Direct catalytic asymmetric synthesis of highly functionalized 2-methylchroman-2,4-diols via Barbas-list aldol reaction

Abstract

A study was conducted to demonstrate the organocatalytic approach to the asymmetric synthesis of functionalized 2-methylchroman-2,4-diol products through 'Barbas-List aldol (BLA) reactions'. Investigations were conducted on the BLA reactions by screening a number of novel organocatalysts for the aldolization of 2-hydroxybenzaldehyde 2a by 14 to 28 equivalents of acetone. It was found that the BLA reaction proceeded in good yields with high selectivity using trans-4-OH-L-proline as the catalyst. The application of chiral aldol-lactol products 4/5 was demonstrated in the synthesis of highly functionalized molecules. Efforts were made to utilize chiral 2-methylchroman-2,4-diols as intermediates for the bioactive molecular synthesis.