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Structures of the Reactive Intermediates in Organocatalysis with Diarylprolinol Ethers
Author(s) -
Grošelj Uroš,
Seebach Dieter,
Badine D. Michael,
Schweizer W. Bernd,
Beck Albert K.,
Krossing Ingo,
Klose Petra,
Hayashi Yujiro,
Uchimaru Tadafumi
Publication year - 2009
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200900179
Subject(s) - iminium , chemistry , organocatalysis , pyrrolidine , crystal structure , medicinal chemistry , stereochemistry , enamine , ion , crystallography , organic chemistry , catalysis , enantioselective synthesis
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, PhCH 2 CHO, t BuCH 2 CHO, PhCH=CHCHO, 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 BF 4 , PF 6 , SbF 6 , and the weakly coordinating Al[OC(CF 3 ) 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 CDCl 3 , (D 6 )DMSO, (D 6 )acetone, or CD 3 OD; Table 1 ), the major isomers 4 of the iminium salts have ( E )‐configuration of the exocyclic NC(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‐CC‐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 , CF 3 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.