Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles

Abstract

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters and benzylic chlorides are reported. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp 3 ) activation changes from a Nimediated process when benzyl chlorides and Mn 0 are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a Ni II −alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.

Electronic Structures of Nickel(II)-Bis(indanyloxazoline)-dihalide Catalysts: Understanding Ligand Field Contributions That Promote C(sp2)–C(sp3) Cross-Coupling

“…The VT UV–vis–NIR and spectroelectrochemistry studies, when compared with experimental conditions often utilized for nickel-catalyzed reductive cross-coupling (i.e., low temperatures, use of coordinating solvents, relatively mild reducing agents, etc. ), ,, are consistent with the mechanistic investigation of this reaction by Turro and co-workers, which suggests this reaction proceeds via a Ni I/III redox cycle (Scheme ), similar to that proposed by Diao and co-workers for the related cross-coupling of aryl halides . Additional aspects of the optimized reaction conditions can be commented on, however, as derived from the findings in the present study.…”

“…Given the ability to accurately calculate and reproduce experimental formal potentials, the same approach can be used to investigate the bonding and redox properties of the Ni II (IB)­(Vn)­Br (Vn = 1-methyl-4-vinylbenzene; Figure ) resting state, which we were unable to isolate and study electrochemically due to instability . The calculated reduction potential of this species coupled with halide loss is −1.82 V vs Fc +/0 in DMA.…”

“…The “R–Ar” cross-coupled product can then form via reductive elimination. The analogous reactivity considerations for IB complexes and vinyl halides are given in Figure …”

“…Additionally, there is a direct correlation between calculated oxidation potential gaps (Δ E ox between the benzyl-C­(sp 3 ) radical and Ni II (IB)­(Vn)­Br species) and reaction yields obtained from coupling the benzylic radicals generated from the NHP esters (NHP = N -hydroxyphthalimide), with the highest yields observed for reactions between benzyl-C­(sp 3 ) radicals and Ni II (IB)­(Vn)­Br species with calculated oxidation potential gaps (Δ E ox ) of ∼−0.4 V (Figure C). Although care must be taken drawing mechanistic conclusions from reaction yields, given that (1) Ni II (IB)­(Vn)­X is the catalyst resting state (vide infra) and (2) Ni is not involved in generating the radical from the NHP ester, the correlation between reaction yield and Δ E ox reflects the favorability of the radical addition to Ni II (IB)­(Vn)­Br .…”

“…It is also possible for DMA coordination to influence reaction barriers. More detailed mechanistic aspects and reaction kinetics are discussed in ref by Turro et al More broadly, the results described herein suggest future computational studies should also consider explicit solvent coordination in calculated reaction mechanisms.…”