Valence-isomer selective cycloaddition reaction to synthesize functionalized carbocycles

Abstract The rapid and precise creation of complex molecules while controlling multiple selectivities is the principal objective in synthetic chemistry. Combining data science and organic synthesis to achieve this goal is an emerging trend, but few examples of successful reaction designs are reported. We developed an artificial neural network regression model using bond orbital data to predict chemical reactivities. Actual experimental verification confirmed cycloheptatriene-selective (6 + 2)-cycloaddition utilizing nitroso compounds and norcaradiene-selective (4 + 2)-cycloaddition reactions employing benzynes. Additionally, a one-pot asymmetric synthesis was achieved by telescoping the enantioselective dearomatization of non-activated benzenes and cycloadditions. Computational studies provide a rational explanation for the seemingly anomalous occurrence of thermally prohibited (6 + 2)-cycloaddition without photoirradiation.