Simple and practical direct asymmetric aldol reaction of hydroxyacetone catalyzed by 9-amino Cinchona alkaloid tartrates

Abstract

A novel organocatalytic procedure for the direct aldol reaction of unprotected acetol and activated aromatic aldehydes catalyzed by 9-amino-9-epi-Cinchona ditartrates is presented. The protocol presented avoids the use of problematic solvents and toxic reagents as well as chromatographic purification of the products – instead a simple extraction has been applied for the isolation of pure aldols from the reaction mixture. This catalytic system provides exclusively linear aldols with quantitative yields and good syn-diastereoselectivity and enantioselectvitiy up to 90% ee. Further upgrading of the enantiomeric excess of syn-aldols up to 99% ee is easily accomplished by a single and reliable crystallization. The use of cinchonine or quinine-derived catalysts gives access to both enantiomers of syn-aldols for which the absolute configuration has been determined by X-ray diffraction. The operationally convenient and scalable organocatalytic procedure using cheap and renewable chemicals – both acetol and the catalysts, offers a sustainable and green way for the synthesis of a number of α-keto-syn-diols.