Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate
Alistair J M Farley1, Christopher Sandford1, Darren J Dixon1
1The Department of Chemistry, Chemistry Research Laboratory, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, U.K.
Abstract:
The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated α-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Brønsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a central thiourea hydrogen-bond donor facilitate high enantiofacial selectivity in the protonation of the transient enolate intermediate. The reaction is broad in scope with respect to the alkyl thiol, the ester moiety, and the α-substituent of the α,β-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivities (up to 96% ee), and is amenable to decagram scale-up using catalyst loadings as low as 0.05 mol %.
More Related Videos
06:46Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
10:42Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Related Concept Videos
Conjugate Addition of Enolates: Michael Addition
Acid Halides to Esters: Alcoholysis
α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
