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.
ASJC Scopus subject areas
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry