Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 23, 2004
Douglass Taber
University of Delaware

Enantioselective C-C Bond Construction: Part Two of Three

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high ee by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 2003, 68, 5668. DOI: 10.1021/jo0342875) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% ee by a single recrystallization.

The coupling of the racemic allylic acetate 4 with malonate can give either the terminal product 5 or the internal product 6. Tamio Hayashi of Kyoto University reports (Organic Lett. 2003, 5, 1713. DOI: 10.1021/ol0343562) that using a Rh catalyst in the presence of Cs2CO3 and a chiral phosphine leads to a 1:99 ratio in favor of the internal product 6, with outstanding ee.

Starting with the racemic carbonate 7 and using a Mo catalyst, Christina Moberg of the Royal Institute of Technology (KTH) in Stockholm was able to achieve (Organic Lett. 2003, 5, 2275. DOI: 10.1021/ol034605m) 26:1 regioselectivity in favor of the branched product 9, again with outstanding ee. In this case, the pyridylamide ligand for the Mo is polymer-bound, so it is easily recycled. Remarkably, this high ee was observed for reactions run at elevated temperature with microwave promotion (6 minutes, 160C).

Albert S.C. Chan of the Hong Kong Polytechnic University reports (J. Org. Chem. 2003, 68, 1589. DOI: 10.1021/jo026551k) two important transformations. The three-component (Mannich) condensation of 10 with 11 and 12 proceeds with high diastereoselectivity, to give the amino alcohol 13. Hydroboration of the alkyne 14 followed by transmetalation of the intermediate vinyl borane gives a zinc species, which under catalysis by the easily-prepared β-naphthol 13 adds to aromatic and branched aldehydes with high ee. The product allylic alcohols are useful intermediates for organic synthesis.

D. F. Taber, Org. Chem. Highlights 2004, August 23.