This research proposal is concerned with the development of new synthetic methods and applications of the type 2 intramolecular Diels-Alder reaction. The type 2 intramolecular Diels-Alder reaction and the resulting anti-Bredt olefins have found application in organic synthesis. The constraints resulting from the connectivity in the Diels-Alder precursor creates a strong regio- and stereochemical bias in the cycloaddition step. The end result of this bias is the stereoselective synthesis of highly substituted carbocyclic and heterocyclic rings. The utility of this reaction has been demonstrated in recent applications of the type 2 IMDA reaction as a key step in the total synthesis of complex natural products. The proposal contains three sections; 1) the development of asymmetric catalysts for the type 2 IMDA reaction; 2) an exploration of the type 2 intramolecular acyl nitroso Diels-Alder cycloaddition and related heteroatom reactions, and 3) the synthesis and chemistry of bridgehead allyl silanes. The synthetic methods and novel polycyclic structures that will result from this research will enhance the utility of this transformation and provide powerful tools for the synthesis of biologically important compounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM071492-03
Application #
7210588
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2005-04-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$243,659
Indirect Cost
Name
University of California Irvine
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Cleary, Leah; Yoo, Hoseong; Shea, Kenneth J (2011) Microwave assisted synthesis of bridgehead alkenes. Org Lett 13:1781-3
Rodriguez, Andrew A; Zhao, Carrie; Shea, Kenneth J (2009) Asymmetric bisboranes as bidentate catalysts for carbonyl substrates. Org Lett 11:713-5
Rodriguez, Andrew A; Yoo, Hoseong; Ziller, Joseph W et al. (2009) New Architectures in Hydrogen Bond Catalysis. Tetrahedron Lett 50:6830-6833
Brailsford, John A; Lauchli, Ryan; Shea, Kenneth J (2009) Synthesis of the bicyclic welwitindolinone core via an alkylation/cyclization cascade reaction. Org Lett 11:5330-3
Molina, Claudia L; Chow, Chun P; Shea, Kenneth J (2007) Type 2 intramolecular N-acylazo Diels-Alder reaction: regio- and stereoselective synthesis of bridgehead bicyclic 1,2-diazines. J Org Chem 72:6816-23