Highly Enantioselective Catalytic Phenylation of Ketones with a Constrained Geometry Titanium Catalyst
Celina García and Patrick J. Walsh*
*Roy and Diana Vagelos Laboratories, Department of Chemistry, University of
Pennsylvania, Philadelphia, Pennsylvania 19104-6323, Email: pwalsh
sas.upenn.edu
C. Garcia, P. J. Walsh, Org. Lett., 2003, 5, 3641-3644.
DOI: 10.1021/ol0352963
Abstract
The asymmetric addition of phenyl groups from diphenylzinc to ketones gives good to excellent enantioselectivity with a range of substrates, using a catalyst generated from a dihydroxy bis(sulfonamide) ligand and titanium tetraisopropoxide.
see article for more examples
Details
The document reports on the highly enantioselective catalytic phenylation of ketones using a constrained geometry titanium catalyst. Researchers Celina García and Patrick J. Walsh from the University of Pennsylvania developed a catalyst from a dihydroxy bis-(sulfonamide) ligand and titanium tetraisopropoxide, achieving good to excellent enantioselectivities across various substrates. The study addresses the challenge of asymmetric addition reactions to ketones, which are less prone to coordinate with Lewis acids compared to aldehydes. The optimized reaction conditions involved using 10 mol% of the ligand, 0.6 equivalents of titanium tetraisopropoxide, and 1.6 equivalents of diphenylzinc in toluene/hexanes at room temperature, yielding high enantioselectivity and product yield. The catalyst was effective with a range of ketone substrates, including acetophenone derivatives and α,β-unsaturated enones, producing tertiary alcohols with chiral quaternary centers. The study also explored the phenylation of α-halo ketones, leading to the formation of chiral epoxides. This method represents a significant improvement over previous methods, offering high yields and enantioselectivities without the need for methanol additives. Future research will focus on expanding the scope of reactions and understanding the reaction mechanism. The work was supported by the National Institutes of Health.
A Green Chemistry Approach to a More Efficient Asymmetric Catalyst: Solvent-Free and Highly Concentrated Alkyl Additions to Ketones
S.-J. Jeon, H. Li, P. J. Walsh, J. Am. Chem. Soc., 2005, 127, 16416-16425.
Key Words
ID: J54-Y2003-950
