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Metallaphotoredox catalysis (alt. spelling “metallophotoredox”) is a type of dual-catalysis reaction between photoredox catalysis and transition-metal-catalysis. The traditional cross-coupling reactions are effective to deliver C(sp2)–C(sp2) bonds but are challenging for the C(sp3) centers due to the low rate of transmetallation as well as the ease of undergoing unwanted β-hydride elimination in the catalytic cycle.  The idea of metallaphotoredox catalysis is to undergo a “dual-catalysis single-electron transmetallation” approach, in which a high-energy radical is generated by single-electron transfer (SET) in the photoredox catalytic cycle and then captured by the metal center in the transition-metal catalytic cycle. Indeed, this strategy has shown robust synthetic versatility in constructing C(sp2)–C(sp3)/ C(sp3)–C(sp3) and later for C–hetero bonds under mild conditions.

Common Photoredox Catalysts
Some commonly used photoredox catalysts (PC) are Ru- or Ir-based complexes, such as [Ir(dFCF3ppy)2(bpy)]PF6 and Ru(bpy)3](PF6). In 2016, Zhang group developed six cheap, sustainable, and efficient donor−acceptor(D–A) fluorophores as alternative photocatalytic organic dyes, including 4−CzIPN, 2−CzIPN, 4−CzPN, 2−CzPN, 4−CzTPN, and 2−CzTPN.



Transition-Metal Catalysts
Multiple transition metals, including Ni , Pd , Cu  , Mn  , Au  , and Co have been used in metallaphotoredox catalysis. Among those, Ni is the most widely used, because: 1. Ni can adopt both high-spin and low-spin configurations with oxidation states ranging from Ni(0) to Ni(IV). 2. Ni has lower reduction potential, atomic radius, and electronegativity compared to Pd, which can facile desired oxidative addition of Ni(0) to C–O and C–N bonds. 3. Alkylnickel would undergo slower and more predictable β-hydride elimination (β-H) than palladium. .

General Mechanism (use R1 = Ar, R2 = Alkyl and nickel as an example)
Note: The mechanism is still debated and may vary from case to case.



History and Development
In 2011, Sanford and co-works reported a palladium-catalyzed directed C–H arylation with photocatalyst Ru(bpy)3Cl2. The aryl radicals were generated by using aryldiazonium salts, which can be captured by Pd(II) species to generate Pd(III). This paper illustrates the potential of combing transition-metal catalysis and photoredox catalysis.



Carbon–Carbon Bond
Inspired by the work of Sanford, in 2014, Macmillan and Molander lab independently published two Ni/photoredox dual catalytic reactions around the same time. Macmillan lab has used carboxylic acid as the radical precursor, while Molander lab used alkyl trifluoroborates as the radical precursor. Later, other radical sources, such as alkylsilicates, 4-substituted 1,4-dihydropyridines (DHPs) and sulfinate salts were used in later development.



Asymmetric Reaction
In general, most of the enantioselective metallaphotoredox catalytic reactions are achieved by using chiral ligands. Some frequently used chiral ligands are bisoxazoline ligands(BOX), phospinooxazoline ligands(PHOX) , biimidazoline ligands(BiIm) and chiral phosphine ligand s.



In 2016, Macmillan lab future extended the decarboxylative arylation and developed an enantioselective decarboxylative arylation between α-amino acids and aryl halides. Various aryl halides and amino acids are tolerated, giving moderate yields and high ee (82-92% ee).



Carbon–Heteroatom Bond
In 2017, McCusker and Macmillan lab demonstrated a novel C–O bond formation by photosensitized nickel catalysis. The difference between a photosensitized pathway and a SET process is the direct accessible excited Ni(II) species via excitation without any photocatalyst.

Late-Stage Application
Recently, Rovis lab developed a late-stage Ni/photoredox dual catalyzed N-Me selective α-arylation of trialkylamines. Many drug-like benzyl dialkylamines are tested, giving moderate to high yields.

Development from Industry (Flow Reactor)
Scaling up a transition-metal-catalyzed and light dual-catalyzed reaction is challenging. According to the Beer–Lambert law, the light intensity has an exponential decrease with the increasing depth of the reaction medium. Recently, in attempting to improve the yields and productivity from batch reactions to flow reactions, two new flow photoreactors have been designed for MacMillan-type C(sp2)–C(sp3). The segmented flow reactor designed by Jensen lab and Novartis can achieve 0.077 g/h with identical 40 W Kessil A160 WE lamps and space-time yield = 14.5 g L–1 h–1. In 2020, another HANU HX 15 photocatalysis reactor designed by EcoSynth future improve the yields to 0.87 g/h with quasi-monochromatic 405 nm LEDs. In this case, space-time yield = 62.1 g L–1 h–1.