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Monday, March 21, 2005
Douglass Taber
University of Delaware

Rare Sugars Are Now Readily Available Chiral Pool Starting Materials

Many of the five- and six-carbon sugars, although well known, are rare, and too expensive to be used as chiral pool starting materials. David MacMillan of Caltech in an elegant series of papers (Angew. Chem. Int. Ed. 2004, 43, 2152, ; Science 2004, 305, 1752, ; Angew. Chem. Int. Ed. 2004, 43, 6722, .) has demonstrated a two-step route not just to protected six-carbon carbohydrates, but also to alkyl, thio and amino derivatives of those carbohydrates.

The key observation was that L-proline would catalyze the addition of α-hetero aldehydes to α-branched aldehydes such as 2 to give the aldol product 3 with high enantio- and diastereocontrol. Even more exciting, in the absence of other acceptors the α-hetero aldehydes dimerize with high relative and absolute stereocontrol. Both alkoxy and silyloxy aldehydes worked efficiently.

The second step in the hexose synthesis was the aldol condensation of 4 with another α-hetero aldehyde derivative 5. By tuning the Lewis acid and the solvent, three of the four possible diastereomeric products could be selectively prepared. α-Amino and α-thio aldehydes worked well also, leading to 9 and 10 respectively.

Proline catalysis leads to the anti products 3 and 4. Use of the designed imidazolidinone catalyst 11 leads to the complementary syn product 12.

D. F. Taber, Org. Chem. Highlights 2005, March 21.