Molecular design principles towards exo-exclusive Diels–Alder reactions

The exo selective Diels–Alder reactions, reported as special cases, usually involve catalytic reaction conditions and specific cyclic structural motifs on the diene and/or the dienophile. Here we report a systematic computational investigation on the substituent effect for simple, linear dienes and dienophiles towards exo control in Diels–Alder reactions under thermal conditions. Through detailed characterization of reaction pathways for Diels–Alder cycloadditions between linear dienes and dienophiles with various substituents, we summarize a set of design principles aiming for an optimal and nearly-exclusive exo selectivity. These results shall lead to valuable guidelines and more versatile strategies in organic synthesis that are in accordance with the principles of green chemistry.