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,
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 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.