Chemistry Weekly Seminar - Sushital Jana

Title:

STEREOSELECTIVE SYNTHESIS OF FELKIN AND NON-FELKIN ALDOLS

The key step in polypropionate natural product syntheses involves coupling of two non-racemic fragments. The individual biases associated with each fragment can be reinforcing (matched) or opposing (mismatched) in an aldol coupling. Instances have been reported where either surprisingly low diastereoselectivities were obtained or formation of stereoisomers inconsistent with the prediction were observed. Thus, retrosynthetic analysis requires judicious selection of a strategic bond for disconnection in which the outcome for the forward reaction can be accurately predicted. To avoid the coupling of two non-racemic fragments, the Ward Group has developed aldol couplings which proceed with kinetic resolution (only one reactant non-racemic). This strategy provided two (Felkin) of eight possible diastereomers resulting from the aldol coupling. To increase the stereochemical diversity, this strategy was further extended to acyclic ketones and the remaining two Felkin aldols were obtained selectively. All previous efforts to obtain the non-Felkin aldols under kinetic control have failed. Alternatively, retroaldol-aldol isomerization of Felkin aldols via their Mg(II)-aldolates provided access to two of four possible non-Felkin aldols. Observed diastereoselectivities were correlated with the chelating ability of the aldehyde component of the aldol adduct. It is now possible to selectively access six of the eight possible diastereomers in their non-racemic form with good yields and diastereoselectivities. These aldols are useful in polypropionate syntheses.