title: A green chemistry approach to a more efficient asymmetric catalyst: solvent-free and highly concentrated alkyl additions to ketones.
abstract: There is a great demand for development of catalyst systems that are not only efficient and highly enantioselective but are also environmentally benign. Herein we report investigations into the catalytic asymmetric addition of alkyl and functionalized alkyl groups to ketones under highly concentrated and solvent-free conditions. In comparison with standard reaction conditions employing toluene and hexanes, the solvent-free and highly concentrated conditions permit reduction in catalyst loading by a factor of 2- to 40-fold. These new conditions are general and applicable to a variety of ketones and dialkylzinc reagents to provide diverse tertiary alcohols with high enantioselectivities. Using cyclic conjugated enones, we have performed a tandem asymmetric addition/diastereoselective epoxidation using the solvent-free addition conditions followed by introduction of a 5.5 M decane solution of tert-butyl hydroperoxide (TBHP) to generate epoxy alcohols. This one-pot procedure allows access to syn epoxy alcohols with three contiguous stereocenters with excellent enantio- and diastereoselectivities and high yields. Both the solvent-free asymmetric additions and asymmetric addition/diastereoselective epoxidation reactions have been conducted on larger scale (5 g substrate) with 0.5 mol % catalyst loadings. In these procedures, enantioselectivities equal to or better than 92% were obtained with isolated yields of 90%. The solvent-free and highly concentrated conditions are a significant improvement over previous solvent-based protocols. Further, this chemistry represents a rare example of a catalytic asymmetric reaction that is highly enantioselective under more environmentally friendly solvent-free conditions.
authors.affiliation: Department of Chemistry, P. Roy and Diana T. Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Walsh
mesh_terms: D000478:Alkylation; D002384:Catalysis; D004777:Environment; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D007659:Ketones; D009942:Organometallic Compounds; D012997:Solvents; C454811:diethylzinc