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.

Norcaradiene–Cycloheptatriene Equilibrium: A Heavy-Atom Quantum Tunneling Case

“…The norcaradiene­( 1 )–cycloheptatriene­( 2 ) equilibrium involves an orbital-symmetry allowed pericyclic reaction, which still raises questions despite a long odyssey of experiment and theory aimed at identifying the norcaradiene. This disrotatory electrocyclic reaction (Scheme ) has garnered the interest of chemists for more than half a century. − …”

“…This disrotatory electrocyclic reaction ( Scheme 1 ) has garnered the interest of chemists for more than half a century. 2 − 4 …”

“… 3 The key strategy involves a one-step Diels–Alder reaction intercepting in situ-generated norcaradiene ( Scheme 2 a). More recently, a series of valence-isomer selective cycloaddition reactions of cycloheptatriene-norcaradiene have been disclosed, 4 namely the anomalous thermally forbidden suprafacial [6 + 2]-cycloadditions with nitroso compounds and norcaradiene-selective [4 + 2]-cycloadditions employing benzynes ( Scheme 2 b).…”

Copper-Catalyzed Dearomative trans-1,2-Carboamination

“…Methods involving rapid and controlled conversion of simple and readily available arenes into compounds of greater complexity are central to organic synthesis. While the field of arene functionalization has seen significant advances, ranging from C–H activation to novel electrophilic reagents, dearomative functionalizations are much less developed . The inherent resonance stabilization coupled with kinetic challenges of trapping fleeting intermediates have hindered methodological development of new dearomative processes.…”