Jacobsen, Eric

Eric N. Jacobsen Department of Chemistry Harvard University 12 Oxford Street Cambridge MA 02138 USA... 

Submitted by Jay F. Larrow and Eric N. Jacobsen.1 Checked by Chris H. Senanayake, Ji Liu, and Ichiro Shinkai. 

The tetracyclic alkaloid quinine 1 and the diastereomeric alkaloid quinidine 2 share a storied history. Eric Jacobsen of Harvard recently completed (J. Am. Chem. Soc. 2004, 126, 706) syntheses of enantiomerically-pure 1 and of 2. For each synthesis, the key reaction for establishing the asymmetry of the target molecule was the enantioselective conjugate addition developed by the Jacobsen group. 

Continuing the theme of small molecules as catalysts for organic reactions, Eric Jacobsen of Harvard has reported (J. Am. Chem. Soc. 2004,126, 10558) the design of a peptide thiourea that mediates enantioselective Pictet-Spengler cyclization, e.g. of 1 to 2. 

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 AI complex and a chiral Er complex. 

Activated aziridines should be as useful as epoxides for carbon-carbon bond formation, with the advantage that the product will already incorporated the desired secondary aminated stercocentcr. To date, a general enantioselective method for the aziridination of alkcncs has not been developed. Eric Jacobsen of Harvard University (Angew. Chem. hit. Ed. 2004,43, 3952) has explored an interim solution, based on the resolution of racemic epoxides such as I. The cobalt catalyst that selectively hydrolyzes one enantiomer of the epoxide also promotes the addition of the imidc to the remaining enantiomerically-enriched epoxide. As expected, the aziridine 4 is opened smoothly with dialkyl cuprates. 

ERIC N. JACOBSEN ANDREAS PFALTZ HISASHI YAMAMOTO Editors... 

Eric N. Jacobsen Andreas Pfaltz Hisashi Yamamoto (Eds.)... 

Eric N. Jacobsen, Cambridge Andreas Pfaltz, Basel Hisashi Yamamoto, Chicago... 

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