Mechanistic Study of Nickel-Catalyzed Reductive Coupling of Ynoates and Aldehydes

Abstract

In this work, (1,5-hexadiene)Ni(SIPr) (SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene) is used in place of Ni(COD)/SIPr·HBF/KOBu (COD = 1,5-cyclooctadiene) as a more robust catalyst for regioselective reductive coupling of ynoates and aldehydes with triethylsilane. The catalytic reaction of ethyl 3-(trimethylsilyl)propiolate and methyl 4-formylbenzoate shows first-order dependence on aldehyde and catalyst concentrations, inverse first-order dependence on [ynoate], and no dependence on [silane]. The kinetics data, coupled with deuterium-labeling experiments, support a mechanism involving dissociation of the ynoate from a catalytically dormant nickelacyclopentadiene intermediate prior to turnover-limiting formation of a catalytically active nickeladihydrofuran.

NHC Ligands Tailored for Simultaneous Regio- and Enantiocontrol in Nickel-Catalyzed Reductive Couplings

“…The reaction mediated with bulky ( i -Pr) 3 SiH afforded only trace amounts of the reductive coupling product (Table , entry 4). This is likely due to inefficiencies of the bulky silane to participate in an effective σ–bond metathesis with the metallacycle intermediate. , In addition to 4b , other ligands 4a , 4c , and 4d were also tested, and slightly decreased enantioselectivity was observed for all cases (Table , entries 5–7). Next, the possibility of decreasing the catalyst loading was examined.…”

Entrances, Traps, and Rate-Controlling Factors for Nickel-Catalyzed C–H Functionalization

“…We speculate that trace impurities in the reaction mixture could be deactivating the catalyst. The high sensitivity of the active nickel catalyst at low concentrations has been observed, which is likely why relatively high catalyst loadings are needed for many nickel-catalyzed organic transformations …”

“…We speculate that trace impurities in the reaction mixture could be deactivating the catalyst. The high sensitivity of the active nickel catalyst at low concentrations has been observed, 21 which is likely why relatively high catalyst loadings are needed for many nickel-catalyzed organic transformations. 11 The results from the computational analysis and kinetics experiments corroborate several aspects of the reaction: (1) an alkyne-ligated intermediate, i.e.…”