Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 09, 2006
Douglass Taber
University of Delaware

Enantiocontrolled Construction of Oxygenated and Aminated Stereogenic Centers

Asymmetric synthesis depends substantially on the enantiocontrolled construction of oxygenated and aminated stereogenic centers.

One of the more exciting developments of recent years has been the development of enantioselective dialkyl zinc addition to aldehydes. These reagents are, however, challenging to handle. Simon Woodward of the University of Nottingham has now shown (Angew. Chem. Int. Ed. 2005, 44, 2232. DOI: 10.1002/anie.200462569) that complexation with DABCO converts readily-available trialkylaluminum reagents such as 1 to attentuated donors. BINOL-mediated additions of these reagents to aldehydes proceed with high enantiomeric excess.

Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo have reported (J. Am. Chem. Soc. 2005, 127, 4138. DOI: 10.1021/ja0507362) another family of easily-prepared nucleophiles, the alkenyl siloxanes. The catalyst for the addition is an enantiomerically-pure phosphine.

Patrick J. Walsh of the University of Pennsylvania has described (Org. Lett. 2005, 7, 1729. DOI: 10.1021/ol050255n) a complementary source of vinyl nucleophiles, based on alkenyl transfer from boranes such as 6. The product 7 can be protected, then hydrolyzed to the aldehyde.

Phase-transfer alkylation of the benzophenone imine of glycine ester remains a workhorse for the synthesis of α-amino acids. Merritt B. Andrus of Brigham Young University has developed (Tetrahedron Lett. 2005, 46, 3839. DOI: 10.1016/j.tetlet.2005.03.185) an improved dihydrocinchodine catalyst that delivers very good ee’s.

Another way to form a C-N bond is to directly aminate an enolate. Li Deng of Brandeis University has reported (Org. Lett. 2005, 7, 167. DOI: 10.1021/ol048190w) the remarkable observation that aryl cyanoacetates such as 11 can be aminated with high enantioselectivity to form the quaternary centers, again by using a quinine-derived organocatalyst.

Another asymmetric transformation with intriguing potential is the enantioselective sulfenylation of aldehydes reported (Angew. Chem. Int. Ed. 2005, 44, 794. DOI: 10.1002/anie.200462101) by Karl Anker Jørgensen of Aarhus University. Using a proline-derived organocatalyst, ternary centers are formed with high enantiomeric excess. This new availability of sulfides such as 14 raises the intriguing question of whether the aldehyde could be homologated without epimerization. If 15 could be prepared with high geometric and enantiomeric purity, Evans-Mislow rearrangement of the derived sulfoxide should deliver 16 also with high geometric and enantiomeric purity. The net transformation would be an interesting homologation of the aldehyde 13.

D. F. Taber, Org. Chem. Highlights 2006, January 9.