Solution Phase, Solid State, and Theoretical Investigations on the MacMillan Imidazolidinone

Brazier, John B.; Evans, Gareth J. S.; Gibbs, Timothy J. K.; Coles, Simon J.; Hursthouse, M. B.; Platts, James Alexis; Tomkinson, Nicholas C. O.

doi:10.1021/ol802512y

Cited by 70 publications

(35 citation statements)

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“…Comparison of the values suggests that attack of HO À to (E)-and (Z)-iminium ions has approximately the same exothermicity 24 ). In the optimized geometries, the N-atoms have a small degree of pyramidalization in the direction of the large substituent at C(2) of the pyrrolidine ring, in agreement with all previously calculated [12] [15b] [16] [17b] [25] and measured [12] [15] [16] structures. To see whether a change in the pyramidalization direction could be detected by DFT calculations when we go from an a-heterosubstituted amine (for which there is ample evidence of virtual antiperiplanar (ap) arrangement of the lone-pair and the CÀX bond; see H in Fig.…”

Section: Kinetics Of the Formation Of Iminiumsupporting

confidence: 88%

“…An (E)/(Z)-Dilemma in Organocatalysis with Diarylprolinol and Imidazolidinone Derivatives? -The results described in the previous sections, which are supported by theory [12] [13] [15] [16] [17b] [25], must be considered strong evidences for the formation of both (E)-and (Z)-iminium ions in reactions between enals and the organocatalysts with secondary amino groups. Not only are the two diastereoisomers formed from their precursors, but they are in equilibrium with each other at ambient temperatures in various solvents.…”

Section: Kinetics Of the Formation Of Iminiumsupporting

confidence: 62%

“…Finally, the more electrophilic iminium ions derived from 5-benzylimidazolidinones 10 ) appear to exist as an equilibrating mixture of conformers around the exocyclic benzylic ethane bond, in which the conformer with the Ph group over the heterocyclic ring (and not, as commonly assumed, over the p-system) generally prevails (according to DFT, NMR, and X-ray investigations) (Eqn. 3)) [11] [15] [16]. Here, we…”

Section: Dedicated To Professor Henri Kagan On the Occasion Of His 80mentioning

confidence: 99%

“…Sect. 5) that the (E)/(Z)-geometry of the iminium ion derived from 5-benzyl-2,3-dimethyl-2-phenylimidazolidinone and cinnamaldehyde is determined by the antiperiplanarity of the lone pair at the N-atom and the leaving group H 2 O in the intermediate O-protonated a-amino alcohol derivative (see center of Scheme 4), we have to compare the various approach trajectories of the trigonal centers 16 ), that lead to these intermediates (Scheme 4, top and bottom). Of the two diastereotopic approaches of N(1) on the less sterically encumbered face (MeÀC(2)/ HÀC(5) vs. PhÀC(2)/PhCH 2 ÀC(5)) of the imidazolidinone to the Re-and Si-face of cinnamaldehyde, the Re-approach, leading to the (Z)-precursor, appears to be more favorable (cf.…”

Section: Kinetics Of the Formation Of Iminiummentioning

confidence: 99%

“…Activation barriers are low enough to observe interconversions down to temperatures of À 308. 16 ) For a topological rule for the coupling of trigonal centers, see [24].…”

Section: Kinetics Of the Formation Of Iminiummentioning

confidence: 99%

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

Seebàch

Gilmour

Grošelj

et al. 2010

Helvetica Chimica Acta

102

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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...

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Section: Kinetics Of the Formation Of Iminiumsupporting

confidence: 88%

Section: Kinetics Of the Formation Of Iminiumsupporting

confidence: 62%

Section: Dedicated To Professor Henri Kagan On the Occasion Of His 80mentioning

confidence: 99%

Section: Kinetics Of the Formation Of Iminiummentioning

confidence: 99%

“…Activation barriers are low enough to observe interconversions down to temperatures of À 308. 16 ) For a topological rule for the coupling of trigonal centers, see [24].…”

Section: Kinetics Of the Formation Of Iminiummentioning

confidence: 99%

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