A Hetero Diels–Alder Approach to the Synthesis of Chromans (3,4-Dihydrobenzopyrans) Using Oxonium Ion Chemistry: The Oxa-Povarov Reaction

An oxa analogue of the well-known Povarov reaction has
been developed
for the synthesis of 3,4-dihydrobenzopyrans (chromans). The reaction
involves the formal inverse electron demand [4 + 2] cycloaddition
reaction of in situ-generated cationic aryl 2-oxadiene oxocarbenium
ions with alkenes. The oxonium ion intermediates are generated through
Lewis acid (SnCl4)-promoted reactions of phenol-derived
Rychnovsky-type mixed acetals. The yield and diastereoselectivity
of the chroman products are found to depend upon the substitution
pattern of the precursor alkene (i.e., monosubstituted, trans- or
cis-disubstituted and cyclic alkenes). Generally, the reactions afford
the endo-diastereomers as the major products, except for the reactions
of trans-β-methylstyrene, which afford exo-chromans. A comparison of the product distributions
from the reactions of trans- and cis-β-methylstyrene reveal that the reaction proceeds, at least
in part, by a nonconcerted ionic pathway. Just as for the aza-Povarov
reaction, there are two potential mechanisms for the reaction. The
first mechanism involves a direct asynchronous [4 + 2] cycloaddition
pathway, while the second occurs through the stepwise Prins addition
of the alkene to the aryl 2-oxadiene oxonium ion, followed by an intramolecular
aromatic substitution reaction of the resultant cation (i.e., a domino
Prins/intramolecular Friedel–Crafts reaction).