Stereochemical Models for Discussing Additions to α,β‐Unsaturated Aldehydes Organocatalyzed by Diarylprolinol or Imidazolidinone Derivatives – Is There an ‘(E)/(Z)‐Dilemma’?

Abstract

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...

IR and NMR Spectral Studies of Some 4-(6-methoxy-2-naphthyl)-5,6-dihydro-6-(Substituted Phenyl)-⁴<i>H</i>-1,3-Oxazine-2-Amines: Assessment of Substituent

“…From the infrared spectral frequencies E s-cis and s-trans conformers of styrenes [2], polyenes [3], chalcones [4], unsaturated aldehydes [5], acid chlorides [6], unsaturated esters [7], gauche and anti-form acyl halides and its esters [8]. Nuclear magnetic resonance spectral chemical shifts was used for prediction of the spatial arrangement of protons such as cis and trans of organic stereo chemical compounds [9].…”

Organocatalyzed Transformations of á, â‐Unsaturated Carbonyl Compounds through Iminium Ion Intermediates

“…Of particular note among these are the diarylprolinol ethers [10]. Significantly less work has been carried out to understand the reactivity of this class of catalyst, where the mode of asymmetric induction appears significantly more complex than that delineated for imidazolidinones [6].A substantial amount of data has been published to compare the relative reactivity of a number of different catalyst structures (including imidazolidinones and diarylprolinol ethers) for both cycloaddition and conjugate addition reactions [11]. It has also been shown that both proton affinity of the parent amine and LUMO energy level of the corresponding iminium ion can be used as useful ground state predictors of relative reactivity [12].…”

“…Of particular note among these are the diarylprolinol ethers [10]. Significantly less work has been carried out to understand the reactivity of this class of catalyst, where the mode of asymmetric induction appears significantly more complex than that delineated for imidazolidinones [6].…”

“…Within the imidazolidinone series, two principal structures have been reported: imidazolidinone (6), which has been used in the acceleration of cycloadditions and closed transition state conjugate addition reactions, and the pivaldehyde-derived imidazolidinone (7), which has been used for conjugate addition processes and intramolecular cycloadditions [4,5].…”

“…It has been shown that steric interaction between the geminal dimethyl group of the catalyst and the C-H α-to the aldehyde disfavors 9 and that at equilibrium the ratio of 8/9 is 98 : 2 [6].…”