Rh(DPEPhos)-Catalyzed Alkyne Hydroacylation Using β-Carbonyl-Substituted Aldehydes: Mechanistic Insight Leads to Low Catalyst Loadings that Enables Selective Catalysis on Gram-Scale

Journal of the American Chemical Society
James Barwick-SilkAndrew S Weller

Abstract

The detailed mechanism of the hydroacylation of β-amido-aldehyde, 2,2-dimethyl-3-morpholino-3-oxopropanal, with 1-octyne using [Rh( cis-κ2-P,P-DPEPhos)(acetone)2][BArF4]-based catalysts, is described [ArF = (CF3)2C6H3]. A rich mechanistic landscape of competing and interconnected hydroacylation and cyclotrimerization processes is revealed. An acyl-hydride complex, arising from oxidative addition of aldehyde, is the persistent resting state during hydroacylation, and quaternary substitution at the β-amido-aldehyde strongly disfavors decarbonylation. Initial rate, KIE, and labeling studies suggest that the migratory insertion is turnover-limiting as well as selectivity determining for linear/branched products. When the concentration of free aldehyde approaches zero at the later stages of catalysis alkyne cyclotrimerization becomes competitive, to form trisubstituted hexylarenes. At this point, the remaining acyl-hydride turns over in hydroacylation and the free alkyne is now effectively in excess, and the resting state moves to a metallacyclopentadiene and eventually to a dormant α-pyran-bound catalyst complex. Cyclotrimerization thus only becomes competitive when there is no aldehyde present in solution, and as aldehyde binds so...Continue Reading

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Citations

Apr 16, 2020·Chemistry, an Asian Journal·Tomohiko ShiraiYasunori Yamamoto
Sep 13, 2018·Chemistry : a European Journal·Ana M GeerCristina Tejel
May 27, 2021·The Journal of Organic Chemistry·Muniyappa Vijaykumar, Benudhar Punji

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