Phase-transfer-catalyzed asymmetric acylimidazole alkylation.
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.
Andrus
Merritt B
MB
Department of Chemistry and Biochemistry, Brigham Young University, C100 BNSN, Provo, UT 84602, USA. mbandrus@chem.byu.edu
Christiansen
Michael A
MA
Hicken
Erik J
EJ
Gainer
Morgan J
MJ
Bedke
D Karl
DK
Harper
Kaid C
KC
Mikkelson
Shawn R
SR
Dodson
Daniel S
DS
Harris
David T
DT
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
D004952:Esters; D007093:Imidazoles; C029899:imidazole; D001554:Benzene