Phosphoric Acid Catalyzed Enantioselective Transfer Hydrogenationof Imines: A Density Functional Theory Study of Reaction Mechanismand the Origins of Enantioselectivity
2008 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 14, 8562-8571 p.Article in journal (Refereed) Published
The phosphoric acid catalyzedreaction of 1,4-dihydropyridineswith N-arylimines has been investigatedby using density functional theory.We first considered the reaction of acetophenonePMP-imine (PMP=p-methoxyphenyl)with the dimethylHantzsch ester catalyzed by diphenylphosphate. Our study showed that, inagreement with what has previouslybeen postulated for other reactions, diphenylphosphate acts as a Lewis base/Brønsted acid bifunctional catalyst inthis transformation, simultaneously activatingboth reaction partners. The calculationsalso showed that the hydridetransfer transition states for the E andZ isomers of the iminium ion havecomparable energies. This observationturned out to be crucial to the understandingof the enantioselectivity of theprocess. Our results indicate that whenusing a chiral 3,3’-disubstituted biarylphosphoric acid, hydride transfer to theRe face of the (Z)-iminium is energeticallymore favorable and is responsiblefor the enantioselectivity, whereas thecorresponding transition states for nucleophilicattack on the two faces ofthe (E)-iminium are virtually degenerate.Moreover, model calculations predictthe reversal in enantioselectivityobserved in the hydrogenation of 2-arylquinolines,which during the catalyticcycle are converted into (E)-iminiumions that lack the flexibility of thosederived from acyclic N-arylimines. Inthis respect, the conformational rigidityof the dihydroquinolinium cation imposesan unfavorable binding geometryon the transition state for hydridetransfer on the Re face and is thereforeresponsible for the high enantioselectivity.
Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlag GmbH&Co. KGaA , 2008. Vol. 14, 8562-8571 p.
ensity functional calculations; hydrogenation; imines; organocatalysis; pyridines
IdentifiersURN: urn:nbn:se:kth:diva-11611DOI: 10.1002/chem.200800890ISI: 000260035900018ScopusID: 2-s2.0-53849122697OAI: oai:DiVA.org:kth-11611DiVA: diva2:278322
QC 201007192009-11-252009-11-252010-12-06Bibliographically approved