The broad, long-term objectives of this proposal are to develop new synthetic methods that enable the preparation of important intermediates for organic and medicinal chemistry. Our methods make possible, for the first time, the large-scale synthesis of enantioenriched diarylmethanols from aryl bromides. This method will be applied to the synthesis of enantiomerically enriched heterocycles bearing important pharmacophores, such as furans and pyridines. We have also developed several new routes to pyranones, furanosidic aldehydes, furans, and pyrroles. These medicinally important heterocycles can be prepared with high enantioselectivities using our methods. We have developed one-pot synthesis of a-hydroxy ketones, allylic alcohols, and substituted cyclopropanes from a versatile 1-alkenyl-1,1-bimetallic intermediate. These methods will be useful in complex molecule synthesis.
The Specific Aims of this proposal are: I. Development of Direct Methods for Conversion of Aryl, Vinyl, and Alkyl Bromides to Enantioenriched Alcohols. II. Introduction of New Methods For Heterocycle Syntheses. III: Development of 1-Alkenyl-1,1-Bimetallic Reagents for Complex Molecule Synthesis. This project presents new methods to synthesize important chiral building blocks that were not easily accessible, but find utility in health-related applications, particularly in the synthesis of enantioenriched pharmaceutical agents. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Synthetic and Biological Chemistry A Study Section (SBCA)
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Schwab, John M
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University of Pennsylvania
Schools of Arts and Sciences
United States
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Stanton, Gretchen R; Kauffman, Meara C; Walsh, Patrick J (2012) Diastereoselective chelation-controlled additions to ?-silyloxy aldehydes. Org Lett 14:3368-71
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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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