Nickel-Catalyzed Domino Cross-Electrophile Coupling Dicarbofunctionalization Reaction To Afford Vinylcyclopropanes

Abstract

We have established a nickel-catalyzed domino reaction that harnesses sulfonamide, alkyl chloride, and alkyne functionalities in a multistep sequence to afford vinylcyclopropanes bearing tetrasubstituted olefins. The starting materials are prepared by iron-promoted aza-Prins reactions of ynals. This method provides rapid synthetic access to valuable building blocks with applications in medicinal chemistry. Experimental and computational results support the initiation of the catalytic cycle by oxidative addition of the propargylic sulfonamide, and a key ambiphilic allenylnickel intermediate leads to a bifurcated reaction pathway that generates olefin isomers.

Recent DFT Calculations on the Mechanism of Transition‐Metal‐Catalyzed C−O Activation of Alcohols

“…Therefore, we suggest that the Grimme empirical D3 dispersion corrections (Becke‐Johnson‐damping or zero‐damping) [90,91] to be added when using functionals with poorly described noncovalent interactions such as B3LYP. For single‐point calculations, the Minnesota functionals such as M06 have become popular, and have been extensively used in transition metal catalyst systems (not limited to the current review paper) [92–97] . The PBE0 functional also performs well in describing metal‐catalysed systems, and is reliable in both geometry optimization and single‐point energy calculations while balancing computational accuracy and elapsed time.…”

“…For single-point calculations, the Minnesota functionals such as M06 have become popular, and have been extensively used in transition metal catalyst systems (not limited to the current review paper). [92][93][94][95][96][97] The PBE0 functional also performs well in describing metalcatalysed systems, and is reliable in both geometry optimization and single-point energy calculations while balancing computational accuracy and elapsed time. In addition, the double hybridization functionals such as ωB97X-V or ωB97M-V can bring higher accuracy when computational resources allow.…”

Chiral polycyclic benzosultams from photocatalytic diastereo- and enantioselective benzylic C–H functionalization

“…This photochemical reaction can be catalyzed by chiral complexes of cobalt, copper and zinc, suggesting that the nickel catalyst functions as a chiral Lewis acid rather than as a catalyst to enable oxidative addition/reductive elimination sequences. Regarding the stereoselectivity, we posit that the high level of stereodiscrimination when installing two vicinal stereogenic centers in this photochemical reaction might be attributed to the steric effects of the chiral nickel catalyst, the metal cation-chlorine interaction, 46 and potential π-π stacking between the two reactants. 47 Similar effects of terminal substi-tuents in substrates on diastereo-and enantioselectivity have been observed in other intramolecular cyclization reactions.…”

Stereospecific Nickel-Catalyzed Cross-Electrophile Coupling Reaction of Alkyl Mesylates and Allylic Difluorides to Access Enantioenriched Vinyl Fluoride-Substituted Cyclopropanes

“…Next, we considered Pathway 2, where an alkene-bound Ni(0)L 2 displaces the mesylate through a stereoinvertive oxidative addition in an S N 2 fashion to generate the cationic Ni(II) complex B + . 24 The pathway proceeds through the intramolecular MI of intermediate B + to form the cationic α-cyclopropyl Ni(II) intermediate C + . Subsequent BFE and catalyst dissociation deliver product D with overall inversion at the mesylate center, which is consistent with the stereochemical outcome of this reaction.…”

“…Next, we considered Pathway 2, where an alkene-bound Ni(0)­L 2 displaces the mesylate through a stereoinvertive oxidative addition in an S N 2 fashion to generate the cationic Ni­(II) complex B + . The pathway proceeds through the intramolecular MI of intermediate B + to form the cationic α-cyclopropyl Ni­(II) intermediate C + .…”