Disubstituted alkyl epoxides

TABLE 8.4 Selected Kinetic Resolutions of Some gem-Disubstituted Alkyl Epoxides ... 

With catalyst 117, they were able to epoxidize a large number of l,2.disubstituted enals with excellent diastereomeric ratios and excellent enantioselectivities (Eq. (a), Scheme 12.32). In addition, the authors were able to epoxidize 3,p-disubstituted (alkyl groups) a,(3-unsaturated aldehydes. This method represents one of the gold standards for the synthesis of trisubstituted epoxides (Eq. (b). Scheme 12.32). 

When gem-disubstituted epoxides (122) are treated with Grignard reagents (and sometimes other epoxides), the product may be 123, that is, the new alkyl group may appear on the same carbon as the OH. In such cases, the epoxide is isomerized to an aldehyde or a ketone before reacting with the Grignard reagent. Halohydrins are often side products. 

While alkylation of terminal epoxides is reliable, attempted alkylations of 1,2-disubstituted epoxides have proved capricious. An unsuccessful approach to the swinholides, which called for the alkylation of cyanohydrin 47 with epoxide 48, is one such example. In the event, alkylation cleanly produced imidate 49, rather than the expected product 50 [27] (Eq. 14). 

Generally monosubstituted and dx-l,2-disubstituted epoxides are good substrates for EH while tri-, tetra or tra s-l,2-disubstituted ones are poor or non-substrates. Resolutions of epoxides using microsomal epoxide hydrolases, mEHs show that cis-2-alkyl substituted styrene oxides gave very high E-values when R=Me or Et (Figure 2.18a). A series of cis-... 

Lithiation of 2-bromo-3,3-disubstituted-methylenecyclopropanes by metal halogen exchange reaction with EtLi in ether, followed by alkylation with epoxides, gave selectively ring-alkylated /8-alcohols, derived from attack at the epoxide primary carbon (equation 299). When R1 R2 a mixture of isomers is obtained369. 

Syntheses of 16,17-disubstituted oestra-l,3 5(10),14-tetraene 3-methyl ethers involved reaction of the corresponding 16,17-epoxides with various nucleo-philes and similar reactions of the 17,20-epoxides (300) gave a range of androstanes (301). A series of 16j8-alkylated androstanes and oestranes has... 

Iron-mediated oxygen transfer is also at play in the chloroperoxidase (CPO) catalyzed epoxidation of simple alkenes, which has the added advantage of providing high enantiomeric excesses. For example, c/s-2-heptene 35 is converted to the chiral epoxide 36 in 78% yield. However, the protocol is generally limited to fairly accessible disubstituted alkenes the more imbedded olefin of cis-3-heptene only undergoes 12% conversion, while the epoxides derived from terminal olefins tend to alkylate the enzyme and serve as suicide inhibitors <0374701>. 

Cobalt(iii) diketonate complexes generate alkyl peroxo adducts that can oxidize alkenes to oxiranes <1999IC1603>. 0-Phenylenebis(oxamate)-Iigated square-planar cobalt(iii) complexes catalyze high-yield epoxida-tions of unfunctionalized tri- and disubstituted alkenes <1997TL2377>. Low yields are obtained with terminal alkenes. Terminal alkenes can be converted smoothly to aldehydes using an epoxidation-isomerization with ruthenium(ii) porphyrin catalysts <2004AGE4950>. 

Substrate Scope. Best results in the (salen)Mn -catalyzed epoxidation reaction have been obtained with cis-disubstituted, conjugated alkenes (Table 1). Epoxidation of 2,2-dimethylchromene derivatives occurs with especially high selectivity (>97% ee). frans-Disubstituted alkenes are epoxidized with low selectivity (20-50% ee), as are simple alkyl-substituted alkenes. 

The cyclization in Step B is an improvement of Butler s procedure for the synthesis of which employs less convenient reagents, KNH and l-bromo-3-chloroacetone acetal. Beside the acetals derived from neopentyl glycol, those derived from ethanol, 1,3-propanediol and 2,4-pentanediol have been synthesized by the present method. The second part of Step B involves the formation and the electrophilic trapping of cyclopropenyl anion 2, which is the key element of the present preparations. Step B provides a simple route to substituted cyclopropenones, but the reaction is limited to alkylation with alkyl halides. The use of lithiated and zincated cyclopropenone acetal, on the other hand, is more general and permits the reaction with a variety of electrophiles alkyl, aryl and vinyl halides, Me3SiCl, Bu3SnCl, aldehydes, ketones, and epoxides. Repetition of the lithiation/alkylation sequence provides disubstituted cyclopropenone acetals. 

The reaction involving the alkylation of p-hydroxyalkyl selenides to give p-hydroxyalkylselenonium salts which are then cyclized with a base is by far the most general. It allows Ae synthesis of a large variety of epoxides such as tenninal, a,a- and a,p-disubstituted, tri-33-> and tetra-substituted, 3,i88 as oxaspiro[2.0.n]-hexanes, -heptanes and -octanes (Scheme 161, g Scheme 162, d Scheme 164, d Scheme 165, b) - and vinyl oxiranes (Schemes 166 and 181)33 -239 from both p-hydroxy-alkyl methyl33- 3 3 22>.222j36,263 phenyl selenides. ... 

Deoxygenation of epoxides. Di-, tri-, and tetrasubstituted epoxides are converted into alkenes by treatment with PI3 (or P2I4). The reaction occurs most readily with a,j8-disubstituted epoxides and with >98% retention of configuration. With more substituted epoxides addition of pyridine or triethylamine improves yields by preventing formation of alkyl iodides. 

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