The long-term objective of the research described in this proposal is the development of Pt- and Au- catalyzed protocols for the intramolecularhydrofunctionalization of unactivated alkenes and alleneswith carbon, nitrogen, and oxygen nucleophilesthat display the generality, efficiency and selectivity (chemo-, regio-, and stereo-) required for applicationto the synthesis of biologically relevant heterocyclic compounds in both academic and pharmaceutical environments.
Our specific aims for the tenure of this proposal are to 1) optimize and expand the scope of the platinum-catalyzedintramolecular hydroaminationof alkenyl amines and the gold-catalyzed hydroamination of N-alkenyl and N-allenyl carboxamide derivatives, 2) apply Pt- and Au-catalyzed hydroamination to the synthesis of bicyclic nitrogen compounds, cyclic carboxamide derivatives, and the alkaloids (+)-241D, (-)-Sedamine, and (-)-Allosedamine, 3) identify an effective catalyst system for the asymmetric hydroamination of allenes, 4) investigate the scope of the Au-catalyzed intramolecular hydroarylation of chiral allenyl alcohols, 5) optimize and expand the scope of the Au- catalyzed intramolecularasymmetric hydroalkoxylationof allenes, 6) apply catalytic asymmetric hydroalkoxylation to the desymmetrization of prochiral allenyl alcohols and to the synthesis of d-Nebivolol, 7) optimize and expand the scope of the catalytic hydroarylationof alkenes and allenes with electron-rich arenes and to apply catalytic hydroarylationto the synthesis of Milnamide C, 8) optimize and expand the scope of the intramolecular asymmetric hydroarylationof unactivated alkenes and allenes with electron-rich arenes. Drug design and pharmaceutical development rely on general, reliable, and selective methods for the generation of a diverse range of molecular sub-structures. For this reason, the development of new and efficient methods for the construction of a variety of molecular structures is of central importance in organic synthesis. The activities described in this proposal will lead to the development of new synthetic methods that will facilitate the development of new drug targets andpharmaceuticals.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM080422-02S1
Application #
7680801
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Schwab, John M
Project Start
2007-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
2
Fiscal Year
2008
Total Cost
$58,806
Indirect Cost
Name
Duke University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Mukherjee, Paramita; Widenhoefer, Ross A (2013) The regio- and stereospecific intermolecular dehydrative alkoxylation of allylic alcohols catalyzed by a gold(I) N-heterocyclic carbene complex. Chemistry 19:3437-44
Mukherjee, Paramita; Widenhoefer, Ross A (2012) Gold(I)-catalyzed enantioselective intramolecular dehydrative amination of allylic alcohols with carbamates. Angew Chem Int Ed Engl 51:1405-7
Butler, Kristina L; Tragni, Michele; Widenhoefer, Ross A (2012) Gold(I)-catalyzed stereoconvergent, intermolecular enantioselective hydroamination of allenes. Angew Chem Int Ed Engl 51:5175-8
Brooner, Rachel E McKinney; Widenhoefer, Ross A (2011) Stereochemistry and mechanism of the Bronsted acid catalyzed intramolecular hydrofunctionalization of an unactivated cyclic alkene. Chemistry 17:6170-8
Li, Hao; Lee, Seong Du; Widenhoefer, Ross A (2011) Gold(I)-Catalyzed Enantioselective Intramolecular Hydroamination of Allenes with Ureas. J Organomet Chem 696:316-320
Li, Hao; Song, Feijie; Widenhoefer, Ross A (2011) Gold(I)-Catalyzed Intramolecular Hydroamination of N-Allylic,N'-Aryl Ureas to form Imidazolidin-2-ones. Adv Synth Catal 353:955-962
Mukherjee, Paramita; Widenhoefer, Ross A (2011) Gold(I)-catalyzed intramolecular amination of allylic alcohols with alkylamines. Org Lett 13:1334-7
Brown, Timothy J; Widenhoefer, Ross A (2011) Synthesis and equilibrium binding studies of cationic, two-coordinate gold(I) ?-alkyne complexes. J Organomet Chem 696:
Toups, Kristina L; Widenhoefer, Ross A (2010) Platinum(II)-catalyzed intermolecular hydroamination of monosubstituted allenes with secondary alkylamines. Chem Commun (Camb) 46:1712-4
Mukherjee, Paramita; Widenhoefer, Ross A (2010) Gold(I)-catalyzed amination of allylic alcohols with cyclic ureas and related nucleophiles. Org Lett 12:1184-7

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