Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 21, 2005
Douglass Taber
University of Delaware

Enantioselective Construction of Aldol Products: Part Two of Two

Acyclic stereoarrays are important both in themselves and as precursors to enantiomerically-defined ring systems. Although the aldol condensation has for many years been a workhorse for acyclic stereoselection, there are still new things that can be done.

In a pair of papers last year, Scott Nelson of the University of Pittsburgh expanded the range of the ketene “aldol”. In the first paper (J. Am. Chem. Soc. 2004, 126, 14. DOI: 10.1021/ja0391208), he employed a chiral Al-based catalyst 3. This catalyst mediated additions such as propionyl bromide 1 to 2 to give 4 in 98:2 syn/anti ratio and 95% ee.

In a follow-up paper (J. Am. Chem. Soc. 2004, 126, 5352. DOI: 10.1021/ja0492900), Professor Nelson used the commercially-available base quinaldine 7a (R=H) or its TMS ether 7b (R=TMS). Catalysts 7a and 7b are both efficient and give > 95% ee, but lead to opposite absolute configurations of the products. As with catalyst 3, the syn aldol product predominates, but now branched aldehydes such as 6 also participate efficiently in the reaction. This is another example of enantioselective catalysis by a small organic molecule.

Mukund Sibi of North Dakota State University has developed (J. Am. Chem. Soc. 2004, 126, 718. DOI: 10.1021/ja039087p) a powerful three-component coupling, combining an α,β-unsaturated amide 9, a hydroxylamine 10, and an aldehyde 11. The hydroxylamine condenses with the aldehyde to give the nitrone, which then adds in a dipolar sense to the unsaturated ester. The reaction proceeds with high diastereocontrol, and the absolute configuration is set by the chiral Cu catalyst. As the amide 9 can be prepared by condensation of a phosphonacetate with another aldehyde, the product 12 can be seen as the product of a four-component coupling, chirally-controlled aldol addition and Mannich condensation on a starting acetamide.

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