyl complexation with a metal center. Herein, we report an iron-catalyzedcross-electrophile coupling of tertiary bromides and primary alkylelectrophiles for the formation of all-carbon quaternary centers through abiomimetic SH2 mechanism.

SelectiveActivation of Alkyl Halides Toward Cross-coupling via Bimolecular HomolyticSubstitution (SH2)

Insummary, Prof. MacMillan et al have reported a cross-electrophile approach to quaternary center formationvia a biomimeticSH2 bond formation mechanism. Furthermore,they disclose evidence in support of an SN2-typeactivation of primary alkyl electrophiles invoking a highly nucleophilic Fe(I)species. Such a mechanism, while known for stoichiometric reactions, has beencomparably underutilized within the photocatalytic realm. Given the importanceof quaternary carbon centers in bioactive compounds, they anticipate that thisreaction will find broad use across the synthetic community.

来源：新浪财经