Dynamic kinetically resolved

Racemic epichlorhydrin 32 can be dynamically kinetically resolved using a salen chromium complex 31. The enantiomeric excess of the product 33 is excellent at 97% and the yield 76%.24... 

The complete transformation of a racemic mixture into a single enantiomer is one of the challenging goals in asymmetric synthesis. We have developed metal-enzyme combinations for the dynamic kinetic resolution (DKR) of racemic primary amines. This procedure employs a heterogeneous palladium catalyst, Pd/A10(0H), as the racemization catalyst, Candida antarctica lipase B immobilized on acrylic resin (CAL-B) as the resolution catalyst and ethyl acetate or methoxymethylacetate as the acyl donor. Benzylic and aliphatic primary amines and one amino acid amide have been efficiently resolved with good yields (85—99 %) and high optical purities (97—99 %). The racemization catalyst was recyclable and could be reused for the DKR without activity loss at least 10 times. 

The integration of a catalyzed kinetic enantiomer resolution and concurrent racemization is known as a dynamic kinetic resolution (DKR). This asymmetric transformation can provide a theoretical 100% yield without any requirement for enantiomer separation. Enzymes have been used most commonly as the resolving catalysts and precious metals as the racemizing catalysts. Most examples involve racemic secondary alcohols, but an increasing number of chiral amine enzyme DKRs are being reported. Reetz, in 1996, first reported the DKR of rac-2-methylbenzylamine using Candida antarctica lipase B and vinyl acetate with palladium on carbon as the racemization catalyst [20]. The reaction was carried out at 50°C over 8 days to give the (S)-amide in 99% ee and 64% yield. Rather surpris-... 

An elegant way to avoid the low yields and the need for recycling half of the material in the case of kinetic resolutions is a dynamic kinetic resolution (DKR). The dynamic stands for the dynamic equilibrium between the two enantiomers that are kinetically resolved (Scheme 6.6A). This fast racemisation ensures that the enzyme is constantly confronted with an (almost) racemic substrate. At the end of the reaction an enantiopure compound is obtained in 100% yield from racemic starting material. Mathematical models describing this type of reaction have been published and applied to improve this important reaction [32, 33]. There are several examples, in which the reaction was performed in water (see below). In most cases the reaction is performed in organic solvents and the hydrolase-catalysed reaction is the irreversible formation of an ester (for example see Figs. 9.3, 9.4, 9.6, 9.12) or amide (for example see Figs. 9.13, 9.14, 9.16). 

Kinetic racemic resolution, as described in Section 4.2.5, suffers from the fact that the ratio of the substrate enantiomers to be resolved changes during the progress of the transformation. In order to circumvent low enantiomeric excess and low yields of the desired product, strategies hke dynamic kinetic resolution (DKR) [59] and parallel kinetic resolution [60] have been introduced. In the first case, racemization, for example, of the substrate is much faster than the undesired transformation of the slower reacting enantiomer, thus keeping an equal ratio of the substrate enantiomers during the whole process. Parallel kinetic resolution makes... 

Epoxides are a familiar sight in the world of kinetic resolutions. As well as being made by kinetic resolution, racemic epoxides can themselves be the substrates in a kinetic resolution. For example, the use of cobalt-salen complexes - something we shall see again in the dynamic kinetic resolution section - can be used to mediate the formation of enantiomerically pure oxazolidinones.20 Enzymes can be used to react with one enantiomer of epoxide.21 And enzymes are a good way to kinetically resolve compounds and can work under surprising conditions - supercritical C02 for example22... 

Dynamic Combinatorial Resolution-Kinetically Resolved DCLs... 

Within physical chemistry, the long-lasting interest in IR spectroscopy lies in structural and dynamical characterization. Fligh resolution vibration-rotation spectroscopy in the gas phase reveals bond lengths, bond angles, molecular symmetry and force constants. Time-resolved IR spectroscopy characterizes reaction kinetics, vibrational lifetimes and relaxation processes. 

A completely different approach, in particular for fast imimolecular processes, extracts state-resolved kinetic infomiation from molecular spectra without using any fomi of time-dependent observation. This includes conventional line-shape methods, as well as the quantum-dynamical analysis of rovibrational overtone spectra [18, 33, 34 and 35]. 

Relaxation kinetics may be monitored in transient studies tlirough a variety of metliods, usually involving some fonn of spectroscopy. Transient teclmiques and spectrophotometry are combined in time resolved spectroscopy to provide botli tire stmctural infonnation from spectral measurements and tire dynamical infonnation from kinetic measurements that are generally needed to characterize tire mechanisms of relaxation processes. The presence and nature of kinetic intennediates, metastable chemical or physical states not present at equilibrium, may be directly examined in tliis way. 

Flynn G W and Weston R E Jr 1995 Glimpses of a meohanism for quenohing unimoleoular reaotions a quantum state resolved pioture Advances in Chemicai Kinetics and Dynamics vol 2B, ed J Barker (Greenwioh, CT JAI Press) pp 359-91... 

Surface SHG [4.307] produces frequency-doubled radiation from a single pulsed laser beam. Intensity, polarization dependence, and rotational anisotropy of the SHG provide information about the surface concentration and orientation of adsorbed molecules and on the symmetry of surface structures. SHG has been successfully used for analysis of adsorption kinetics and ordering effects at surfaces and interfaces, reconstruction of solid surfaces and other surface phase transitions, and potential-induced phenomena at electrode surfaces. For example, orientation measurements were used to probe the intermolecular structure at air-methanol, air-water, and alkane-water interfaces and within mono- and multilayer molecular films. Time-resolved investigations have revealed the orientational dynamics at liquid-liquid, liquid-solid, liquid-air, and air-solid interfaces [4.307]. 

A consistent picture for dynamics of heterogeneous ET has been emerging in the last 5 years with the development of new experimental approaches. Techniques such as AC impedance, modulated and time-resolved spectroscopy, SECM, and photoelectrochemical methods have extended our knowledge of charge-transfer kinetics to a wide range of time scales. This can be exemplified by comparing impedance analysis, which is limited to k of... 

The information amount of process analyses (under which term all time-dependent studies from chemical process control up to dynamic and kinetic studies are summarized) increases by the factor of time resolving power... 

We emphasize that the critical ion pair stilbene+, CA in the two photoactivation methodologies (i.e., charge-transfer activation as well as chloranil activation) is the same, and the different multiplicities of the ion pairs control only the timescale of reaction sequences.14 Moreover, based on the detailed kinetic analysis of the time-resolved absorption spectra and the effect of solvent polarity (and added salt) on photochemical efficiencies for the oxetane formation, it is readily concluded that the initially formed ion pair undergoes a slow coupling (kc - 108 s-1). Thus competition to form solvent-separated ion pairs as well as back electron transfer limits the quantum yields of oxetane production. Such ion-pair dynamics are readily modulated by choosing a solvent of low polarity for the efficient production of oxetane. Also note that a similar electron-transfer mechanism was demonstrated for the cycloaddition of a variety of diarylacetylenes with a quinone via the [D, A] complex56 (Scheme 12). 

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