Proton transfer enantioselective

The detailed mechanism of this enantioselective transformation remains under investigation.178 It is known that the acidic carboxylic group is crucial, and the cyclization is believed to occur via the enamine derived from the catalyst and the exocyclic ketone. A computational study suggested that the proton transfer occurs through a TS very similar to that described for the proline-catalyzed aldol reaction (see page 132).179... 

The optically active Schiff bases containing intramolecular hydrogen bonds are of major interest because of their use as ligands for complexes employed as catalysts in enantioselective reactions or model compounds in studies of enzymatic reactions. In the studies of intramolecularly hydrogen bonded Schiff bases, the NMR spectroscopy is widely used and allows detection of the presence of proton transfer equilibrium and determination of the mole fraction of tautomers [21]. Literature gives a few names of tautomers in equilibrium. The OH-tautomer has been also known as OH-, enol- or imine-form, while NH tautomer as NH-, keto-, enamine-, or proton-transferred form. More detail information concerning the application of NMR spectroscopy for investigation of proton transfer equilibrium in Schiff bases is presented in reviews.42-44... 

The proton transfer from multiply charged [cytochrome c] " (n = 7-9) to (/ )- and (5)-2-butylamine show a significant enantioselectivity." " Ions [cytochrome n = l-9) were produced by ESI and introduced into the analyzer cell of a FT-ICR containing an alkylamine, i.e., (/ )- and (5)-2-butyIamine, 1-propylamine, or tert-butylamine. Rate constants for the proton transfer are listed in Table 18. 

The favourable effect of lithium bromide on facial enantioselective protonation of methyl tetralone enolate by a-sulfinyl alcohols has been attributed to coordination of lithium to both enolate and sulfinyl alcohol followed by competition between diastere-omeric paths involving intramolecular proton transfer the proposed transition-state model is supported by results of PM3 semiempirical calculations. ... 

Mechanistically, the Brpnsted acid-catalyzed cascade hydrogenation of quinolines presumably proceeds via the formation of quinolinium ion 56 and subsequent 1,4-hydride addition (step 1) to afford enamine 57. Protonation (step 2) of the latter (57) followed by 1,2-hydride addition (step 3) to the intermediate iminium ion 58 yields tetrahydroquinolines 59 (Scheme 21). In the case of 2-substituted precursors enantioselectivity is induced by an asymmetric hydride transfer (step 3), whereas for 3-substituted ones asymmetric induction is achieved by an enantioselective proton transfer (step 2). 

Propynyl bromides can be enantioselectively converted to chiral allenes by stoichiometric conversion into a propynylchromium(III) complex followed by stereoselective proton transfer from a chiral auxiliary, e.g., (-)-borneol or (-)-menthol120, l2 . Formally, substitution of bromide takes place. 

When the alkylation was performed with ethyl allyl carbonate as the precursor of the it-allyl intermediate, only 32% ee was obtained, indicative of a subtle proton-transfer process involved in the catalytic process such as in Scheme 8E.39. The chiral rhodium catalyst was shown to be the primary source of the asymmetric induction because the same reaction in the absence of the rhodium catalyst generated a racemic product in 91% yield. It is interesting that the use of only half an equivalent of the chiral ligand together with half an equivalent of achiral ligand (dppb) with respect to [Pd + Rh] was sufficient to give a high enantioselectivity (93% ee). 

An NMR kinetic study of a phosphine-catalysed aza-Baylis-Hillman reaction of but-3-enone with arylidene-tosylamides showed rate-limiting proton transfer in the absence of added protic species, but no autocatalysis.175 Brpnsted acids accelerate the elimination step. Study of the effects of BINOL-phosphinoyl catalysts sheds light not only on the potential for enantioselection with such bifunctional catalysis, but also on their scope for catalysing racemization. 

Quantum chemical DFT calculations at the B3LYP/6-31G(d) level have been used to study the enantioselective lithiation/deprotonation of O -alkyl and O-alk-2-enyl carbamates in the presence of (—)-sparteine and (—)-(f )-isosparteine.7 Complete geometry optimization of the precomplexes consisting of the carbamate, the chiral ligand, and the base (/-PrLi), for the transition states of the proton-transfer reaction, and for the resulting lithio carbamates have been performed in order to quantify activation barriers and reaction energies. 

The general reaction mechanism of the Michael reaction is given below (Scheme 4). First, deprotonation of the Michael donor occurs to form a reactive nucleophile (A, C). This adds enantioselectively to the electron-deficient olefin under the action of the chiral catalyst. In the final step, proton transfer to the developed enolate (B, D) occurs from either a Michael donor or the conjugate acid of a catalyst or a base, affording the desired Michael adduct. It is noteworthy that the large difference of stability between the two enolate anions (A/B, C/D) is the driving force for the completion of the catalytic cycle. 

The enantioselective synthesis of (-)-sedacryptine, a piperidine alkaloid, has been achieved via the double intramolecular conjugate addition of a carbamate group onto a vinyl sulfone and then an enone (Scheme 30). The first conjugate addition of 108 proceeded in a. syn-1,3 fashion. The successive cyclization of the resulting carbamate anion 110, which was formed from carbanion 109 via proton transfer, gave a mixture of stereoisomeric products 111 and 112. Both of these isomers were converted into the target natural product.76... 

Liang G, Trauner D (2004) Enantioselective Nazarov reactions through catalytic asymmetric proton transfer. J Am Chem Soc 126 9544—9545 Liu B, Feng X, Chen F, Zhang G, Cui X, Jiang Y (2001) Synlett 2001 1551 Liu H, Cun LF, Mi AQ, Jiang YZ, Gong LZ (2006) Enantioselective direct aza hetero-Diels-Alder reaction catalyzed by chiral Brpnsted acids. Org Lett 8 6023-6026... 

Eaton s base also has stimulated use of an enantiopure alkylmagnesium amide for enantioselective deprotonation of a set of 4-substituted cyclohexanones (equation 36) further work in this area can be expected. Einally, efficient ortho-magnesiation of A-phenylsulfonylpyrrole has been achieved with an excess of (PrMgCl and a catalytic amount (5mol%) of (Pr2NH to serve as a proton transfer agent subsequent reaction with a range of electrophiles afforded decent yields of products (equation 37). ... 

A preliminary approach to understand the mechanism of the enantioselective protonation and the role of lithium bromide, based on TSs containing one hthium atom, failed to explain the selectivity enhancement by hthium bromide, and the calculated energies of the TSs did not account for the experimentally observed selectivity. Asensio, Domingo and coworkers studied the molecular process associated with the proton transfer at the semiempirical PM3 level . Based on hterature data , they defined the structure of a mixed dimer enolate 234 consisting of a four-membered ring where the bromide anion and the oxygen atom of the enolate were connected by two hthium cations. These bridging... 

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