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The enantioseletive rhodium catalyzed [2+2+2] cycloaddition of alkenyl isocyanates with diaryl acetylenes and 1,2-disubstituted alkenyl isocyanates




Oinen, Mark Emil, author
Rovis, Tomislav, 1968-, advisor
Kipper, Matthew J., committee member
Williams, Robert Michael, committee member
Fisher, Ellen R., committee member

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Elaborating upon the recent discovery of a [2+2+2] rhodium-catalyzed cycloaddition of alkenyl isocyanates with various alkynes, the scope of this rhodiumcatalyzed cycloaddition with diaryl acetylenes was explored. The reaction with pentenyl isocyanate and diaryl acetylenes utilizing [Rh(C2H4)Cl]2 and 3,3'-substituted BINOL phosphoramidites as a catalyst predominantly affords vinylogous amide type products. Investigation into product selectivity reveals that both electronic and steric factors of the ligand have an influence on the product selectivity. Information gleaned from these studies allowed for a change in product selectivity for formation of lactam products with diaryl acetylenes. Selectivity for lactam product is at best 1:1.5 with BINOL phosphites. Vinylogous amide products are formed selectively (>20:1) in the cycloaddition using a variety of BINOL based phosphoramidites. Using 3,3' substituted BINOL based phosphoramidites promising enantioselectivies are obtained in the cycloaddition of diaryl acetylenes and pentenyl isocyanate. In the course of this investigation an interesting effect of substrate on the enantioselectivity was noticed. The ee of the reaction is highly dependent upon the nature of the diaryl acetylene. It was revealed that substrate affects the enantioselectivity by playing the role of spectator ligand in the reaction. Elucidation of the mechanism of the role of this spectator ligand was done by characterization of intermediates, kinetic analysis of the reaction rate and competition experiments between substrates. This effect of spectator ligands was exploited in a synthetically viable way to yield products with high and consistent enantioselectivities. By employing methyl nicotinate, a non-participating spectator ligand, as a stoichiometric additive synthetically useful enantioselectivities can be achieved. Finally, limitations existed within the scope of both alkynes and alkenyl isocyanates on the scope of the rhodium catalyzed [2+2+2] cycloaddition. Acetylene dicarboxylates, and 1,2-disubstituted alkenyl isocyanates were reaction partners that failed to provide cycloadducts under current reaction conditions. In both cases, the resultant cycloadduct would be interesting as they could provide additional synthetic handles for further manipulation of cycloadducts. Identification of undesired byproducts in these reactions allowed for the development of reaction conditions to reduce their formation of these by-products. The reduction in the formation of benzenoids formed from alkyne trimerization allowed for the production of mixtures of lactam and vinylogous amide products using acetylene dicarboxylates. With 1,2-disubstituted alkenyl isocyanates the implementation of reaction conditions which lead to the suppression of 2- pyridone lead to successful formation of the lactam products.


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BINOL phosphoramidites
Ring formation (Chemistry)
alkenyl isocyanates
diaryl acetylenes
Rhodium catalysts
lactam products


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