Mechanistic Origin of Chemo- and Regioselectivity of Nickel-Catalyzed [3 + 2 + 2] Cyclization Reaction

Abstract

A density functional theory (DFT) study was performed to elucidate the mechanism of the Ni-catalyzed [3 + 2 + 2] cyclization reaction of cyclopropylideneacetate with two alkynes. A systematic search showed that the nature of the alkynes determines the choice between two reaction pathways and hence the regioselectivity. Strongly electron-deficient acetylenes preferentially afford 2,5-disubstituted products via nickelacyclopentadienes generated by [2 + 2] cocyclization, whereas normal alkynes afford 3,4- or 3,5-products via an unprecedented pathway involving a [3 + 2] nickelacycle intermediate.

Computational Studies of Synthetically Relevant Homogeneous Organometallic Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT Methods and Mechanistic Insights

“…328−332 For example, Morokuma, Uchiyama and coworkers performed a computational study (at the M06/6-31+G(d)(LANL2DZ) level of theory) on the Ni-catalyzed [3 + 2 + 2] cycloaddition of cyclopropylideneacetate and two alkynes to determine how the nature of the reagents affects the outcome of the reaction (Scheme 23). 333 Two different pathways were suggested to be likely and leading to different isomers of cycloheptadiene, depending not only the bulkiness of the alkyne substituents but also on their electronic nature. Moreover, in their study, all possible transition states were located using the AFIR (artificial force induced reaction) methodology, which can be used to systematically search for transition states of multicomponent reactions.…”

Nickel‐Catalyzed Chemo‐, Regio‐ and Diastereoselective Bond Formation through Proximal CC Cleavage of Benzocyclobutenones

“…[30,31] As ubsequent b-carbon elimination event from either III or in situ generated seven-membered metallacycle [32,33] might lead to the formation of putative p-allyl Ni II metallacycle (IV)t hat ultimately undergoes reductive elimination to form the corresponding benzofused eight-membered ring. [30,31] As ubsequent b-carbon elimination event from either III or in situ generated seven-membered metallacycle [32,33] might lead to the formation of putative p-allyl Ni II metallacycle (IV)t hat ultimately undergoes reductive elimination to form the corresponding benzofused eight-membered ring.…”

Transition‐Metal‐Catalyzed [3+2+2] Cycloaddition Reactions

“…Komagawa and co‐workers have performed DFT calculations to explore the mechanism for the nickel‐catalyzed [3+2+2] cyclization reactions of cyclopropylideneacetate (CPA) with different types of alkynes . The theoretical calculations conclude that the cyclization reaction takes place through two possible pathways ( A and B ), which path is taken depends upon the nature of the alkyne used in these cycloadditions.…”