Epoxidations group selectivity

R2Cu(CN)Li2 reaction with vie-epoxy mesylatesA higher-order cuprate reacts selectively with the epoxide group of the epoxy mesylate 1 to provide 2 with inversion at C3. Ring closure of 2 furnishes the epoxide 3, which reacts with a second equivalent of the higher-order cuprate to furnish meso-4, with inversion at both C, and C3. This two-step reaction provides a route to acyclic alcohols with useful stereocontrol at both adjacent centers. 

The overall reaction catalyzed by epoxide hydrolases is the addition of a H20 molecule to an epoxide. Alkene oxides, thus, yield diols (Fig. 10.5), whereas arene oxides yield dihydrodiols (cf. Fig. 10.8). In earlier studies, it had been postulated that epoxide hydrolases act by enhancing the nucleo-philicity of a H20 molecule and directing it to attack an epoxide, as pictured in Fig. 10.5, a [59] [60], Further evidence such as the lack of incorporation of 180 from H2180 into the substrate, the isolation of an ester intermediate, and the effects of group-selective reagents and carefully designed inhibitors led to a more-elaborate model [59][61 - 67]. As pictured in Fig. 10.5,b, nucleophilic attack of the substrate is mediated by a carboxylate group in the catalytic site to form an ester intermediate. In a second step, an activated H20... 

E. C. Dietze, J. Stephens, J. Magdalou, D. M. Bender, M. Moyer, B. Fowler, B. D. Hammock, Inhibition of Human and Murine Cytosolic Epoxide Hydrolase by Group-Selective Reagents , Comp. Biochem. Physiol., B 1993, 104, 299 - 308. 

More than a decade of experience on Sharpless asymmetric epoxidation has confirmed that the method allows a great structural diversity in allylic alcohols and no exceptions to the face-selectivity rules shown in Fig. 10.1 have been reported to date. The scheme can be used with absolute confidence to predict and assign absolute configurations to the epoxides obtained from prochiral allylic alcohols. However, when allylic alcohols have chiral substituents at C(l), C(2) and/or C(3), the assignment of stereochemistry to the newly introduced epoxide group must be done with considerably more care. 

Aluminum-alkynyl covalent bonds, characteristics, 9, 249-250 Aluminum-aluminum bonds in A1(I) compounds, 9, 261 in Al(II) compounds, 9, 260 Aluminum aryloxides, reactivity, 9, 254—255 Aluminum(III)ates, in organic group-selective transfers, 9, 279 Aluminum(I)-boron bonds, characteristics, 9, 263 Aluminum(III)-boron exchange, process, 9, 266 Aluminum-calix[4]arene catalyst, for alternating epoxide-CC>2 co-polymerization, 11, 617... 

Diastereoselective macrocycUzation. A ke> step in a synthesis of the 14-membered cembranoid asperdiol (4) involves intramolecular ( yclization of the aldehydo allylic bromide (1) with chromium(II) chloride. The intermolccular version of this reaction is known to be anf/-selective (8,112). Treatment of racemic 1 with CrCl, (5 equiv., THF) results in a 4 1 mixture of the two anti-diastereomers 2 and 3 in 64% combined yield. The stereochemistry of this cyclization is evidently controlled by the remote epoxide group. The natural product was obtained by deprotection of 2 (Na/NH, 51% yield). 

Hydrogenation catalyst. Russell and Hoy have described a nickel boride catalyst which is useful for selective reduction of C=C bonds without hydrogenolysis of liydruxylic subslilueiils or hydrogenation of carbonyl or epoxide groups. The black colloidal catalyst is prepared by reduction of nickel acetate in ethanol with. 0M sodium borohydridc solution. 

A synthetically useful procedure for the one-pot conversion [1] of vicinal diols into epoxides involves selective mono-activation of one hydroxyl group (by reaction with 1 equiv. of tosyl... 

Although much more selective than the uncatalyzed reaction, the base-catalyzed reaction has some dependence on stoichiometry. At a ratio of epoxide to acid of 1 1, essentially all the product is the hydroxy ester. However, when an excess of epoxide groups is present. Reaction 7 proceeds until all the acid is consumed, after which the epoxide-hydroxyl reaction (Reaction 9) starts. This is illustrated in Figure 4. 

Scheme 8.10. Reaction of divinyl carbinol under (+)-AE conditions as an example of enantiotopic group selectivity in epoxidation chemistry. Matched cases of enantiofacial selectivity are shown with bold arrows. Qualitative rate differences are on the order kj k2, ks k4 (without specifying an order for k2 vi. k3 (however, cf. Scheme 8.8b). Note that the products arising from the pairs ki/k3 and k2/k4 are enantiomers.

Scheme 8.11. (a) Group-selective ring-opening of meso epoxides by nucleophiles leads to enantioselective syntheses of 1,2-difunctionalized compounds, (b) Azido alcohol synthesis from epoxides and trimethylsilyl azide as catalyzed by (salen)CrCl complexes (see Scheme 8.6a for general structures of salen catalysts)... 

The benzylic oxidation depicted in the second step of Scheme 8.28b is actually a formal group-selective differentiation of diastereotopic C-H bonds, since asymmetric epoxidation occurs prior to hydroxylation [125]. However, the reaction is an interesting example of a kinetic resolution that depends on the fact that the catalyst used reacts with the two epoxides at different rates, apparently because the chiral catalyst system ... 

Scheme 8.28. Formally group-selection insertion of oxygen into enantiotopic C-H bonds, (a) An asymmetric Kharasch reaction [124], The catalyst is similar to that shown in Scheme 8.12, except that each oxazoline bears two methyl substituents at C-5. (b) Kinetic resolution of dihydronaphthalenes [125]. The reaction uses a Jacobsen epoxidation catalyst (Scheme 8.6, type A).

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