This proposal aims to develop regio- and enantioselective methods for the preparation of chiral, branched allylboronates and allylsilanes.
Specific aims i nclude: 1) the identification/development of chiral transition metal catalysts that promote highly regio- and enantioselective allylic borylation and silylation;2) development of a direct, broadly applicable method for synthesis of enantioenriched, branched allyboronates by asymmetric allylic substitution;3) fundamental understanding of reaction mechanisms and stereochemical outcomes when nucleophiles other than carbon, nitrogen, and oxygen are employed in asymmetric allylic substitutions;and 4) extension of this allylic substitution methodology to include silicon nucleophiles for the preparation of enantioenriched, branched allylsilanes. Realization of the specific aims of the proposal has the potential for much broader relevance. Access to a variety of chiral, branched allylboronates and allylsilanes from a single method or closely related methods will be of value due to the broad synthetic application of these small molecules, chiral building blocks. Furthermore, successful development of allylic borylation and silylation methods will represent a fundamental shift in terms nucleophiles commonly employed in asymmetric allylic substitutions. Greater understanding of mechanistic aspects is likely to lead to improvements in experimental design and may provide insights into expanding the availability of additional chiral, allylic substitution products.

Public Health Relevance

Development of methods for the synthesis of small molecule, chiral building blocks continues to be of fundamental importance for the preparation of biologically relevant compounds. In recent years the ability to access chiral drug candidate molecules in enantioenriched and/or enantiopure form has become increasingly important. Thus, methods to access enantioenriched chiral building blocks, such as branched allylboronates and allylsilanes, used in the synthesis of biologically active compounds has been and will continue to be relevant to public health.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F04A-T (20))
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Fabian, Miles
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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Liao, Xuebin; Stanley, Levi M; Hartwig, John F (2011) Enantioselective total syntheses of (-)-taiwaniaquinone H and (-)-taiwaniaquinol B by iridium-catalyzed borylation and palladium-catalyzed asymmetric ?-arylation. J Am Chem Soc 133:2088-91
Stanley, Levi M; Bai, Chen; Ueda, Mitsuhiro et al. (2010) Iridium-catalyzed kinetic asymmetric transformations of racemic allylic benzoates. J Am Chem Soc 132:8918-20
Hartwig, John F; Stanley, Levi M (2010) Mechanistically driven development of iridium catalysts for asymmetric allylic substitution. Acc Chem Res 43:1461-75
Pouy, Mark J; Stanley, Levi M; Hartwig, John F (2009) Enantioselective, iridium-catalyzed monoallylation of ammonia. J Am Chem Soc 131:11312-3
Stanley, Levi M; Hartwig, John F (2009) Iridium-catalyzed regio- and enantioselective N-allylation of indoles. Angew Chem Int Ed Engl 48:7841-4
Stanley, Levi M; Hartwig, John F (2009) Regio- and enantioselective N-allylations of imidazole, benzimidazole, and purine heterocycles catalyzed by single-component metallacyclic iridium complexes. J Am Chem Soc 131:8971-83