Valence-isomer selective cycloaddition reaction of cycloheptatrienes-norcaradienes

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 develop an artificial neural network regression model using bond orbital data to predict chemical reactivities. Actual experimental verification confirms cycloheptatriene-selective 6 + 2-cycloaddition utilizing nitroso compounds and norcaradiene-selective 4 + 2-cycloaddition reactions employing benzynes. Additionally, a one-pot asymmetric synthesis is 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 suprafacial 6 + 2-cycloaddition without photoirradiation.