Dedicated to Professor Henri Kagan on the occasion of his 80th birthdayThe structures of iminium salts formed from diarylprolinol or imidazolidinone derivatives and a,bunsaturated aldehydes have been studied by X-ray powder diffraction ( Fig. 1), single-crystal X-ray analyses (Table 1), NMR spectroscopy (Tables 2 and 3, Figs. 2 -7), and DFT calculations (Helv. Chim. Acta 2009Acta , 92, 1, 1225Acta , 2010 Angew. Chem., Int. Ed. 2009, 48, 3065). Almost all iminium salts of this type exist in solution as diastereoisomeric mixtures with (E)-and (Z)-configured þ N¼C bond geometries. In this study, (E)/(Z) ratios ranging from 88 : 12 up to 98 : 2 (Tables 2 and 3) and (E)/(Z) interconversions (Figs. 2 -7) were observed. Furthermore, the relative rates, at which the (E)-and (Z)-isomers are formed from ammonium salts and a,b-unsaturated aldehydes, were found to differ from the (E)/(Z) equilibrium ratio in at least two cases (Figs. 4 and 5, a, and Fig. 6, a); more (Z)-isomer is formed kinetically than corresponding to its equilibrium fraction. Given that the enantiomeric product ratios observed in reactions mediated by organocatalysts of this type are often ! 99 : 1, the (E)-iminium-ion Helvetica Chimica Acta -Vol. 93 (2010) intermediates are proposed to react with nucleophiles faster than the (Z)-isomers (Scheme 5 and Fig. 8).Possible reasons for the higher reactivity of (E)-iminium ions (Figs. 8 and 9) and for the kinetic preference of (Z)-iminium-ion formation are discussed (Scheme 4). The results of related density functional theory (DFT) calculations are also reported (Figs. 10 -13 and Table 4).1. Introduction. -Since the renaissance of organocatalysis 6 ) in 2000 [3], this field has undergone an explosive development 7 ). Of the various types of organocatalysts, compounds with a sec-amino group (proline and its derivatives, including diarylprolinol ethers [5], and amino acid (mostly phenylalanine)-derived imidazolidinones [3b]) have experienced the widest use. They activate a-carbonyl positions for electrophilic attack 8 ) through enamines and b-carbonyl positions for nucleophilic attack through iminium ions, thus opening the door to enantioselectively catalyzed versions of the most important classical synthetic organic reactions 9 ). Entire sequences of such reactions can be performed with one organocatalyst, or with two different species, culminating in the formation of four and more stereogenic centers via so-called domino or cascade reactions [8]. However, much of the mechanistic intricacies of organocatalytic transformations remain unexplored; a casualty of the excitement that the synthetic competence of this class of small molecules has generated. Often reasonable mechanistic models are proposed that are based solely on the stereochemical outcome of the transformation in question.On closer inspection, aspects of many commonly accepted mechanistic models were identified that led to the proposal of possible alternatives. Thus, in proline catalysis, the role of oxazolidinones may not just be part of a parasiti...
