title: Phase-transfer-catalyzed asymmetric acylimidazole alkylation.
abstract: 2-Acylimidazoles are alkylated under phase-transfer conditions with cinchonidinium catalysts at -40 degrees C with allyl and benzyl electrophiles in high yield with excellent enantioselectivity (79 to >99% ee). The acylimidazole substrates are made in three steps from bromoacetic acid via the N-acylmorpholine adduct. The catalyst is made in high purity allowing for S-product formation (6-20 h) under mild conditions, consistent with an ion-pair mechanism. The products are readily converted to useful ester products using methyltriflate and sodium methoxide, via a dimethylacylimidazolium intermediate without racemization. The process is efficient, direct, and amenable to other electrophiles and transformations that proceed through an enolate intermediate.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, C100 BNSN, Provo, UT 84602, USA. mbandrus@chem.byu.edu
authors.forename: Merritt B
authors.initials: MB
authors.lastname: Andrus
authors.forename: Michael A
authors.initials: MA
authors.lastname: Christiansen
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Hicken
authors.forename: Morgan J
authors.initials: MJ
authors.lastname: Gainer
authors.forename: D Karl
authors.initials: DK
authors.lastname: Bedke
authors.forename: Kaid C
authors.initials: KC
authors.lastname: Harper
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Mikkelson
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Dodson
authors.forename: David T
authors.initials: DT
authors.lastname: Harris
mesh_terms: D000215:Acylation; D000478:Alkylation; D001554:Benzene / Q000737:chemistry; D002384:Catalysis; D004583:Electrons; D004952:Esters / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D044367:Phase Transition; D013237:Stereoisomerism
chemical_list: D004952:Esters; D007093:Imidazoles; C029899:imidazole; D001554:Benzene