The primary objective of this project is to develop new synthetic methodology based on reactions of organometallic complexes with organic substrates. The work particularly emphasizes development of new reactions using simple model systems coupled with thorough mechanistic studies. This approach provides new methodology for use in synthesis as well as a broad, general understanding of the ways in which transition metal complexes may be used to control organic reactions including regio- , stereo- and enantioselectivity.
One specific aim of the work is to use nucleophilic, electron-rich organomanganese and organoiron complexes to effect coupling with carbon electrophiles via addition of the electrophile to the metal center followed by migration to the pi-bound organic ligand. Using this general approach, methods will be developed for (a) regio- and stereocontrolled electrophilic substitutions of dienes, (b) stepwise, regioselective electrophilic substitutions of arenes and (c) coupling of substituted pi-allyl groups to carbon electrophiles with regioselectivity controlled via choice of metal ligands. A second aspect of the project will focus on reactions of electrophilic chiral-at-iron carbene complexes. Routes to several optically pure iron carbene complexes will be devised. These complexes will then be used to develop new enantioselective syntheses of alcohol and ethers, epoxides, aziridines and alpha-lithioethers. Mechanistic studies will be aimed at revealing the basis for enantioselection and how variations in ligand environment control enantioselectivity. New reactions developed will complement existing synthetic methodology and should be applicable to the preparation of a diverse class of naturally occurring and/or biologically active systems. For example, the regio- and stereospecific electrophilic substitution of dienes could provide methods for the synthesis of intermediates which are readily converted by Diels-Alder reactions to aspidosperma alkaloids and cytochalasans, compounds which affect a range of biological processes including cell movement, platelet aggregation, cytokinesis and phagocytosis. The chiral iron systems can provide several enantiomerically pure chiral """"""""building blocks"""""""" which can be used in synthesis. The enantioselective cyclopropanation reaction will supply methodology for preparation of a variety of naturally occurring compounds containing cyclopropane rings. Such reagents are particularly attractive for use in synthesizing calysterols, naturally occurring steroids containing monomethyl-substituted cyclopropane and cyclopropene rings.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028938-11
Application #
3276336
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1981-07-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
11
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Arts and Sciences
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Bolig, Andrew D; Lyons, Thomas W; DiSalvo, Darren T et al. (2016) Intramolecular Hydrogen Transfer Reactions Catalyzed by Pentamethylcyclopentadienyl Rhodium and Cobalt Olefin Complexes: Mechanistic Studies. Polyhedron 103:51-57
Park, Sehoon; Brookhart, Maurice (2010) Hydrosilation of Carbonyl-Containing Substrates Catalyzed by an Electrophilic ?-Silane Iridium(III) Complex. Organometallics 29:6057-6064
Findlater, Michael; Bernskoetter, Wesley H; Brookhart, Maurice (2010) Proton-catalyzed hydrogenation of a d(8) Ir(I) complex yields a trans Ir(III) dihydride. J Am Chem Soc 132:4534-5
Bernskoetter, Wesley H; Schauer, Cynthia K; Goldberg, Karen I et al. (2009) Characterization of a rhodium(I) sigma-methane complex in solution. Science 326:553-6
Bernskoetter, Wesley H; Hanson, Susan Kloek; Buzak, Sara K et al. (2009) Investigations of iridium-mediated reversible C-H bond cleavage: characterization of a 16-electron iridium(III) methyl hydride complex. J Am Chem Soc 131:8603-13
Bolig, Andrew D; Brookhart, Maurice (2007) Activation of sp3 C-H bonds with cobalt(I): catalytic synthesis of enamines. J Am Chem Soc 129:14544-5
Roy, Amy H; Lenges, Christian P; Brookhart, Maurice (2007) Scope and mechanism of the intermolecular addition of aromatic aldehydes to olefins catalyzed by Rh(I) olefin complexes. J Am Chem Soc 129:2082-93
Gottker-Schnetmann, Inigo; Heinekey, D Michael; Brookhart, Maurice (2006) Temperature- and solvent-dependent binding of dihydrogen in iridium pincer complexes. J Am Chem Soc 128:17114-9
Sykes, Alison Cartwright; White, Peter; Brookhart, Maurice (2006) Reactions of Anilines and Benzamides with a Fourteen-Electron Iridium(I) Bis(Phosphinite) Complex: N-H Oxidative Addition versus Lewis Base Coordination. Organometallics 25:1664-1675
Gottker-Schnetmann, Inigo; Brookhart, Maurice (2004) Mechanistic studies of the transfer dehydrogenation of cyclooctane catalyzed by iridium bis(phosphinite) p-XPCP pincer complexes. J Am Chem Soc 126:9330-8

Showing the most recent 10 out of 14 publications