Curtin-Hammett kinetics

Figure 12.9. Curtin-Hammett kinetics forethene/CO insertion...

Figure 2b shows the other extreme, whereby the rate of epimerization is fast relative to the rate of substitution. In this case, Curtin-Hammett kinetics apply, and the product ratio is determined by AAG. In the specific case of organolithium enantiomers that are rendered diastereomeric by virtue of an external chiral ligand, such a process may be termed a dynamic kinetic resolution. Both of these processes are also known by the more general term asymmetric transformation One should be careful to restrict the term resolution to a separation (either physical or dynamic) of enantiomers. An asymmetric transformation may also afford dynamic separation of equilibrating diastereomers, but such a process is not a resolution. "... 

If all the cyclizations and cleavages are rapid relative to H-atom transfer, then the product distribution depends on the equilibrium constant between (49) and (50) and the rate of hydrogen atom transfer to (49) and (50) (Curtin-Hammett kinetics). 

Reduction of C(5)-substituted 2-hydroxychromans selectively provides 2,4-cis-chromans using large silane RsSiH reductants and 2,4-frans-chromans using the smaller silane PhSiH3. The stereochemical outcome has been rationalized on the basis of a Curtin-Hammett kinetic situation arising from hydride delivery to two different conformations of an intermediate oxocarbenium ion.363... 

Keywords rf- Imine complex Zirconaaziridine Curtin-Hammett kinetics ... 

The synthesis of amino acid esters can be carried out enantioselectively when optically active EBTHI zirconaaziridines are used. After diastereomeric zir-conaaziridines are generated and allowed to equilibrate (recall Scheme 3), the stereochemistry of the chiral carbon center in the insertion product is determined by competition between the rate constants kSSR and ksss for the epimerization of zirconaaziridine diastereomers and the rate constants [EC] and ks[EC] for ethylene carbonate (EC) insertion (Eq. 31) [43]. When kR[EC] and ks[EC] are much greater than kSSR and ksss> the product ratio reflects the equilibrium ratio as shown in Eq. 32. However, the opposite limit, where epimerization is much faster than insertion, is a Curtin-Hammett kinetic situation [65] where the product ratio is given by Eq. 33. 

Virtually all of the synthetic applications of chiral dipole-stabilized organolithiums reported to date have the C— Li bond in an allylic or benzylic system. The most important consequence of this fact is that the two stereoisomers shown in Figure 3 can interconvert by pyramidal inversion. Therefore, the stereoselectivity of the deprotonation is irrelevant to the stereoselectivity as manifested in the product dia-stereomer ratio. The source of the selectivity in the organolithium alkylation step has not been determined. The available data do not permit a distinction between at least three possibilities thermodynamic control as determined by the equilibrating organolithium diastereomers, - kinetic control according to Curtin-Hammett kinetics,or increased carbon-lithium covalency at low temperature. ... 

Thus Karabatsos concluded that the rationale for Cram s rule was incorrect [10]. In 1967, he published a new model, which took into account the approach of the nucleophile from either side of all three eclipsed conformers [10]. He noted that the enthalpy and entropy of activation for Grignard or hydride additions to carbonyls are 8 to 15 kcal/mole and -20 to -40 eu, respectively. Since the barrier to rotation around the sp -sp carbon-carbon bond is much lower [12], the selectivity must arise from Curtin-Hammett kinetics [13,14]. Of the six possible conformers (Figure... 

Note that the illustrated conformation has the acrolein oriented in an 5-cis conformation. This is in contrast to the usual 5-trans conformation of acroleins coordinated to a Lewis acid (Figure 6.13a), but it is supported by the fact that cyclo-pentadiene adds to the opposite face of acrolein itself [216]. It is likely that both s-cis and 5-trans dienophile conformers are present, and that the -cis conformer is more reactive. In other words, Curtin-Hammett kinetics [235] are operative. The rationale for this increased reactivity is as follows the j-trans conformation of 2-bromoacrolein would place the bromine above the indene ring. Cycloaddition to the top (Si) face of the 5-trans conformer would force the bromine into closer proximity to the indene as C2 rehybridizes from sp2 to sp3, a situation that is avoided in cycloaddition to the top (Re) face of the 5-cis conformer. 

Figure 7.7. The asymmetric hydrogenation of A -acetyl dehydrophenylalanine ester as an example of Curtin-Hammett kinetics. Energy values taken from ref. [111].

The treatment of adduct 198 with benzyl bromide led to the formation of tertiary phosphine (Pp)-199 with 72-78% ee and to initial catalyst Pt(Me-Duphos)(Ph)(Br) which confirms the proposed mechanism. The substitution at the tricoordinated phosphorus atom of the secondary phosphine 198 proceeded with retention of absolute configuration at phosphorus, according to classical representations. On the basis of these results, the authors established that the enantioselectivity was determined mainly by the thermodynamic preference for one of the interconverting diastereomers of (5p)-198 U (Pp)-198, although their relative rates of alkylation were also important (Curtin-Hammett kinetics) (Scheme 64) [122]. 

Detailed analyses of Curtin—Hammett kinetics were given by Zefirov and by Seeman and co-workers. °°... 

It is the combination of these twin goals that has led to the evolution of classical kinetic resolution into dynamic kinetic resolution (DKR). In such a process, it is possible in principle to obtain a quantitative yield of one of the enantiomers. Effectively, DKR combines the resolution step of kinetic resolution, with in situ equilibration or racemisation of the chirally labile substrate (Figure i.2). In DKR, the enantiomers of a racemic substrate are induced to equilibrate at a rate faster than that of the slow-reacting enantiomer in reaction with the chiral reagent (Curtin-Hammett kinetics). If the enantioselectivity is sufficient, then isolation of a highly enriched non-racemic product is possible with a theoretical yield of 100% based on the racemic substrate. 

The stereoselectivity of the Heck reaction is governed by hydride elimination. In the majority of cases, the elimination obeys the Curtin-Hammett kinetic control principle and the ratio of E- and Z-isomers reflects the relative energy of the respective transition states. Unless R (see 18) is very small (for example CN), the -isomer is predominant and the reaction is highly stereoselective. ... 

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