On the origin of the stereoselectivity in organocatalysed reactions with trimethylsilyl-protected diarylprolinol
2008 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 14, no 1, 122-127 p.Article in journal (Refereed) Published
The origin of the enantioselectivity in the TMS-protected (TMS=trimethylsilyl) prolinol-catalysed alpha-heteroatom functionalisation of aldehydes has been investigated by using density functional theory calculations. Eight different reaction paths have been considered which are based on four different conformers of the TMS-protected prolinol-enamine intermediate. Optimisation of the enamine structures gave two intermediates with nearly the same energy. These intermediates both have an E configuration at the C==C bond and the double bond is positioned anti or syn, relative to the 2-substituent in the pyrrolidine ring. For the four intermediates, the chiral TMS-protected-diaryl substituent effectively shields one of the faces of the reacting C==C bond in the enamine intermediate. A number of transition states have been calculated for the enantioselective fluorination by N-fluorobenzenesulfonimide (NFSI) and based on the transition-state energies it has been found that the enantioselectivity depends on the orientation of the C==C bond, being anti or syn, relative to the 2-substituent on the pyrrolidine ring, rather than the approach of the electrophilic fluorine to the face of the reacting carbon atom in the enamine which is less shielded relative to the face with the highest shielding. The calculated enantiomeric excess of 96 % ee (ee=enantiomeric excess) for the fluorination reaction corresponds well with the experimentally found enantiomeric excess-97 % ee. The transition state for the alpha-amination reaction with the same type of intermediate has also been calculated by using diethyl azodicarboxylate as the amination reagent. The implication of the intermediate structures on the stereoselection of alpha-functionalisation of aldehydes is discussed.
Place, publisher, year, edition, pages
2008. Vol. 14, no 1, 122-127 p.
density functional theory, enamine, enantioselection, mechanism, organocatalysis
IdentifiersURN: urn:nbn:se:uu:diva-121902DOI: 10.1002/chem.200701244ISI: 000252538500009PubMedID: 17918758OAI: oai:DiVA.org:uu-121902DiVA: diva2:306913