Tandem reactions have become a popular method for the synthesis of complex molecules from simple starting materials. Those involving transition metals as catalysts have become especially prevalent because of the low catalyst loadings, the potential for asymmetric induction with chiral ligands, and the ease with which they construct polycyclic carbocycles and heterocycles. The focus of this proposal is the development of an enantioselective three-component transition metal-catalyzed C-H insertion reaction between an aryl imine, a tethered olefin, and an exogenous olefin or alkyne to afford annulated products. To achieve this goal, readily available substrates will be synthesized and exposed to a transition metal and chiral ligand. A survey of temperature, solvent, and concentration will be performed in order to determine the optimal conditions for this process. This three-component reaction will provide access to complex polycyclic carbocycles and heterocycles from inexpensive starting materials. This proposal will no doubt improve upon existing C-H bond functionalization methodology and will provide the pharmaceutical industry with useful, new tools for the synthesis of bioactive targets.

Public Health Relevance

The development of a three-component tandem reaction will provide rapid access to complex structures from simple starting materials. The methods that will be developed have the potential to enable the very efficient synthesis of drug candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32GM090661-02
Application #
8070225
Study Section
Special Emphasis Panel (ZRG1-F04A-B (20))
Program Officer
Marino, Pamela
Project Start
2010-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$45,590
Indirect Cost
Name
Yale University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Phillips, Eric M; Mesganaw, Tehetena; Patel, Ashay et al. (2015) Synthesis of ent-ketorfanol via a C-H alkenylation/torquoselective 6? electrocyclization cascade. Angew Chem Int Ed Engl 54:12044-8
Ischay, Michael A; Takase, Michael K; Bergman, Robert G et al. (2013) Unstabilized azomethine ylides for the stereoselective synthesis of substituted piperidines, tropanes, and azabicyclo[3.1.0] systems. J Am Chem Soc 135:2478-81