Enantioselective Construction of Alkylated Centers

Unsaturated half acid esters such as 1 are readily prepared by Stobbe condensation between dialkyl succinate and an aldehyde. Johannes G. de Vries of DSM and Floris P. J. T. Rutjes of Radboud University Nijmegen observed (Adv. Synth. Catal. 2008, 350, 85) that these acids were excellent substrates for enantioselective hydrogenation. Kazuaki Kudo of the University of Tokyo designed Organic Lett. 2008,10,2035) a resin bound peptide catalyst for the transfer reduction of unsaturated aldehydes such as 3, using 4 as the net donor. Note that 5 was produced with high enantiocontrol from 3 that was a 2 1 mixture of geometric isomers. 

Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo devised (J. ArtL Chem. Soc. 2008,130, 6072) a chiral Gd catalyst that mediated the conjugate cyanation of enones such as 6 with high ee. Eric N. Jacobsen of Harvard University prepared Angew. Chem. Int. Ed. 2008,47,1762) a dimeric A1 salen catalyst that showed improved activity over the monomeric catalysts. Even congested imides such as 8 could be cyanated efficiently, delivering alkylated quaternary stereogenic centers. 

Using a designed catalytic peptide, Hehna Wennemers of the University of Basel alkylated (J. Am. Chem. Soc. 2008,130, 5610) aldehydes such as 33 withnitroethylene. Samuel H. GeUman of the University of Wisconsin effected (J. Am. Chem. Soc. 2008,130, 5608) the same transformation using the catalyst 27. Professor Wennemers showed that reduction of 35 followed by Mioskowski oxidation of the nitro group to the acid delivered the y-lactone 36. Enantiomerically-pure y-lactones such as 36 are powerful intermediates for the enantioselective construction of natural products. 

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