Enantioselective oxirane isomerization

Turning to enzymatic hydration, we see from the data in Table 10.1 that phenanthrene 9,10-oxide Fig. 10.10, 10.29) is an excellent substrate for epoxide hydrolase. Comparison of enzymatic hydration of the three isomeric phenanthrene oxides shows that the Vmax with the 9,10-oxide is greater than with the 1,2- or the 3,4-oxide the affinity was higher as well, as assessed by the tenfold lower Km value [90]. Furthermore, phenanthrene 9,10-oxide has a plane of symmetry and is, thus, an achiral molecule, but hydration gives rise to a chiral metabolite with high product enantioselectivity. Indeed, nucleophilic attack by epoxide hydrolase occurs at C(9) with inversion of configuration i.e., from below the oxirane ring as shown in Fig. 10.10) to yield the C-H9.S, 10.S )-9,10-dihydro-9,10-diol (10.30) [91],... 

The growing interest in enantioselective isomerization of meso oxiranes to allylic alcohols arises from the ready availabihty of starting materials and the synthetic value of the homochiral products. First apphed to simple meso cycloalkene oxides, this methodology has been successfully exteuded to fuuctioualized meso oxiranes, and even to the kinetic resolution of racemic oxiranes, demonstrating its potential in accessing highly advanced synthons. 

The enantioselective base-promoted rearrangement of oxiranes was achieved by White-sell and Fehnan in 1980. Various homochiral lithium amides were used for the isomerization of cyclohexene oxide with an enantiomeric excess (ee) up to 36% with the employment of 50 in refluxing THF (Scheme 24). 

Numerous HCLA have been developed and used for the enantioselective isomerization of oxiranes to allylic alcohols and, in most cases, their efficiency strongly depends on the structure of the oxirane. The HCLA species can be divided into two groups monohthiated vicinal diamines or ether-amines and dilithiated diamines or amido-alcoholates. 

Hi. Role of additive. There are some reports in the literature of the beneficial effect of powerful donor solvents such as DBU on the reactivity and enantioselectivity of HCLA-mediated oxirane rearrangements for both stoichiometric and catalytic processes. However, this effect is not general (see above) and the role of such additives is still unclear. In one study, the influence of the concentration of DBU on the relationship between the ee s of catalyst and the product for the enantioselective isomerization of cyclohexene oxide mediated by substoichiometric amount of HCLA 56a (20 mol%) in the presence of LDA (2 equiv) has been investigated. At high DBU concentration (6 equiv), the enantiomeric... 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

The lithium diethylamide-promoted isomerization of cis- and traws-cyclooctene oxide affords different products or the same products in different proportions. This lack of convergence rules out carbene 227 as a common intermediate (Scheme 1-173). Moreover, the c/s-oxirane reacts with isopropyllithium in the presence of (-)-sparteine enantioselectively. ... 

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