Research

Our group’s research efforts range from total synthesis of bioactive natural products to asymmetric catalysis. In summary, we are interested both in devising concise and efficient strategies for synthesizing complex molecules and in designing simple molecules possessing desired chemical properties.

In 2004, we completed total syntheses of the unusual marine alkaloid sceptrin 1. In 2007, we disclosed a regioselective synthesis of antibiotic prekinamycin 2, utilizing a novel annulation reaction, and an enantioselective synthesis of alkaloid lobeline 3 via desymmetrization of a meso-diol precursor using one of our catalysts, BTM 7 (see below). Currently, we are concentrating on the recently isolated cytotoxic metabolite cephalimysin 4.

Our efforts in the area of asymmetric catalysis concentrate on enantioselective acyl transfer. Over the past several years, we have developed four successive generations of a new class of enantioselective acyl transfer catalysts (5-8). These compounds, easily obtained from commercially available starting materials, are highly effective in kinetic resolution of several classes of chiral secondary alcohols. In addition, we have demonstrated for the first time kinetic resolution of chiral lactams, e.g., oxazolidinones, via catalytic, enantioselective N-acylation. The enantioselectivities observed in all these cases are consistent with a transition state model based on pi-pi and cation-pi interactions between the acylated intermediate and the substrate (e.g., 9). Our recent computational studies in collaboration with the Houk group (UCLA) support this hypothesis.

In addition, we have recently discovered that the salts of 1,2,4-triazole are active anionic acyl transfer catalysts suitable for the aminolysis and transesterification of esters. For example, in the presence of DBU triazolide isopropenyl acetate can be used as a mild acetylating agent producing acetone as the only byproduct. The same catalyst also promotes the aminolysis of unactivated esters, including the cyclocondensation of methyl esters of alpha-amino acids. We are currently exploring asymmetric catalyst designs incorporating the triazole moiety with the aim of developing catalytic kinetic resolution of amines.

Apart from our studies on acyl transfer, we have developed a new class of stoichiometric chiral hypervalent iodine reagents oxidizing o-alkylphenols with significant levels of asymmetric induction. The intermediate o-quinols thus generated undergo spontaneous Diels-Alder dimerization with complete regio- and diastereoselectivity producing tricyclic final products adorned with 6 stereocenters. Compounds of this type have been found in Nature.

Selected Publications

• Birman, V. B.; Jiang, X. "Synthesis of sceptrin alkaloids," Org. Lett. 2004, 6, 2369.
• Birman, V. B.; Uffman, E. W.; Jiang, H.; Li, X.; Kilbane, C. J. "2,3-dihydroimidazo[1,2-a]pyridines: a new class of enantioselective acyl transfer catalysts and their use in kinetic resolution of alcohols", J. Am. Chem. Soc. 2004, 126, 12226.
• Birman, V. B.; Jiang, H. " Kinetic Resolution of Alcohols Using a 1,2-Dihydroimidazo[1,2-a]quinoline Enantioselective Acylation Catalyst" Org. Lett. 2005, 7, 3445.
• Birman, V. B.; Li, X. " Benzotetramisole: A Remarkably Enantioselective Acyl Transfer Catalyst" Org. Lett. 2006, 8, 1351.
• Birman, V. B.; Jiang, H.; Guo, L.; Li, X.; Uffman, E. W. "Kinetic Resolution of 2-Oxazolidinones via Catalytic, Enantioselective N-Acylation" J. Am. Chem. Soc. 2006, 128, 6536.
• Birman, V. B.; Zhao, Z.; Guo, L. "Benzo[b]fluorenes via Indanone Dianion Annulation. A Short Synthesis of Prekinamycin" Org. Lett. 2007, 9, 1223.
• Birman, V. B.; Jiang, H.; Li, X. "Enantioselective Synthesis of Lobeline via Nonenzymatic Desymmetrization" Org. Lett. 2007, 9, 3237.
• Birman, V. B.; Li, X. "Homobenzotetramisole: An Effective Catalyst for Kinetic Resolution of Arylcycloalkanols" Org. Lett. 2008, 10, 1115.
• Li, X.; Liu, P.; Houk, K. N.; Birman, V. B. "Origin of Enantioselectivity in CF3-PIP-Catalyzed Kinetic Resolution of Secondary Benzylic Alcohols" J. Am. Chem. Soc. 2008, 130, 13836.
• Boppisetti, J. K.; Birman, V. B. "Asymmetric Oxidation of o-Alkylphenols with Chiral 2-(o-Iodoxyphenyl)-oxazolines" Org. Lett. 2009, 11, 1221.
• Yang, X.; Birman, V. B. " Acyl Transfer Catalysis with 1,2,4-Triazole Anion " Org. Lett. 2009, 11, 1499.