Synthesis of C4 - C5 cycloalkyl-fused and C6-modified chromans via ortho-quinone methides.

Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-cycloalkyl-fused and 6-modified chromans could be prepared via ortho-quinone methides (o-QMs)/hetero-Diels-Alder (HDA) reactions of the appropriate precursors. The bromide at C6 served as a handle for introducing other substituents through palladium-catalyzed cross-coupling reactions and other functional-group transformations. Moderate to high yields (up to 80%) and diastereoselectivities (up to >99:1) could be obtained under [PtCl4] catalysis. The preferred endo transition state during the cycloaddition reaction played an important role in governing the stereochemical outcomes at C2C3C4. The configurationally fixed E geometry of the bicyclic o-QMs influenced the cycloaddition reactions to favor the C2C4 cis relationship.