Chiral Separation of Spiro-compounds and Determination Configuration

Chiral spirocyclic compounds have attracted the attention of scholars and scientists owing to their potential applications in the pharmaceutical industry as either active pharmaceutical ingredients, catalysts in synthesizing active enantiomers, or as surface modifiers on silica particles to resolve entantiomers. In this study, five spiro compounds of 3,9-diphenyl-2,4,8,10-tetraoxaspiro[5.5]-undecane(1), 3,9-(4-methoxyphenyl)-2,4,8,10-tetraoxaspiro[5.5]-undecane(2), 3,9-(4-methylphenyl)-2,4,8,10-tetraoxaspiro[5.5]-undecane(3), 4,4′-(2,4-8,10-tetraoxaspiro[5.5]undccane-3,9-diyl)dibenzoic acid(4) and 3,9-di(4-formyl-phenyl)-2,4,8,10-tetraoxa-spiro[5.5]-undecane(5) were synthesized by grinding pentaerythritol with benzaldehyde, 4-methoxybenzaldehyde, 4-methylbenzaldehyde, 4-carboxybenzaldehyde or tcrephthalaldehyde monoacetal in the presence of InBr3 under solvent-free conditions. A normal phase HPLC method was successfully developed to resolve entantiomers of compounds 1-5 on a chiral column. Specific optical rotation of R or S enlantiomers(1) was determined and the corresponding configurations were proposed based on Lowe's rule.