Chemoselective epoxidation

For acyclic allylic alcohols, very little a,p-unsaturated enone formation was observed besides epoxidation. Chemoselectivity was much less for cyclic allylic alcohols, for which oxidation of fhe allylic alcohol group competed significantly with epoxidation. In the case of 2-cyclohexenol as the substrate, the enone was even found to be the main product. A comparative sandwich POM-catalyzed epoxidation study of various (subsfifufed) cycloalkenols revealed that the enone versus epoxide chemoselectivity is controlled by the C=C-C-OH dihedral angle Ma in the allylic alcohol substrate. The more this dihedral angle deviates from fhe optimum C=C-C-OW dihedral angle otw for allylic acohol epoxidation, the more enone is formed (Fig. 16.5). 

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

In transforming bis-ketone 45 to keto-epoxide 46, the elevated stereoselectivity was believed to be a consequence of tbe molecular shape — tbe sulfur ylide attacked preferentially from tbe convex face of the strongly puckered molecule of 45. Moreover, the pronounced chemoselectivity was attributed to tbe increased electropbilicity of the furanone versus the pyranone carbonyl, as a result of an inductive effect generated by tbe pair of spiroacetal oxygen substituents at tbe furanone a-position. ... 

It has been reported that an allylic C-Si bond can be cleaved by tetrabutylammonium fluoride to give an anionic allylic species, which chemoselectively adds to carbonyl compounds (nitriles, esters, and epoxides failed) to form homoallylsilyloxy compounds13. 

It is interesting to note the chemoselectivity of the reaction double and triple bonds, thioketals, epoxides, nitro and sulfone groups and usual functions are not affected. 

The outstanding chemoselectivity of Cp2TiCT was amply demonstrated by Merlic [50,51] and by Dotz [52] who employed a, /3-unsaluraled tungsten and chromium carbenes as radical traps for C - C bond formation. In the latter contribution the very acid sensitive glycal epoxides were used with good success. An example is shown in Scheme 8. 

The process is assumed to take place by a chemoselective attack of the dianion 2-223 at the bromomethyl group of 2-221 and subsequent nucleophilic attack of the resultant monoanion 2-224 onto the epoxide moiety to give 2-225. Use of the sodium-lithium-salt 2-223 of the dicarbonyl compound 2-220, the reaction temperature as well as the Lewis acid LiC104, are crucial. The reaction seems to be quite general, since various 1,3-dicarbonyl compounds can be converted into the corresponding furans. 

The current research areas with ruthenium chemistry include the effective asymmetric hydrogenation of other substrates such as imines and epoxides, the synthesis of more chemoselective and enantioselective catalysts, COz hydrogenation and utilization, new methods for recovering and recycling homogeneous catalysts, new solvent systems, catalysis in two or three phases, and the replace-... 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

Several aspects are particularly noteworthy. Good chemoselectivity is noted in the compatibility with epoxides, esters, olefins, and alcohols. Entries 44 and 45 demonstrate the chemoselectivity between an unsaturated and saturated ketone. 

An unusual case of intramolecular competition (chemoselectivity, see Chapt. 1 in [la]) between ester and oxirane occurs in the detoxification of (oxiran-2-yl)methyl 2-ethyl-2,5-dimethylhexanoate (10.49), one of the most abundant isomers of an epoxy resin. The compound is chemically very stable, i.e., resistant to aqueous hydrolysis, but is rapidly hydrolyzed in cytosolic and microsomal preparations by epoxide hydrolase and carboxylesterase, which attack the epoxide and ester groups, respectively [129], The rate of overall enzymatic hydrolysis was species dependent, decreasing in the order mouse > rat > human, but was relatively fast in all tissues examined (lung and skin as portals of entry, and liver as a further barrier). In mouse and rat lung microsomes, ester hydrolysis was 3-4 times faster than epoxide hydration, whereas the opposite was true in human lung microsomes. 

A more recent approach to the epoxidation of allylic alcohols makes use of a vanadium polyoxometallate, together with a sterically demanding chiral tartrate (or TADDOL) -derived hydroperoxide, to give a highly chemoselective, regiose-lective and enantioselective outcome (Figure 11.2). ... 

Direct epoxidation of compound 20 with Bu OOH in the presence of VO(acac)2 [10], proceeded chemoselectively to give the epoxide 21 which was regioselectively opened with UAIH4 to afford the 1,2-diol 22 (76%). X-ray diffraction analysis of this compound confirmed the assigned stereochemistry for intermediates 20-22. 

Alkylation of organomanganese reagents with alkyl bromides can also be improved by addition of CuCI (3 mol%). The reactions proceed at room temperature and are complete within a few hours [123, 130], The opening of epoxides is also improved under these conditions. The reaction also features good chemoselectivity, tolerating the presence of sensitive functions such as ketones (Scheme 2.59) [130]. 

The stereo- and chemoselective epoxidation a,j9-unsaturated ketones is best achieved employing the biphasic conditions (PLL/UHP/DBU/THF), (see above). 

Our preliminary experiments have provided the first example of Lewis acid promoted C-C bond heterolysis of epoxides and productive cycloaddition (eq 7). Under the influence of TiCl4-(THF)2 (2 equiv), epoxide 26 reacts with methyl pyruvate to provide acetal 27 (52% isolated yield), along with C-O cleavage product 28 (23 °C, 3 h). The diaste-reoselectivity for formation of 27 is 2.3 1. We have performed the analogous reaction in the absence of a Lewis acid the thermal reaction requires several days at 110 °C and gives a diastereomer ratio (dr) of ca. 1.3 1... Although not optimized from the standpoint of chemoselectivity, these results are promising because of the relatively low reaction temperature and potential for enhanced diastereocontrol. 

Last but not least, enzymatic polymerization is more chemoselective than chemical polymerization as witnessed, for instance, by the successful polymerization of functionalized lactones bearing unsaturations and epoxides (Fig. 31) [150]. 

The process proved to be very chemoselective, since functionalities of the starting corticosteroids, such as A4-3-keto, A1,4-3-keto, 11 p-hydroxyl, and 9p,llp-epoxide, remained intact [136]. 

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