The PI notes that the major goal of this work is to develop new techniques for the efficient formation of carbon-carbon bonds which can be used for the synthesis of biologically and pharmaceutically interesting molecules, pharmaceutical manufacturing and combinatorial chemistry. A particular focus of this work is to be the development of chemistry which employs simple, readily available building blocks which can be efficiently combined to prepare complex structures. It is indicated that in addition to the development of fundamentally new techniques of use in organic synthesis, issues which relate to cost, efficiency, safety and ease of use are to be of importance. The PI states that the work includes: 1) the study of the use of intramolecular insertion reactions of zirconocene and titanocene complexes of arynes to prepare tricyclic metallacycles as a means for the synthesis of indoles and related heterocycles; 2) the development of simple techniques for the preparation of polysubstituted aromatics. He notes that included will be the development of methods to regioselectively convert monosubstituted aromatics into trisubstituted aromatics and tetrasubstituted aromatics; 3) the study of catalytic coupling of small organic fragments into a variety of carbocycles and heterocycles using titanium, nickel and zirconium catalysts; 4) the development of catalytic processes for the asymmetric hydrofunctionalization of olefins to selectively prepare a variety of polyfunctionalized, enantiomerically enriched compounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034917-13
Application #
2608835
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1985-04-01
Project End
2000-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Hyde, Alan M; Buchwald, Stephen L (2009) Synthesis of 5,5-disubstituted butenolides based on a Pd-catalyzed gamma-arylation strategy. Org Lett 11:2663-6
Chieffi, A; Kamikawa, K; Ahman, J et al. (2001) Catalytic asymmetric vinylation of ketone enolates. Org Lett 3:1897-900
Tomori, H; Fox, J M; Buchwald, S L (2000) An improved synthesis of functionalized biphenyl-based phosphine ligands. J Org Chem 65:5334-41
Hundertmark, T; Littke, A F; Buchwald, S L et al. (2000) Pd(PhCN)(2)Cl(2)/P(t-Bu)(3): a versatile catalyst for Sonogashira reactions of aryl bromides at room temperature. Org Lett 2:1729-31
Broene, R D; Buchwald, S L (1993) Zirconocene complexes of unsaturated organic molecules: new vehicles for organic synthesis. Science 261:1696-701