Uttam Tambar

Stereoselective Functionalization of Unsaturated Hydrocarbons

The selective functionalization of C-H bonds has revolutionized the chemical synthesis of complex molecules. Most strategies are based on metal-catalyzed C-H activation and C-H insertion processes. The Tambar Group is interested in developing a conceptually distinct approach to C-H functionalization that is based on selective pericyclic reactions. We are studying catalytic stereoselective reactions for the functionalization of unsaturated hydrocarbons.  We have developed a catalytic enantioselective allylic amination of unactivated alkenes via a [2,3]-rearrangement. In this method, a diimido-sulfur reagent serves as the source of nitrogen, and it reacts selectively with terminal alkenes through a hetero-ene reaction.  The resulting ene adduct undergoes a Pd-catalyzed enantioselective [2,3]-rearrangement to generate chiral amines in high enantiomeric excess. Based on this chemistry, we have developed a copper-catalyzed enantioselective allylic alkylation of unactivated alkenes with Grignard reagents to generate internal alkenes with high regioselectivity and E-selectivity. We have also discovered regioselective and diastereoselective aminoarylations and aminothiolations of 1,3-dienes with Grignard reagents that are based on a selective [4+2] cycloaddition.  These results represent a general strategy for functionalizing unsaturated hydrocarbons with aromatic, aliphatic, and vinyl Grignard reagents. As an extension of our approach to the catalytic allylic functionalization of unactivated terminal alkenes, we recently pursued the more challenging problem of catalytic asymmetric allylic functionalization of internal alkenes. We have developed an enantioselective, regioselective, and E/Z selective allylic oxidation of unactivated internal alkenes via a catalytic asymmetric hetero-ene reaction with an imido-sulfur oxidant.

References:

¹ Bao, H.; Tambar, U. K. J. Am. Chem. Soc. 2012, 134, 18495-18498.
² Bao, H.; Bayeh, L.; Tambar, U. K. Angew. Chem., Int. Ed. 2014, 53, 1664-1668.
³ Bao, H.; Bayeh, L.; Tambar, U. K. Chem. Sci. 2014, 5, 4863-4867.
⁴ Sleet, C. S.; Tambar, U. K. Angew. Chem., Int. Ed. 2017, 56, 5536-5540.
⁵ Bayeh, L.; Le, P. Q. Tambar, U. K. Nature 2017, 546, 196-200.

Uttam K. Tambar moved from India to the United States in 1982.  He received his A.B. degree from Harvard University in 2000 and his Ph.D. from the California Institute of Technology in 2006 with Professor Brian Stoltz.  After he completed his NIH Postdoctoral Fellowship at Columbia University with Professor James Leighton in 2009, he began his independent research career at UT Southwestern Medical Center in Dallas.  He is currently an Associate Professor in the Biochemistry Department and a W. W. Caruth, Jr. Scholar in Biomedical Research.  The Tambar lab is interested in asymmetric catalysis, natural product synthesis, and medicinal chemistry.

Homepage: http://www.utsouthwestern.edu/labs/tambar/
Twitter: @TambarLab

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Wed. Sep. 19 | 9.30am – Invited Speaker.