Nickel-catalyzed reductive coupling of alkyl halides with other electrophiles: concept and mechanistic considerations

Abstract

The formation of C-C bonds directly from catalytic reductive cross-coupling of two different electrophiles represents one of the practical synthetic protocols that differs from the conventional nucleophile/electrophile coupling methods. Particularly the reductive coupling of alkyl electrophiles with other electrophiles is still a challenge. This account summarizes the advances of the formation of C(sp 3 )-C(sp 3 ) bonds between two alkyl electrophiles, with emphasis on the control of chemoselectivity that is exceedingly challenging to achieve due to similar structures and reactivities of two unactivated alkyl halides. The coupling of alkyl halides with aryl or acyl electrophiles was also discussed based on the chemistry developed by our group, followed by a brief overview for the reactions of tertiary alkyl halides. In the end, a brief outlook of the challenges in this exciting field was illustrated. Whereas the reaction mechanisms generating alkylalkyl products are proposed to involve reactions of Ni(I) species with alkyl halides to generate Ralkyl-Ni(III)-Ralkyl intermediates through a radical/Ni cage-rebound process, evidence seemingly supports that a radical chain mechanism governs the acylation and arylation of alkyl halides. The latter features a cage-escaped alkyl radical.

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].…”

“…A summary of Ni-catalyzed reductive ketone formation has been detailed in recent reviews [1,5]. The coupling protocols are suited for primary and secondary alkyl halides with acid derivatives, including acid chlorides, anhydrides, and in situ activated acids in the presence of Boc 2 O and MgCl 2 [63][64][65][66][67][68].…”

“…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 …”

“…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].…”