Epoxides with alcoholates

Scheme4.78. Reactions of epoxides with alcohols under basic reaction conditions[329, 351—353], Pol= polystyrene or TentaGel R= alkyl.

A. Gonzalez, J. M. Cu(BF4)2-Catalyzed ringopening reaction of epoxides with alcohols at room temperature. Org. Lett. 2002, 4, 2817-2819. 

R is usually CH3-, C6H5-, or m-CIC6H4-Ring opening of epoxides with alcohols (8.8)... 

Epoxide opening. Optically active trans-1,2-diol monoethers are readily obtained by the catalyzed reaction of epoxides with alcohols in the presence of the BINOL complexes and molecular sieves 4A. Similarly, p-hydroxy sulfides are formed. ... 

Lanthanide(ni) on ion exchange resins catalyse Mukaiyama aldol reactions in aqueous media, acetalisations, additions of silyl enol ethers to imines, saz-Diels-Alder reactions and the ringopening of epoxides with alcohols as depicted in Scheme 3.6.7. 

Jacobsen and Ready <0IJA2687> have reported on the development of a highly aetive cyclic oligosalen catalyst (66), which is remarkably effective in promoting the asymmetric ring opening of epoxides by water and alcohols. For example, exposure of the notoriously recalcitrant substrate cyclohexene oxide (67) to water in methylene chloride/acetonitrile and 1.5 mol% of catalyst 66 led to smooth conversion to the chiral diol 68 in 98% yield and 94% ee. This catalyst is also effective in the kinetic resolution of epoxides with alcohols (i.e., 69 71)<01JA2687>. 

Ring opening of oxiranes is catalyzed by zirconium or hafnium complexes in the presence of nucleophiles. Cp2ZrCl2 was used as a catalyst for ring opening of substituted epoxides with alcohols under mild conditions. The corresponding alkoxyalcohols were obtained in good yields. As shown in Equation 38, when trans-stilbene oxide was subjected to the reaction in methanol, a mixture of anti-and syn isomers were obtained [43]. 

Miscelleneous Applications. The method of choice for the regioselective opening of benzylic and tertiary epoxides with alcohols (eq 13) appears to be a reaction mediated by organ-otin phosphate condensate (OPC) , which is readily prepared from DBTO and tributyl phosphate. DBTO catalyzes rearrangement of 3-hydroxy-2-oxo carboxylic acid esters (eq 14), a reaction reminiscent of a similar one mediated by the enzyme reductoisomerase. DBTO has been used as a catalyst for the addition of Azidotrimethylsilane to nitriles for the production of tetrazoles (eq 15). 

Prepared by epoxidation of styrene with per-oxyelhanoic acid. Reactions are similar to those of aliphatic epoxides (s e, e.g. ethylene oxide). Reacts with alcohols to give mono-ethers, e g. PhCH(0Me)CH20H. Phenols give resins. 

ARCO has developed a coproduct process which produces KA along with propylene oxide [75-56-9] (95—97). Cyclohexane is oxidized as in the high peroxide process to maximize the quantity of CHHP. The reactor effluent then is concentrated to about 20% CHHP by distilling off unreacted cyclohexane and cosolvent tert-huty alcohol [75-65-0]. This concentrate then is contacted with propylene [115-07-1] in another reactor in which the propylene is epoxidized with CHHP to form propylene oxide and KA. A molybdenum catalyst is employed. The product ratio is about 2.5 kg of KA pet kilogram of propylene oxide. 

Displacement of activated chlorine atoms also proceeds with certain types of organic compounds, but only in the presence of Lewis acid catalysts. Particular examples include epoxides, polyhydric alcohols, trialkylphosphites (12), and P-aminocrotonates (13). These additives are commonly used in conjunction with metallic stabilizers to provide complete, high performance, commercial stabilizer packages. 

Hydrogen Sulfide andMercaptans. Hydrogen sulfide and propylene oxide react to produce l-mercapto-2-propanol and bis(2-hydroxypropyl) sulfide (69,70). Reaction of the epoxide with mercaptans yields 1-aLkylthio- or l-arylthio-2-propanol when basic catalysis is used (71). Acid catalysts produce a mixture of primary and secondary hydroxy products, but ia low yield (72). Suitable catalysts iaclude sodium hydroxide, sodium salts of the mercaptan, tetraaLkylammonium hydroxide, acidic 2eohtes, and sodium salts of an alkoxylated alcohol or mercaptan (26,69,70,73,74). 

The cleavage of steroidal epoxides with Grignard reagents leads exclusively to alcohols with the tra 5-diaxial orientation of the hydroxyl group and the newly introduced alkyl group. °... 

Vanous chlorofluoroacetones on reaction with pentafluorophenyllithium give pentalluorophenylchlorofluoro tertiary alcohols [34, which on treatment with alcoholic potassium hydroxide produce epoxides (equation 12)... 

Although the limited examples of AE reactions on 2,3Z-substituted allyl alcohols appear to give product epoxides in good enantioselectivity, the highly substituted nature of these olefins can have a deleterious effect on the reactivity. For example, Aiai has shown that the 2,3E-substituted allyl alcohol 30 can be epoxidized with either (-)-DET or (+)-DET in good yields and enantioselectivity. However, the configurational isomer 32 is completely unreactive using (-)-DET, even after a 34 h reaction time. 

The reaction of olefins,alcohols,and epoxides > with or at high temperatures over catalysts such as... 

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

Begue and coworkers recently achieved an improvement in this method by performing the epoxidation reaction in hexafluoro-2-propanol [120]. They found that the activity of hydrogen peroxide was significantly increased in this fluorous alcohol, in relation to trifluoroethanol, which allowed for the use of 30% aqueous H202. Interestingly, the nature of the substrate and the choice of additive turned out to have important consequences for the lifetime of the catalyst. Cyclic dis-ubstituted olefins were efficiently epoxidized with 0.1 mol% of MTO and 10 mol%... 

Although the enantioselective intermolecular addition of aliphatic alcohols to meso-epoxides with (salen)metal systems has not been reported, intramolecular asymmetric ring-opening of meso-epoxy alcohols has been demonstrated. By use of monomeric cobalt acetate catalyst 8, several complex cyclic and bicydic products can be accessed in highly enantioenriched form from the readily available meso-epoxy alcohols (Scheme 7.17) [32]. 

Pineschi and Feringa reported that chiral copper phosphoramidite catalysts mediate a regiodivergent kinetic resolution (RKR) of cyclic unsaturated epoxides with dialkylzinc reagents, in which epoxide enantiomers are selectively transformed into different regioisomers (allylic and homoallylic alcohols) [90]. The method was also applied to both s-cis and s-trans cyclic allylic epoxides (Schemes 7.45 and 7.46,... 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

The cyclohexyloxy(dimethyl)silyl unit in 8 serves as a hydroxy surrogate and is converted into an alcohol via the Tamao oxidation after the allylboration reaction. The allylsilane products of asymmetric allylboration reactions of the dimethylphenylsilyl reagent 7 are readily converted into optically active 2-butene-l, 4-diols via epoxidation with dimethyl dioxirane followed by acid-catalyzed Peterson elimination of the intermediate epoxysilane. Although several chiral (Z)-y-alkoxyallylboron reagents were described in Section 1.3.3.3.3.1.4., relatively few applications in double asymmetric reactions with chiral aldehydes have been reported. One notable example involves the matched double asymmetric reaction of the diisopinocampheyl [(Z)-methoxy-2-propenyl]boron reagent with a chiral x/ -dialkoxyaldehyde87. 

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