Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles These reactions have proven particularly useful for the coupling of sec-alkyl electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions

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Nickel-Catalyzed Enantioselective Reductive Cross-Coupling Reactions.

The fields of C-H functionalization and photoredox catalysis have garnered enormous interest and utility in the past several decades. Many different scientific disciplines have relied on C-H functionalization and photoredox strategies including natural product synthesis, drug discovery, radiolabeling, bioconjugation, materials, and fine chemical synthesis. In this Review, we highlight the use of photoredox catalysis in C-H functionalization reactions. We separate the review into inorganic/organometallic photoredox catalysts and organic-based photoredox catalytic systems. Further subdivision by reaction class-either sp2 or sp3 C-H functionalization-lends perspective and tactical strategies for use of these methods in synthetic applications.

Photoredox-Catalyzed C-H Functionalization Reactions.

Pyridinium salts are valuable building blocks, which have been widely applied in various organic transformations during the past few decades. In particular, N-functionalized pyridinium salts have b...

Recent Advances in Pyridinium Salts as Radical Reservoirs in Organic Synthesis

In this Review, we highlight recent advances in the understanding and design of N-functionalized pyridinium scaffolds as redox-active, single-electron, functional group transfer reagents. We provide a selection of representative methods that demonstrate reactivity and fundamental advances in this emerging field. The reactivity of these reagents can be divided into two divergent pathways: homolytic fragmentation to liberate the N-bound substituent as the corresponding radical or an alternative heterolytic fragmentation that liberates an N-centered pyridinium radical. A short description of the elementary steps involved in fragmentation induced by single-electron transfer is also critically discussed to guide readers towards fundamental processes thought to occur under these conditions.

Pyridinium Salts as Redox-Active Functional Group Transfer Reagents.

Transition metal catalyzed cross-electrophile coupling of alkyl electrophiles has evolved into a privileged strategy that permits the facile construction of valuable C(sp3)-C bonds. Numerous elegant Ni-catalyzed coupling methods, for example, arylation, allylation, acylation, and vinylation of primary and secondary alkyl halides have been developed. This prior work has provided important mechanistic insights into the selectivity and reactivity of the coupling partners, which are largely dictated by both the catalysts and the reactants. In spite of the advances made to date, a number of challenging issues remain, including (1) achieving stereoselective syntheses of C-C bonds that rely primarily on functionalized or activated alkyl precursors, (2) diversifying the electrophiles, and (3) gaining insights into the underlying reaction mechanisms.In this Account, we summarize a number of Ni- and Fe-catalyzed reductive C-C bond forming methods developed in our laboratory, which have allowed us to couple activated, sterically hindered tertiary alkyl and C(sp3)-O bond electrophiles and to access methylated and trifluoromethylated products, esters, C-glycosides, and quaternary carbon centers. We will begin with a brief discussion of Ni-catalyzed chemoselective construction of unactivated alkyl-alkyl bonds, with focus on the effects of ligands and reductants, along with leaving group-directed reactivities of alkyl halides, and the role they play in promoting the reductive coupling of activated electrophiles, including methyl, trifluoromethyl, and glycosyl electrophiles, and chloroformates. Matching the reactivities of these electrophiles with suitable coupling partners is considered essential for success; this is something that can be tuned by means of appropriate Ni catalysts. Second, we will detail how tuning the steric and electronic effects of nickel catalysts with labile pyridine-type ligands and additives (primarily MgCl2) permits effective creation of arylated all-carbon quaternary centers through the coupling of aryl halides with sterically encumbered tertiary alkyl halides. In contrast, the use of bulkier bipyridine and terpyridine ligands permits the incorporation of relative small-sized acyl and allyl groups into acylated and allylated all-carbon quaternary centers. Finally, we will show how the knowledge gained with halide electrophiles enabled us to develop methods that permit the coupling of tertiary alkyl oxalates with allyl, aryl, and vinyl electrophiles, wherein Barton C-O bond radical fragmentation is mediated by Zn and MgCl2 and promoted by Ni catalysts. The same protocol is applicable to the arylation of secondary alkyl oxalates derived from α-hydroxyl carbonyl substrates, which involves the formation of relatively stable α-carbonyl carbon centered radicals. Thus, this Account not only summarizes synthetic methods that allow formation of valuable C-C bonds using challenging electrophiles but also provides insight into the relationship between the structure and reactivity of the substrates and catalysts, as well as the effects of additives.

Cross-Electrophile Couplings of Activated and Sterically Hindered Halides and Alcohol Derivatives.

Ni-catalyzed Reductive Deaminative Arylation at sp3 Carbon Centers

A dual catalytic sp3 α C–H arylation and alkylation of benzamides with organic halides is described. This protocol exhibits an exquisite site selectivity, chemoselectivity, and enantioselectivity p...

Dual Catalytic Platform for Enabling sp3 α C–H Arylation and Alkylation of Benzamides

A dual catalytic sp3 a C–H arylation & alkylation of benzamides with
organic halides is described. This protocol exhibits excellent chemoselectivity
and exquisite site-selectivity, offering a complementary reactivity mode to
existing sp3 arylation or
alkylation events via either transition metal catalysis or photoredox events

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Hongfei Yin

Papers

Ni-catalyzed Reductive Deaminative Arylation at sp3 Carbon Centers

Dual Catalytic Platform for Enabling sp3 α C–H Arylation and Alkylation of Benzamides

A Dual Catalytic Platform for Enabling sp3 α C–H Arylation & Alkylation of Benzamides