Enantioselective Construction of Single Stereogenic Centers

Single enantiomer synthesis is of increasing importance in pharmaceutical production. It is essential that practical and. scalable procedures be developed for controlling the absolute configuration of new stereogenic centers as they are formed. Severally particularly important developments have recently been reported. 

Erick Carreira of ETH Hdnggerberg has reported (Organic Lett. 2004, 6,4575) a catalytic procedure for the reduction of nitroalkenes such as 4 to the nitroalkane 5 with high enantiomeric excess. He has also reported (Angew. Chem. Int. Ed. 2005,44,612) that the enantiomerically-enriched nitroalkane can be converted to the corresponding nitrile 6 without loss of stereochemical purity. 

An alternative route to nitriles of high enantiomeric excess, based on the conjugate addition of Me,Si-CN to an activated amide 7, has been reported (J. Am. Chem. Soc. 2004,126,9928) by Eric Jacobsen of Harvard University. The key to success in this case was dual catalysis, with a chiral A1 complex and a chiral Er complex. 

Another advance in conjugate addition has been reported Organic Lett. 2004, 6,4877) by Toshiro Harada of Kyoto Institute of Technology. The organocatalyst 10 efficiently mediates the addition of ketene silyl acetals to enones such as 9. In this case, it was use of the dimethylsilyl group that led to success. 

The work on organocatalytic aldol condensation continues unabated. In a recent advance, Armando Cordova of Stockholm University has found Angew. Chem. Int. Ed. 2004,43, 6528) that (S)-proline also will catalyze the Mannich reaction with high enantiomeric excess. Acyclic ketones also participate efficiently. 

---