Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

•A Ni-catalyzed regime for reductive alkylalkynylation of alkynes is described•Readily accessible N-(acyloxy)phthalimides are used as alkyl group donors•Stereodefined 1,3-enynes bearing diverse functional groups can be generated•The method amenable to cascade annulation transformations Despite key advances in multicomponent dicarbofunctionalization, additions remain limited, and examples involving sp-hybridized electrophiles have not been reported. An inherent challenge the high propensity alkynyl halide undergo undesired homocoupling side reactions, consequently suppressing product formation. As demonstrated here, a that selectively merges with readily available electrophilic bromides developed. This protocol enables access valuable structurally sophisticated stereodefined 1,3-enynes, which further derivatization other useful building blocks. The mechanistic insights derived from synergistic combination redox-active ester an organohalide expected provide practical solutions addressing longstanding problems catalytic systems employ multiple electrophiles. development reaction by orthogonal activation substrates streamlined di-functionalization compelling objective organic chemistry. Alkyne carboalkynylation, particular, offers direct entry different substitution patterns. Here, we show synthesis featuring trisubstituted olefin achieved merging alkynes, bromides, through nickel-catalyzed alkylalkynylation. Products generated up 89% yield single regio- E isomers. Transformations tolerant resulting elaboration synthetically With olefin-tethered N-(acyloxy)phthalimides, radical addition/cyclization/alkynylation process implemented obtain 1,5-enynes. study underscores crucial role esters superior donors compared haloalkanes alkyne dicarbofunctionalizations. 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Switching agent Zn tetrakis(dimethylamino)ethylene (TDAE) led poor yields excessive by-product entries 2 3). Other less effective promoting 4), while electron-rich bipyridine phenanthroline ligands L2?L8 afforded unsatisfactory 5). Changing polar solvents also did improve results 6).Table 1Evaluation conditionsEntryDeviation standard conditionsConversion (%)aReactions performed 0.1 mmol scale. Conversions (based consumption 1a) determined analysis. Value parentheses denotes isolated yield.Yield yield.1none78672Zn instead Mn>95163TDAE Mn36<54Ni(cod)2, NiCl2·glyme NiI2 NiBr2·glyme74–8139–575L2-L8 L131–82<5–556MeCN, DMF DMSO DMA25–82<5–417TMSCl (0.5 added77258ZnCl2 added50159MgBr2 added683610LiBr added8576 (73)Abbreviations: DMA, N,N-dimethylacetamide; DMF, N,N-dimethylformamide; DMSO, dimethyl sulfoxide; cod, 1,5-cyclooctadiene; TDAE, tetrakis(dimethylamino)ethylene; TMSCl, trimethylsilyl chloride; RT, temperature.a Reactions yield. Open table new tab Abbreviations: temperature. order enhance efficiency suppress forma