Optically active centers, epimerization

The (ROP of l-LA was promoted by 17-19 at 30-60 °C upon addition of an excess of /PrOH. The controlled character of the (ROP was established by NMR spectroscopy and MALDI-TOF mass spectrometry no epimerization of the optically active centers was detected. The Sr and Ba complexes 18 and 19 afforded highly active binary catalysts, allowing rapid conversion of the monomer at the remarkably mild temperature of 30 °C (TOF up to 6000 molL LA/molAe h)- However, rapid broadening of the molecular weight distributions was observed at high conversion. The Ca derivative 17 offered the best compromise in terms of activity and control, providing a very efficient binary catalyst for well-controlled (ROP upon... 

Whereas racemization is the complete loss of optical activity with time, epimerization is the reversible interconversion of diastereoisomers to an equilibrium mixture which is not necessarily optically inactive. Diastereoisomers arise from the combination of the two chiral centers in 9, namely the metal centered, R and S, and the resolved (S) optically active ligand center. The diastereoisomers (RS) and (SS) differ in their properties. 

Kinetic work on the isomeric 1,2-diphenylcyclopropanes (Scheme 2) made evident a substantial reduction in Ed and thus implied a stabilization of trimethylene diradical transition structure(s) by phenyl substituents142. In further work with 0.2 M (-)-l,2-diphenylcyclopropane in 1 -butanol, Crawford and Lynch143 uncovered a direct route from one trans antipode to the other at 220.7 °C the measured ratio of rate constants /trac(for loss of optical activity) to kK (for trans to cis geometrical isomerization) was found to be 1.49 0.05 and since krdC is (2k12 + 2/c,). and klc is 2/c,(Scheme 2), the implication is that one-center epimerizations (2kt) are favored over the two-center epimerization process (ka) by... 

The kinetic situations posed by the l,2-d2-cyclopropanes is summarized in Scheme 6. The experimentally accessible rate constants for overall loss of optical activity, k and for approach to cis,trans equilibrium, kh are related to the mechanistic rate constants by the equalities k, = (2ka + 2k) and k, = 4k, with k = (k, + k + kn). Here kt stands for the one-center epimerization rate constant when C(l) C(2) breaks, and for one-center turnover at C(l) when C(l)—C(3) breaks. There are thus two observables and four mechanistic rate constants. If kt kt and kn kn ratios are assigned reasonable values based on assumed kinetic isotope effects, one is left with only kx and kn as unknown mechanistic rate constants to be deduced from the observable k, and kr kinetic parameters. 

All of the optically active compounds prepared by diastereoisomer separation and/or conversion to enantiomers have proved to be configurationally stable at the metal center as long as they are in the solid state. Concerning their behavior in solution, however, the optically active or-gano-transition-metal compounds are divided into two groups (a) compounds configurationally stable at the metal center, which do not racem-ize or epimerize with respect to the metal atom prior to decomposition and (b) compounds configurationally labile at the metal center which racemize or epimerize with respect to the metal atom prior to decomposition. 

Thus, with compounds of type (a), the stereochemistry of substitution, insertion, and cleavage reactions can be studied (8, II), whereas with compounds of type (b), the mechanism of racemization and epimerization at the chiral metal atom can be investigated (II, 92). In the following sections, representative examples of both types of study will be given, from which it will become evident how optically active labels at metal centers in organo-transition-metal compounds contribute to the elucidation of the stereochemical course of reactions. 

The McBride synthesis has been applied to the preparation of chiral phosphetane oxides by the reaction of optically active dichlorophosphines with 2,3,3-trimethyl-l-butene. Thus, myrtanyl-, bornyl-, and isopinocamphenyldichloro-phosphines afforded the corresponding phosphetane oxides having chirality localized on both the phosphorus substituent and the phosphorus center. In all cases, epimeric mixtures are obtained (Equation 22) <1997JOC297>. 

The mild cleavage conditions with NEt3 HF, which do not cause epimerization at centers a to the carbonyl group, are essential for an enantioselective synthesis of y-oxoesters using optically active catalysts 641 in the cyclopropanation step. Up to 50 % ee have been obtained so far 65). Improvements should be possible, if the trans/cis-ratio of the siloxycyclopropane can be increased. Formylesters of type 99 are promising building blocks for further transformations (e.g. synthesis of y-butyrolactones). 

In conclusion, the combination of an enzymatic optical resolution and subsequent chemical transformations of epimerization or racemization of the asymmetric center of the unwanted antipodes have led to the successful development of processes for preparation of the two optically active pyrethroid insecticides. This work will provide a novel feature in the application of enzymes, especially lipases for the industrial production of chiral compounds. 

The development of optical activity by cpl is reported for the D2 molecule 22a [67]. Although both stereogenic centers are reverted, 22a and 22b are not enantiomers. One of the four hydrogen atoms drawn in Eq. (33) may be replaced by other groups like -OCH3 [84] or -NHCOCH3 [85], and the results of the irradiation of these molecules exclude a simple epimerization at the two bridgehead carbon atoms. 

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. 

The stereochemical course of the photoinduced walk rearrangement sensitized by benzophenone was examined for the optically active ester (-)-47 and nitrile (+)-48 (76). Similarly, as in the corresponding thermal rearrangement (Figure 5), the inversion process is preferred in both systems (stereoselectivity for 47 >92%, for 48 >76%). In nitrile 48 an additional racemization made of the starting material due to a one-center epimerization at C-7 competes with the rearrangement. Stereoselective diradical processes of the triplet states were proposed to explain these results. 

The addition of cyanide to simple aldoses is essentially quantitative in solutions buffered at pH 9.1 increased acidity causes diminished reaction rates. The reaction can be conveniently effected using a solution of sodium cyanide and calcium chloride, but varied conditions may be required in order to obtain desired proportions of the epimeric products. The latter arise from the creation of a new asymmetric center, and are generally not produced in equal amoimts because of the asymmetric nature of syntheses using optically active starting materials. The epimeric preference may be so high as to give essentially quantitative yields of one product. For ex-... 

---