Dynamic kinetic protonation

The enantioselective synthesis of an allenic ester using chiral proton sources was performed by dynamic kinetic protonation of racemic allenylsamarium(III) species 237 and 238, which were derived from propargylic phosphate 236 by the metalation (Scheme 4.61) [97]. Protonation with (R,R)-(+)-hydrobcnzoin and R-(-)-pantolactone provided an allenic ester 239 with high enantiomeric purity. The selective protonation with (R,R)-(+)-hydrobenzoin giving R-(-)-allcnic ester 239 is in agreement with the... 

Table 9.61 Dynamic kinetic protonation of chiral racemic allenylsamarium intermediates.

The first example of asymmetric synthesis of allenic esters by a samarium(ii)-mediated reduction of propargylic compounds through dynamic kinetic protonation performed in the presence of a palladium catalyst was reported by Mikami and colleagues. Various chiral proton sources were involved and furnished enantio-enriched allenic esters, as shown in Scheme 2.47. 

The allenyl carboxylate 35 was obtained in an enantiomerically enriched form by the palladium-catalyzed reduction of the racemic phosphate 34 using a chiral proton source [53]. The two enantiomers of the (allenyl)samarium(III) intermediate are in rapid equilibrium and thus dynamic kinetic resolution was achieved for the asymmetric preparation of (i )-35 (Scheme 3.18). 

In this section, dynamic kinetic resolution of substrates having a proton with low pKa is discussed. Racemization occurs by performing the DKR in the presence of a weak base. Enzyme- and base-catalyzed DKRs are categorized, according to the nature of the substrates, as being thioesters, -activated esters, oxazolones, hydan-toins or acyloins. 

The 1977 review of Martynov et al. [12] discusses existing mechanisms of ESPT, excited-state intramolecular proton transfer (ESIPT) and excited-state double-proton transfer (ESDPT). Various models that have been proposed to account for the kinetics of proton-transfer reactions in general. They include that of association-proton-transfer-dissociation model of Eigen [13], Marcus adaptation of electron-transfer theory [14], and the intersecting state model by Varandas and Formosinho [15,16], Gutman and Nachliel s [17] review in 1990 offers a framework of general conclusions about the mechanism and dynamics of proton-transfer processes. 

The dynamics of proton binding to the extra cellular and the cytoplasmic surfaces of the purple membranes were measured by the pH jump methods [125], The purple membranes selectively labeled by fluorescein Lys-129 of bacteri-orhodopsin were pulsed by protons released in the aqueous bulk from excited pyranine and the reaction of the protons with the indicators was measured. Kinetic analysis of the data implied that the two faces of the membrane differ in then-buffer capacities and in their rates of interaction with bulk protons. The extracellular surfaces of the purple membrane contains one anionic proton binding site per protein molecule with pA" 5.1. This site is within a Coulomb cage radius from Lys-129. The cytoplasmic surface of the purple membrane bears four to five pro-tonable moieties that, due to close proximity, function as a common proton binding site. The reaction of the proton with this cluster is at a very fast rate (3 X 1010 M-1 sec ). The proximity between the elements is sufficiently high that even in 100 mM NaCl, they still function as a cluster. Extraction of the chromophore retinal from the protein has a marked effect on the carboxylates of the cytoplasmic surface, and two to three of them assume positions that almost bar their reaction with bulk protons. Quantitative evaluation of the dynamics of proton transfer from photoactivated bacteriorhodopsin to the bulk has been done by using numerical... 

Among asymmetric version of barium-catalyzed aldol reactions, the direct aldol reaction of y3,y-unsaturated esters with aldehydes is promising due to the DYKAT (dynamic kinetic asymmetric transformation). Shibasaki and coworkers (147) established an optimized catalyst system for the DYKAT involving aldol/retro-aldol reaction, that a Ba(0-iPr)2/BIN0L mixture gave excellent enan-tioinduction and conversion (Scheme 32). a-Alkylidene-y3-hydroxy esters were obtained under proton-transfer conditions via DYKAT in 87-99% ee. 

Considering that the a-proton-exchange of racemic azlactones occurred rapidly in the presence of a tertiary amine base. Song and coworkers demonstrated enan-tioselective synthesis of a-deuterated a-amino acids via dynamic kinetic resolution (DKR) of azlactones with EtOD using cinchona-derived dimeric squaramide catalyst 33 (Scheme 10.34) [112]. The authors noted that by increasing the amount of EtOD, the level of deuterium incorporation increased, whereas the enantioselectivity decreased. By using 50 equivalents of EtOD, the products were obtained with... 

Supplemental use of racemose enzymes The main disadvantage of kinetic racemate resolution is the limitation of yield to 50%, unless the undesired isomer is racemized and the resolution repeated. An elegant alternative to this tedious, terative procedure is the dynamic, kinetic racemate resolution (Figure 12.6), which combines a fast racemization equilibrium (5)-A (,R)-A with an enantioselective transformation in order to accomplish the dera-cemization process. In addition to the chemical methods (such as thermal-, acid/base-, deprotonation/protonation processes) enzyme-catalyzed methods also find application for this racemization process. The use of racemases (EC. 5.1) has recently been reviewed . 

The study of prototropic tautomerization is intimately related to the study of proton transfer reactions. The study of the dynamics of proton transfer is as old as the study of reaction kinetics itself Indeed, the first reactions studied, that is, the inversion of sugar by Wilhehny in 1850 [65], involves a proton transfer as the elementary step in the reaction. In the first studies on the dynamics of tautomerization, primarily keto-enol tautomerization in acetone-like compounds were studied, which is a slow process involving a number of reaction steps of which the acid catalyzed keto-enol conversion was taken as the rate determining one [66]. In the past century, since 1910, nearly 2000 papers have been published on the kinetics of tautomerization, and in the first 60 years most of those were devoted to the ground-state reactions of the keto-enol type involving a C atom. Until the mid-1950s, only a handful of papers can be found this was obviously due to experimental hmitations. Two things are needed a method to start the reaction, and a method to follow it. In Dawson s experiments [66], the rate could be influenced by the amount of acid present, and the reaction could be followed because the enol produced... 

Studies of kinetics and dynamics in proton transfer systems frequently require the knowledge of short-Hved intermediates and transition states. These parameters are often difficult to derive experimentally and this is why ab initio and DFT methods have emerged as a powerfiil supplementary tool for obtaining details of a tautomerization process that are not available from experiments and for providing feedback on models used to interpret experimental data [80]. 

Anne, A., Hapiot, P., Moiroux, J., Neta, P., and Saveant, J.-M., Dynamics of proton transfer from cation radicals. Kinetic and thermodynamic acidities of cation radicals of NADH analogs, /. Am. Chem. Soc., 114, 4694, 1992. 

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