Cross-Electrophile Coupling: Principles of Reactivity and Selectivity

Abstract

A critical overview of the catalytic joining of two different electrophiles, cross-electrophile coupling (XEC), is presented with an emphasis on the central challenge of cross-selectivity. Recent synthetic advances and mechanistic studies have shed light on four possible methods for overcoming this challenge: (1) employing an excess of one reagent; (2) electronic differentiation of starting materials; (3) catalyst–substrate steric matching; and (4) radical chain processes. Each method is described using examples from the recent literature.

Nickel-Catalyzed Reductive Couplings

“…The last section of this chapter summarizes the coupling of C(sp 2 )-halides with other C(sp 2 )-and C(sp)-electrophiles. Due to the extensive reviews that have been published on reductive acylation (including CO 2 fixation), arylation of alkyl electrophiles [1][2][3][4][5][6], electrochemical coupling, as well as Co-catalyzed reductive coupling methods [3], only recent progress will be highlighted for these chemistries. [21].…”

“…In recent years, development of transition metal-catalyzed cross-coupling between two electrophiles has received considerable attention (for reviews, see [1][2][3][4][5][6]). These methods avoid the prepreparation of nucleophiles that are often converted from their more stable and accessible electrophile precursors, which may become critically useful when entries to certain nucleophiles are exceedingly difficult [7,8].…”

“…These methods avoid the prepreparation of nucleophiles that are often converted from their more stable and accessible electrophile precursors, which may become critically useful when entries to certain nucleophiles are exceedingly difficult [7,8]. In particular, reductive coupling of alkyl electrophiles with other electrophiles has advanced to be an important strategy for the construction of C-C(sp 3 ) bonds, wherein nickel, and in some cases cobalt, catalysts have proven to be exceptionally powerful (Scheme 1) (for reviews, see [1][2][3][4][5][6]). The electrophiles capable of coupling with alkyl halides and pseudo-halides include C(sp 3 )-(e.g., unactivated alkyl halides and allylic acetates) and C(sp 2 )-substrates (e.g., acyl and aryl/vinyl halides), as well as CO 2 and other carbonyl-type compounds.…”

“…Although insightful understanding of the reaction mechanisms still requires tremendous studies, it is now well accepted that alkyl halides participate in the Nicatalyzed reductive coupling reactions through a radical process [1][2][3][4][5][6]. The radical can diffuse to a bulk solution, and bind to an organonickel [e.g., C(sp 2 …”

Reductive Cross-Coupling of 3-Bromo-2,1-borazaronaphthalenes with Alkyl Iodides

“…Weix et al 7 and Gong et al. 8 have carried out extensive work in the area of reductive cross-couplings in the past decade, illustrating the ability to introduce alkyl halides to aromatic halides under Ni-catalyzed conditions.…”