Highly diastereoselective tandem photoenolization-hetero-Diels-Alder cycloaddition reactions of o-tolualdehydes in...

The (E)-photoenols generated in situ by photolysis of o-tolualdehydes 1-5 in the solid state react with the precursor aldehydes as dienophiles in a hetero-Diels-Alder cycloaddition fashion to afford trans-3-arylisochromanols in excellent yields and in a high diastereoselectivity. An examination of the reactivity of three different classes of rationally designed aldehydes shows that the tandem enolization-Diels-Alder cycloaddition occurs in the solid state efficiently for aldehydes whose (E)-photoenols (i) are more stable than their corresponding benzocyclobutenols and (ii) are not sterically congested. However, rapid cyclization to benzocyclobutenols is found to be the sole pathway for sterically encumbered (E)-enols derived from aldehydes 6-8. Given that the execution of heteromolecular reactions in the solid state is a challenge, the results obtained with simple crystalline o-tolualdehydes are remarkable and the strategy involving in situ generation of a dienol in the crystal lattice of a dienophile to achieve hetero-Diels-Alder reaction in a highly diastereoselective manner is heretofore unprecedented. In the context of enormous interest in tandem/domino reactions in contemporary synthetic organic chemistry, the results observed with o-tolualdehydes exemplify successful execution of tandem reactions in the solid state.