Squaramide/Li⁺-Catalyzed Direct S_N1-Type Reaction of Vinyl Triflates with Difluoroenoxysilanes through Vinyl Cations

Abstract

Difluoromethylene-skipped enones have been readily obtained from arylvinyltriflates and aryldifluoroenoxysilanes. While these useful compounds are difficult to synthesize by the classical aldol/dehydration approach, the use of a squaramide/Li + catalyst allows their direct formation via a vinyl carbocation paired with a weakly coordinating perfluorinated alkoxyaluminate. This strategy makes possible a reaction between a typically weak electrophile and a weak nucleophile. Control experiments and DFT computations shed light on the mechanism of this transformation.

α-Vinylation of Ester Equivalents via Main Group Catalysis for the Construction of Quaternary Centers

“…Moreover, given that increased substitution of vinyl sulfonates enables more facile ionization, it was hypothesized that this approach would allow for the generation of fully substituted vinyl carbocations that could directly engage in a nucleophilic attack by enolate equivalents. , Herein we report a main group-catalyzed α-vinylation reaction to construct highly congested quaternary centers fused to tetrasubstituted olefins. During the late-stage preparation of this manuscript, Chen and co-workers disclosed trapping vinyl cations with silyl enol ethers to access difluoromethylene-skipped enones utilizing squareamide additives; however, though complementary to this report, this method does not appear to enable access to the sterically congested motifs of interest to this study …”

“…During the late-stage preparation of this manuscript, Chen and co-workers disclosed trapping vinyl cations with silyl enol ethers to access difluoromethyleneskipped enones utilizing squareamide additives; however, though complementary to this report, this method does not appear to enable access to the sterically congested motifs of interest to this study. 15 With reaction conditions inspired by previous work, 11 initial studies commenced with exploring methyl ester silyl ketene acetal 1 and vinyl tosylate 2, and gratifyingly, the desired product (3) was observed using 10 mol % [Li] + [B(C 6 F 5 ) 4 ] − with 1.5 equiv of LiHMDS in o-DFB solvent with a 45% yield (Table 1, entry 1). We elected to utilize vinyl tosylates as the vinyl cation precursor because they are bench-stable crystalline solids that could tolerate full substitution on the olefin and electron-rich aromatic moieties, thereby expanding the scope of substrates that could be employed.…”

“…During the late-stage preparation of this manuscript, Chen and co-workers disclosed trapping vinyl cations with silyl enol ethers to access difluoromethylene-skipped enones utilizing squareamide additives; however, though complementary to this report, this method does not appear to enable access to the sterically congested motifs of interest to this study. 15 …”