Conversion of phenols into chromens: regiospecificity and scope

Abstract

Regiospecificity of the pyridine-catalysed reaction of α-unsaturated aldehydes or acetals with phenols is discussed. It is proposed that, after selection of the acidic triggering hydroxy-group, retention of the delocalisation energy of attachments to the phenol plays an important part in deciding which o-quinone methide, and hence which chromen, ‘citrylidene’ type, or cyclol will form. Examples involving chelated systems and fused homo- and hetero-cyclic aromatic rings are illustrated, and pyridine-catalysed deuteriation is shown to be a useful indicator of the ability of a phenol to undergo conversion into a chromen, and of the position at which pyran formation occurs. Certain rearrangements of the Claisen type appear to follow an orientation pattern explicable in terms of similar considerations. In some systems, where requirements for retention of the delocalisation energy from two features conflict, both possible products are formed. When terminally unhindered reagents such as acrylaldehyde acetal or methyl vinyl ketone are employed, products from C-Michael addition by the phenol are found. Some experimental conditions influencing chromen formation are mentioned.