Rh-Catalyzed Synthesis of Isobenzofurans via Donor/Donor-Type Metal Carbenoids and Their [4 + 2] Cycloaddition.
Morita, N.; Yoshikawa, S.; Ota, E.; Yamaguchi, J.
J. Org. Chem. 2025, 90, 5986–5999.
DOI 10.1021/acs.joc.5c00339
A rhodium-catalyzed synthesis of isobenzofurans via donor- and donor-type metal carbenoids has been developed. Nosylhydrazones were used as carbene precursors, generating rhodium carbenoid species under basic conditions. These intermediates underwent intramolecular cyclization with ester groups to afford isobenzofurans, which subsequently participated in a highly endo-selective [4 + 2] cycloaddition with maleimides and other dienophiles. The reaction exhibited a broad substrate scope, accommodating various ester and aryl substituents while maintaining excellent regio- and stereoselectivity. Mechanistic studies, including control experiments, NMR analysis, and computational calculations, revealed that the reaction proceeds through a rhodium carbenoid intermediate, leading to the formation of isobenzofuran prior to cycloaddition. The endo-selectivity was found to originate from the difference in activation energies between the transition states, as supported by computational studies. Additionally, the isolation of the diazo intermediate and its direct conversion to isobenzofuran confirmed the stepwise nature of the transformation. This study expands the utility of donor- and donor-type carbenoids in organic synthesis, demonstrating their effectiveness in constructing highly reactive isobenzofurans under mild conditions.