Structures of the reactive intermediates in organocatalysis with diarylprolinol ethers

Uroš Grošelj, Dieter Seebach, D. Michael Badine, W. Bernd Schweizer, Albert K. Beck, Ingo Krossing, Petra Klose, Yujiro Hayashi, Tadafumi Uchimaru

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Abstract

Structures of the reactive intermediates (enamines and iminium ions) of organocatalysis with diarylprolinol derivatives have been determined. To this end, diarylprolinol methyl and silyl ethers, 1, and aldehydes, Ph-CH 2-CHO, tBu-CH2-CHO, Ph-CH=CH-CHO, are condensed to the corresponding enamines, A and 3 (Scheme 2), and cinnamoylidene iminium salts, B and 4 (Scheme 3). These are isolated and fully characterized by melting/decomposition points, [α]D, elemental analysis, IR and NMR spectroscopy, and high-resolution mass spectrometry (HR-MS). Salts with BF4, PF6, SbF6, and the weakly coordinating Al[OC(CF3)3]4 anion were prepared. X-Ray crystal structures of an enamine and of six iminium salts have been obtained and are described herein (Figs. 2 and 4-8, and Tables 2 and 7) and in a previous preliminary communication (Helv. Chim. Acta 2008, 91, 1999). According to the NMR spectra (in CDCl3, (D6)DMSO, (D6)acetone, or CD3OD; Table 1), the major isomers 4 of the iminium salts have (E)-configuration of the exocyclic N=C(1′) bond, but there are up to 11% of the (Z)-isomer present in these solutions (Fig. 1). In all crystal structures, the iminium ions have (E)-configuration, and the conformation around the exocyclic N-C-C-O bond is synclinal-exo (cf. C and L), with one of the phenyl groups over the pyrrolidine ring, and the RO group over the π-system. One of the meta-substituents (Me in 4b, CF3 in 4c and 4e) on a 3,5-disubstituted phenyl group is also located in the space above the π-system. DFT Calculations at various levels of theory (Tables 3-6) confirm that the experimentally determined structures (cf. Fig. 10) are by far (up to 8.3 kcal/mol) the most stable ones. Implications of the results with respect to the mechanism of organocatalysis by diarylprolinol derivatives are discussed.

Original languageEnglish
Pages (from-to)1225-1259
Number of pages35
JournalHelvetica Chimica Acta
Volume92
Issue number7
DOIs
Publication statusPublished - 2009 Jul 1
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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    Grošelj, U., Seebach, D., Badine, D. M., Schweizer, W. B., Beck, A. K., Krossing, I., Klose, P., Hayashi, Y., & Uchimaru, T. (2009). Structures of the reactive intermediates in organocatalysis with diarylprolinol ethers. Helvetica Chimica Acta, 92(7), 1225-1259. https://doi.org/10.1002/hlca.200900179