Mechanistic Understanding of Arylation vs Alkylation of Aliphatic C_sp3–H Bonds by Decatungstate–Nickel Catalysis

Abstract

Computational analysis of the arylation of aliphatic Csp3–H bonds catalyzed by decatungstate–nickel validates the reaction mechanism and provides valuable insights into how to accomplish the corresponding alkylation. Our analysis indicates that the light-excited decatungstate photocatalyst activates one of the Csp3–H bonds by a hydrogen atom transfer reaction involving the bridging O atoms of decatungstate. The generated alkyl radical reacts with a bipyridine-based Ni catalytic species to form a NiI-alkyl intermediate. Oxidative addition of aryl bromide to this intermediate leads to a NiIII complex, from which the cross-coupling product is liberated via reductive elimination. We also investigated the corresponding prototype reaction where the aryl bromide is replaced by an alkyl bromide, which suggested a too high energy barrier for the oxidative addition of the alkyl bromide to the NiI-alkyl intermediate. Variation of the steric and electronic properties of the bipyridine ligand suggests that steric encumbrance in the 6,6′ position can promote oxidative addition of the alkyl bromide as verified by ad hoc experimental tests.

The Role of Excited States of LNiII/III(Aryl)(Halide) Complexes in Ni–Halide Bond Homolysis in the Arylation of Csp3–H Bonds

“…The resulting THF• binds to doublet 3-Ni I to give the 4-Ni II intermediate. Consistent with our previous studies, , this is a highly exergonic and barrierless step. The inner-sphere C sp3 –H activation pathway takes place via the concerted transition state T [3–4] ‡ and an activation barrier of 12.0 kcal/mol (red line, Figure ).…”

“…Along the M1 pathway, EnT is involved from T Ir III to 2-Ni II , as proposed by Molander and co-workers (Figure 2). 33 The EnT step results in the excited state 37,38 this is a highly exergonic and barrierless step. The inner-sphere C sp3 −H activation pathway takes place via the concerted transition state T [3−4] ‡ and an activation barrier of 12.0 kcal/mol (red line, Figure 2).…”

“…At odds with these remarkable and broad applications of photoredox-nickel dual catalysis, the amount of computational studies aimed at providing a detailed mechanistic understanding is somehow limited. , Regarding the sequence of oxidation states of nickel within the catalytic cycle, we recently demonstrated that the methodology involving a HAT catalyst follows the sequence Ni I -Ni II -Ni I -Ni III , with the associated radical addition-SET-oxidative addition-reductive elimination (SET = single electron transfer) fundamental elementary steps. , The active catalyst is a LNi I –Br species, and the rate-determining transition state corresponds to oxidative addition of Ar/Alk–Br to the Ni I -complex . The photocatalyst is predicted to activate the nickel complex by SET.…”

Metallaphotoredox catalysis for sp3C–H functionalizations through hydrogen atom transfer (HAT)

“…It has been suggested that final SET between the Ni( i ) species and the doubly reduced decatungstate species ( 110 ) regenerates the active Ni(0) species { E p (Ni II /Ni 0 ) = −1.47 V vs. Ag/Ag + in MeCN, ( E red 1/2 ([W 10 O 32 ] 5− /[W 10 O 32 ] 6− ) = −1.52 V vs. Ag/Ag + in MeCN)}. 99 Building upon this strategy, Kong and co-workers applied it to the three-component difunctionalization of alkenes, demonstrating its utility in the selective late-stage functionalization of complex natural products and the concise synthesis of pharmaceutically relevant molecules (Scheme 19b). 100 In addition, Noël and co-workers reported the C(sp 3 )–H acylation and arylation in a continuous flow, offering significantly reduced reaction times compared to traditional batch reactions (Scheme 19c).…”

Theoretical Underpinning of Synergetic Ir/Cu-Metallaphotoredox Catalysis in Multicomponent C–N Cross-Coupling Reactions

“…However, detailed mechanistic investigations are scarce compared to the available synthetic methodologies. − To improve the mechanistic understanding, computational tools have emerged as powerful methods to elucidate the factors controlling reactivity and selectivity in these complex catalytic transformations. Recently, our group has focused on computational mechanistic investigations on the Ir III –Ni 0/II catalyzed cross-coupling of C sp3 –H bonds. − Those reports aim at identifying the preferred mechanism of the photoredox cycle, Ni-catalytic cycle, and the cooperative nature of the photosensitizer. In comparison with the recent mechanistic studies on PC-Ni dual catalysis, , our understanding of PC-Cu dual catalysis is limited. − Considering the lack of mechanistic understanding and expecting a potential development, we performed a systematic computational study aimed at providing mechanistic insights into a prototype Ir III –Cu II dual catalyzed multicomponent reaction (Scheme a) …”