This proposal is directed toward the understanding of the mechanisms of catalytic asymmetric processes and the design and development of chiral transition metal based catalysts to be used in asymmetric catalysis. The impacts of chiral synthetic technology are quite diverse and are critical to the fields of medicinal chemistry and pharmaceutical chemistry.
The specific aims of this proposal are: (I) To understand the structure, properties and reactivity of chiral bissulfonamido complexes and their role in asymmetric catalysis, (II) To synthesize (bissulfonamido)TiX2 complexes (X=F, C1, Br) and their base adducts, (III) To explore the synthesis, structure and reactivity of bissulfonamido titanium bisamide complexes which are versatile intermediates for the preparation of (bissulfonamido)titanium species, and (VI) to develop hexadentate titanium bissulfonamide compounds and apply them to asymmetric catalysis. Our long-term objective is to develop an understanding of the mechanism of chirality transfer in established asymmetric processes in order to build a foundation for the rational design of new asymmetric reactions. The course of asymmetric synthesis has been driven by an increase in the demand for optically pure materials. As result, much of the focus of this field has turned to improving methods to screen catalysts in asymmetric processes. However, rarely is the catalytic system understood and often little is known of the structure or the operation of the catalyst. The methods that we use to accomplish our goals involve the independent synthesis of proposed catalysts in asymmetric reactions and their characterization (including structurally). These complexes are then tested in the asymmetric process to evaluate their viability as catalysts.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM058101-02
Application #
6019481
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1998-09-01
Project End
2003-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Stanton, Gretchen R; Kauffman, Meara C; Walsh, Patrick J (2012) Diastereoselective chelation-controlled additions to ?-silyloxy aldehydes. Org Lett 14:3368-71
Hernandez-Toribio, Jorge; Hussain, Mahmud M; Cheng, Kevin et al. (2011) Diastereoselective aziridination of 2-B(pin)-substituted allylic alcohols: an efficient approach to novel organoboron compounds. Org Lett 13:6094-7
Zhang, Jiadi; Stanciu, Corneliu; Wang, Beibei et al. (2011) Palladium-catalyzed allylic substitution with (?6-arene-CH2Z)Cr(CO)(3)-based nucleophiles. J Am Chem Soc 133:20552-60
Hussain, Mahmud M; Hernandez Toribio, Jorge; Carroll, Patrick J et al. (2011) Synthesis of 2-keto-anti-1,3-diols by chemoselective tandem oxidation of 2-B(pin)-substituted allylic alcohols. Angew Chem Int Ed Engl 50:6337-40
Hussain, Nusrah; Hussain, Mahmud M; Ziauddin, Muhammed et al. (2011) Stereoselective vinylation of aryl N-(2-pyridylsulfonyl) aldimines with 1-alkenyl-1,1-heterobimetallic reagents. Org Lett 13:6464-7
Cheng, Kevin; Carroll, Patrick J; Walsh, Patrick J (2011) Diasteroselective preparation of cyclopropanols using methylene bis(iodozinc). Org Lett 13:2346-9
Stanton, Gretchen R; Koz, Gamze; Walsh, Patrick J (2011) Highly diastereoselective chelation-controlled additions to ?-silyloxy ketones. J Am Chem Soc 133:7969-76
Valenta, Petr; Carroll, Patrick J; Walsh, Patrick J (2010) Stereoselective synthesis of ?-hydroxy enamines, aminocyclopropanes, and 1,3-amino alcohols via asymmetric catalysis. J Am Chem Soc 132:14179-90
Stanton, Gretchen R; Johnson, Corinne N; Walsh, Patrick J (2010) Overriding Felkin control: a general method for highly diastereoselective chelation-controlled additions to alpha-silyloxy aldehydes. J Am Chem Soc 132:4399-408
Kim, Hun Young; Salvi, Luca; Carroll, Patrick J et al. (2010) One-pot catalytic enantio- and diastereoselective syntheses of anti-, syn-cis-disubstituted, and syn-vinyl cyclopropyl alcohols. J Am Chem Soc 132:402-12

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