The formation of C‐heteroatom bonds represents an important type of bond‐forming reaction in organic synthesis and often provides a fast and efficient access to privileged structures found in pharmaceuticals, agrochemical and materials. In contrast to conventional Pd‐ or Cu‐catalyzed C‐heteroatom cross‐couplings under high‐temperature conditions, recent advances in homo‐ and heterogeneous Ni‐catalyzed C‐heteroatom formations under mild conditions are particularly attractive from the standpoint of sustainability and practicability. The generation of NiIII and excited NiII intermediates facilitate the reductive elimination step to achieve mild cross‐couplings. This review provides an overview of the state‐of‐the‐art approaches for mild C‐heteroatom bond formations and highlights the developments in photoredox and nickel dual catalysis involving SET and energy transfer processes; photoexcited nickel catalysis; electro and nickel dual catalysis; heterogeneous photoredox and nickel dual catalysis involving graphitic carbon nitride (mpg‐CN), metal organic frameworks (MOFs) or semiconductor quantum dots (QDs); as well as more conventional zinc and nickel dual catalyzed reactions.

Cascade reactions that produce multiple chemical bonds in one synthetic operation are important in the efficient construction of complex molecules.

Unsaturated carbon-carbon bonds are one of the most common and important structural motifs in many organic molecules, stimulating the continuous development of general, efficient, and practical strategies for their functionalisation. Herein, we report a one-pot difunctionalisation of alkynes via a photoredox/nickel dual catalysed three-component cross coupling reaction under mild conditions, providing access to a series of highly important trisubstituted alkenes. Notably, in contrast to the traditional methods which are based on the steric hindrance of the substrates to control the reaction selectivity, both E-and Z-isomers of trisubstituted alkenes which are often energetically close, can be obtained via choosing an appropriate photocatalyst with a suitable triplet state energy. Beyond the immediate practicality of this transformation, this newly developed methodology might inspire the development of diverse and important one-pot functionalisations of carbon-carbon multiple bonds via photoredox and transition-metal dual catalysed multi-component reactions.Multi-component reactions are a class of useful transformations employed widely for the efficient synthesis of diverse compounds in organic synthesis 1-6 . In the past decades, significant progress has been achieved in the field of difunctionalisation of carbon-carbon multiple bonds via multi-component reactions. However, the employed methods rely largely on the use of organometallic species such as Grignard reagents 7 , organoboron 8 and organolithium 9 reagents and require high temperatures or multistep reactions. More recently, radical-mediated transformations have been developed, providing a good alternative for the one-pot difunctionalisation of these motifs. In this case, a radical is generally generated from a suitable precursor via a single electron transfer process by using O 2 10 , transition metal species 11-14 or photocatalysts [15][16][17] . The generated radical adds to the alkyne or alkene moiety to give a vinyl or alkyl radical intermediate. For transition metal catalysed transformations, various radical precursor including sulfonyl chlorides 11 , activated alkyl bromides 12 , and fluoroalkyl iodides 13 were used in the cross-coupling reactions with organoboron reagents. For

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.

We report here a comprehensive computational analysis of the mechanisms of the photoredox-nickel-HAT (HAT: hydrogen atom transfer) catalyzed arylation and alkylation of αamino Csp3-H bonds developed by MacMillan and coworkers. Different alternatives for the three catalytic cycles were tested to identify unambiguously the operative reaction mechanism. Our analysis indicated that the IrIII photoredox catalyst, upon irradiation with visible light, can be either reduced or oxidized by the HAT and nickel catalysts, respectively, indicating that both reductive and oxidative quenching catalytic cycles can be operative, although the reductive cycle is favored. Our analysis of the HAT cycle indicated that activation of a -amino Csp3-H bond of the substrate is facile and selective relative to activation of a -amino Csp3-H bond. Finally, our analysis of the nickel cycle indicated that both arylation and alkylation of α-amino Csp3-H bonds occurs via the sequence of nickel oxidation states NiI-NiII-NiI-NiIII, and of elementary steps: radical addition-SET-oxidative addition-reductive elimination. transition metal catalysis can be a winning methodology to solve some of the challenges related to functionalization of Csp3-H bonds within C-C cross-coupling schemes.31-34 Recently, a strategy for the functionalization of α-amino Csp3-H bonds using photoredox catalysis, induced by visible-light in combination with a nickel and an organocatalyst, was reported by MacMillan and coworkers (Scheme 1).20, [35][36][37] In this protocol the organocatalyst acts as a hydrogen atom transfer, HAT, agent, generating an alkyl radical by selective activation of a α-amino Csp3-H bond. This merger has culminated in the ability to cross-couple alkyl radicals with metal-activated electrophiles, such as aryl and alkyl bromides, to forge new Csp3-Csp2 and Csp3-Csp3 bonds.Despite a large number of experimental papers in the field of photoredox-nickel dual catalysis, a comprehensive mechanistic picture of this chemistry is still missing. Focusing on theoretical studies, for C-N cross-coupling reaction it has been proposed that a Ni0 species, generated in situ, is the active coupling catalyst and the mechanism involves the modulation of the nickel oxidation state by SET from the photoredox catalyst, rather than by EnT.38 In contrast, for C-O cross-coupling it has been proposed that a NiI species is the active coupling catalyst.39 Different conclusions have been also proposed to explain formation of C-C bonds. In the case of the cross-coupling of aryl bromides with C-centered radicals derived from alkyltrifluoroborates it was proposed that a Ni0 species is the active coupling catalyst, with the Ni0-NiI-NiIII-NiI sequence of oxidation states.24 27, 40 Instead, for difunctionalization of alkynes to tri-substituted alkenes, an experimental and computational study indicated that NiI serves as the active catalyst.41 Scheme 1. Reactions and catalysts investigated in this work. The HAT catalyst Q is used for arylation reaction while Q' is used for alkylation reac...

The reductive cross coupling of pyridinium salts derived from readily available primary alkyl amines with aryl halides has been achieved under mild reaction conditions using a nickel catalyst.

An inexpensive nickel(II) catalyst and a hydrosilane were used for the efficient reductive defunctionalization of aryl and heteroaryl esters through a decarbonylative pathway. This versatile method could be used for the removal of ester and amide functional groups from various organic molecules. Moreover, a scale-up experiment and a synthetic application based on the use of a removable carboxylic acid directing group highlight the usefulness of this reaction.

An efficient nickel-catalyzed decarbonylative amination reaction of aryl and heteroaryl esters has been achieved for the first time. The new amination protocol allows the direct interconversion of esters and amides into the corresponding amines and represents a good alternative to classical rearrangements as well as cross coupling reactions.