Enantioselective Assembly of Aminated Stereogenic Centers

Although natural amino acids are readily available, there is a continuing need for unnatural amino acids. Jon C. AntiUa of the University of South Florida has described J. Am. Chem. Soc. 2007,129, 5830) a promising approach, based on the enantioselective organocatalytic reduction of imines such as 1 derived from a-keto esters. The aryl group is easily removed to give the primary amine. 

Mukund P. Sibi of North Dakota State University has developed (J. Am. Chem. Soc. 2007, 129, 4522) an enantioselective Mg catalyst that mediated the addition of benzyl hydrazine 6 to imides such as 5. The initial adduct cyclized to the pyrazolidinone 7. Karl Anker Jorgensen of Aarhus University has repotted (Angew. Chem. Int. Ed. 2007, 46, 1983) a complementary protocol for the enantioselective conjugate addition of a nitrogen nucleophile. 

Enantioselective homologation can also be a powerful approach. Benjamin List of the Max-Planck-Institute, Miilheimhas foimd (Angew. Chem. Int. Ed. 2007, 46, 612 Organic Lett. 2007, 9, 1149) that three-component coupling of acetyl cyanide, an aldehyde and benzylamine under the influence of the Jacobsen thiourea catalyst 10 delivered the one-carbon homologated nitrile 12 in high ee. 

Other homologation methods are also effective. Li Deng of Brandeis University has shown (Organic Lett. 2007, 9, 603) that imder the influence of cinchona-derived quaternary 

Other routes to enantiomerically-pure amines have been put forward. Knowing that CAL-B would selectively acylate just the R enantiomer of the racemic a-methyl primary amine 22, Stephane Gastaldi, Gerard Gil and Michele P. Bertrand of the Universite Paul Cezanne devised (Organic Lett. 2007, 9, 837) a thiyl-based method for equilibrating 22, leading to a net deracemizing acylation. 

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