Supersilyl Protective Groups in Aldol Reactions

Catalytic Asymmetric Iterative/Domino Aldehyde Cross-Aldol Reactions for the Rapid and Flexible Synthesis of 1,3-Polyols

“…Thus, the installation of a second 1,3-diol unit through iterative use of aldol reactions requires nonproductive steps; i.e., protection of the β-hydroxy group, followed by reduction and/or oxidation of the terminal carbonyl group to the corresponding aldehyde. An ideal unit reaction for 1,3-polyol synthesis is the catalytic asymmetric cross-aldol reaction between two different aldehydes, directly providing an aldehyde moiety for subsequent iterative aldol reactions (Figure A, upper row). Here we disclose catalytic asymmetric iterative/domino aldehyde cross-aldol reactions for the straightforward synthesis of enantiomerically and diastereomerically enriched 1,3-polyols.…”

“…To prevent the formation of the unreactive hemiacetals, hydroxy groups of the intermediates need to be protected in more than double-aldol reactions. Precedent examples for iterative aldehyde cross-aldol reactions are limited to the proline-catalyzed asymmetric aldol reaction, followed by a diastereoselective Mukaiyama aldol reaction, , the proline-catalyzed asymmetric double-aldol reaction with switching of the catalyst chirality to avoid microscopic reversibility, the engineered enzyme-catalyzed asymmetric double-aldol reaction, a catalytic diastereoselective (racemic) one-pot triple-aldol reaction, ,− and an enzyme-catalyzed asymmetric triple-aldol reaction . There is much room left for improvement in these pioneering examples especially with regard to the substrate generality and practicality.…”