Chemistry Weekly Seminar - Dr. Dale Ward

Selective synthesis of sets of diastereomers from common reactants is a current challenge in synthetic chemistry.[1] Polypropionate syntheses typically rely on methods that produce only 1-2 stereocenters per C-C bond forming step and have limited potential to selectively generate stereochemical diversity, particularly when chiral fragments are coupled.[2] We have been developing a general strategy for the rapid assembly of stereochemically diverse polypropionate motifs that exploits sequential enantiotopic group selective aldol reactions of achiral, meso, or chiral ketones with chiral aldehydes that generate 3 (or more) stereocenters per C-C bond forming step.[3,4] Here, we present largely unpublished work on how the design of the reactants can facilitate manipulation of the stereocontrol elements (diastereoface selectivity, relative topicity) and thereby permit selective access to a large number of diastereoisomers (e.g., 75% of all stereoheptads) in ≤7 steps from a small set of common building blocks. Recent applications of this strategy to the total syntheses of marine polypropionates will also be presented.