Regioselectivity in the Syntheses of Enantiopure 2-Benzopyrans through Intramolecular Cyclization of Tethered Lactaldehydes. Conformations of the Products

Abstract

Using titanium tetraisopropoxide, the enantiopure tethered lactaldehyde (α′ S,2S)-2-(3′-hydroxy-α′-methyl-benzyloxy)propanal (6) is cyclized with complete regio- and diastereoselectivity ortho to the phenolic hydroxyl group to give (1S,3S,4R)-3,4-dihydro-1,3-dimethyl-2-benzopyran-4,5-diol (7). Similar cyclization of the epimeric (α′ R,2S)-lactaldehyde (25) yields solely the corresponding (1R,3S,4R)-4,5-diol (34). The 4,5-diacetate (26), but not (35), undergoes conformational inversion of the heterocyclic ring through significant 4,5-peri interactions between the adjacent acetoxy substituents. Spontaneous cyclizations of the corresponding phenoxide ions of the lactalde-hydes (6) and (25), generated by fluoride from their silyl ethers, led to the related 4,7-diols with high regioselectivity through ring-closure para to the aromatic oxygen.