Epoxides allylic systems

Scheme 7.4 illustrates some of the important synthetic reactions in which organolithium reagents act as nucleophiles. The range of reactions includes S/v2-(ype alkylation (Entries 1 to 3), epoxide ring opening (Entry 4), and formation of alcohols by additions to aldehydes and ketones (Entries 5 to 10). Note that in Entry 2, alkylation takes place mainly at the 7-carbon of the allylic system. The ratio favoring 7-alkylation... 

The C = C bond in the hydroxy allylic system of a fluoroalkanol can be selectively epoxidized without affecting the hydroxy group. Enantioselective epoxidation of racemic unsaturated fluoro alcohols by using the chiral Sharpless reagent can be exploited for the kinetic resolution of enantiomers. The recovered stereoisomer (e.g., 1) has 14-98% enantiomeric excess.165... 

Little is known about transition metal catalyzed epoxidation of simple allylic amides. The easily removable trichloroacetyl group is suitable as /V-substituent in the molybdenum-catalyzed epoxidation of (Z)-allylic systems with rm-butyl hydroperoxide, which produces the. sv -com-pound with appreciable selectivity21. 

Beside the Grignard and other C-C bond-forming reactions, a number of functional group transformations may also serve as an entry into allylic systems. Some of them, namely the reduction of a, -unsaturated carbonyl compounds (products of crotonic condensation), halogenation of alkenes at the allylic position with Af-bromosuccinimide (NBS) and epoxide isomerization, are shown in Scheme 2.56. 

Hydrogen peroxide or t-butyl hydroperoxide may be used in the presence of a catalyst such as sodium tungstate(VI) or vanadyl acetylaceto-nate [ MeC0CH=C(0 )Me 2V0] for the epoxidation of allylic alcohols. The stereochemistry of the hydroxyl group has a profound effect on the stereochemistry of epoxidation. A system which has been applied to allylic alcohols, to make optically active epoxides, utilizes titanium(rV) isopropoxide, t-butyl hydroperoxide and either of the enantiomeric forms of diethyl tartrate. This system forms chiral epoxides of predictable stereochemistry. When the reactivity of epoxides is combined with the... 

It can be seen that, under similar conditions, the reactivity of the dialkyl sulfides is directly linked to their molecular size Et2 S > Pr2 S > Bu2 S, and saturated sulfides are more reactive than allyl or aryl sulfides Pr2 S > Me S Allyl > Allyb S > Me S Ph > Ph2 S. These results can be explained, first, if we take into account the relative easiness of thioethers accessibility to the Ti active sites of the catalytic species located in the zeolite framework. The diffusion of the bulkier molecules, such as Ph2S is very difficult even inside the large pores of Ti-beta zeolite. Secondly, the reactivity of thioethers is in agreement with the nucleophilicity of the sulfur atom, so that alkyl sulfides are more easily oxidized than allyl or aryl sulfides by H2O2 (an electrophilic oxidant) in agreement with reported results [1-9]. It must be pointed out, that in the case of allyl methyl sulfide and di-allylsulfide, the epoxidation of the allyl system is not observed under our experimental conditions. 

Allylic systems frequently represent very popular substrates for the synthesis of epoxides. For example, hydrogen bonding proved influential during diastereoselective epoxidation of a series of cyclic and acyclic allylic amines... 

The synthesis in Scheme 13.38 combines elements of a biomimetic-type polyene cyclization with a rearrangement similar to that just described in Scheme 13.37. The early stages of the synthesis culminate in the construction of the allylic alcohol in step B. In step C, it is epoxidized using the stereoselective VO(t-BuOOH) method (Section 12.2.1). This epoxidation provides the key intermediate for the polyene cyclization. The mild Lewis acid FeCla is used to promote the cyclization, which terminates in an electrophilic substitution of the methoxyphenyl substituent. Steps E and F convert the methoxyphenyl ring to a diene. This diene undergoes a Diels-Alder reaction in step G. After catalytic reduction of the double bond, the anhydride is subjected to an oxidative bis-decarboxylation (see Section 12.4.2 for discussion of this reaction). The resulting alkene is epoxidized, and the epoxide is reduced. A rearrangement is done at this point. The reaction is similar to that used in Scheme 13.37, except that it involves a saturated, rather than allylic, system. The final steps in the synthesis are those used in Schemes 13.33 and 13.34. 

The reactions of unsymmetrical allylic Grignard reagents such as (42) with epoxides have recently been studied. The products are 5,e-unsaturated alcohols, and normally the reaction occurs at the internal (y-) carbon of the allyl system to give (43) (Scheme 25), but the addition of Cu iodide reverses this regioselectivity to give the a-product (44). 

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

In 1980, Katsuki and Sharpless communicated that the epoxidation of a variety of allylic alcohols was achieved in exceptionally high enantioselectivity with a catalyst derived from titanium(IV) isopropoxide and chiral diethyl tartrate. This seminal contribution described an asymmetric catalytic system that not only provided the product epoxide in remarkable enantioselectivity, but showed the immediate generality of the reaction by examining 5 of the 8 possible substitution patterns of allylic alcohols all of which were epoxidized in >90% ee. Shortly thereafter. Sharpless and others began to illustrate the... 

The reason for the efficient epoxidation of explicitly allylic alcohols with this system can be found in the strong associative interactions occurring between the substrate and the catalyst. The [Ti(tartrate)(OR)2]2 dimer 1, which is considered to be the active catalyst in the reaction, will generate structure 2 after the addition of... 

One problem associated with the peroxotungstate-catalyzed epoxidation system described above is the separation of the catalyst after the completed reaction. To overcome this obstacle, efforts to prepare heterogeneous tungstate catalysts have been conducted. De Vos and coworkers employed W catalysts derived from sodium tungstate and layered double hydroxides (LDH - coprecipitated MgCU, AICI3, and NaOH) for the epoxidation of simple olefins and allyl alcohols with... 

Similarly, efficient tetracyclization (MeAlCl2-promoted) of the bis-allylic silane/ bis-epoxide 97 constitutes the key step in the synthesis of (+)-a-onocerin. In this case, because of the presence of the bis-allylic silane group, a double bis-annula-tion occurs, with the formation of the ethylene-bridge linked bis-decalin system present in the target compound (Scheme 8.26) [46],... 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

Optically active allylic alcohols can only be prepared from optically active sulfinyl epoxides when the created double bond is conjugated to an aromatic system. One example is described below29. 

While asymmetric approaches are certainly important, other synthetically significant epoxidation protocols have also been reported. For example, buffered two-phase MCPBA systems are useful for epoxidations in which the alkenes and/or resultant epoxides are acid-sensitive. Bicarbonate works quite well for cinnamate derivatives (e.g., 55) <96SC2235> however, 2,6-di-t-butyl-pyridine was shown to give superior results in the case of certain allyl acetals (e.g., 57) <96SC2875>. 

Scheme 10.1 gives some representative examples of laboratory syntheses involving polyene cyclization. The cyclization in Entry 1 is done in anhydrous formic acid and involves the formation of a symmetric tertiary allylic carbocation. The cyclization forms a six-membered ring by attack at the terminal carbon of the vinyl group. The bicyclic cation is captured as the formate ester. Entry 2 also involves initiation by a symmetric allylic cation. In this case, the triene unit cyclizes to a tricyclic ring system. Entry 3 results in the formation of the steroidal skeleton with termination by capture of the alkynyl group and formation of a ketone. The cyclization in Entry 4 is initiated by epoxide opening. 

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