Epoxide synthetic equivalent

The synthon will be, in a lower valeney state - if X is C then it will be a carbene or the synthetic equivalent of a carbene. Let s see how this disconnection works out for epoxides. Taking X = O first we have... 

Vinylic sulfides containing an a hydrogen can also be alkylated by alkyl halides or epoxides. This is a method for converting an alkyl halide RX to an a,P unsaturated aldehyde, which is the synthetic equivalent of the unknown HC=CH—CHO ion. Even simple alkyl aryl sulfides RCH2SAr and RR CHSAr have been alkylated a to the sulfur. ... 

Although the Sharpless asymmetric epoxidation is an elegant method to introduce a specific defined chirality in epoxy alcohols and thus, in functionalized aziridines (see Sect. 2.1), it is restricted to the use of allylic alcohols as the starting materials. To overcome this limitation, cyclic sulfites and sulfates derived from enantiopure vfc-diols can be used as synthetic equivalents of epoxides (Scheme 5) [12,13]. 

The reductive elimination of a variety of )3-substituted sulfones for the preparation of di-and tri-substituted olefins (e.g. 75 to 76) and the use of allyl sulfones as synthetic equivalents of the allyl dianion CH=CH—CHj , has prompted considerable interest in the [1,3]rearrangements of allylic sulfones ". Kocienski has thus reported that while epoxidation of allylic sulfone 74 with MCPBA in CH2CI2 at room temperature afforded the expected product 75, epoxidation in the presence of two equivalents of NaHCOj afforded the isomeric j ,y-epoxysulfone 77. Similar results were obtained with other a-mono- or di-substituted sulfones. On the other hand, the reaction of y-substituted allylic sulfones results in the isomerization of the double bond, only. The following addition-elimination free radical chain mechanism has been suggested (equations 45, 46). In a closely related and simultaneously published investigation, Whitham and coworkers reported the 1,3-rearrangement of a number of acyclic and cyclic allylic p-tolyl sulfones on treatment with either benzoyl peroxide in CCI4 under reflux or with... 

The synthetic equivalents of the carbocations can be, of course a carbonyl group or a carbon with a leaving group -X, an epoxide or an activated double bound. 

The most widely used method for the preparation of 1,3,2-dioxathiolane. Y-oxides (cyclic sulfites) 65 bearing C-linked substituents is the reaction of the corresponding 1,2-diols with thionyl chloride in presence of pyridine or Et3N (Scheme 18). More reactive 1,3,2-dioxathiolane. Y,.Y-dioxidcs (cyclic sulfates) 66 are usually obtained by oxidation of sulfites 65 with sodium periodate, which is mediated by mthenium tetroxide generated in situ from a catalytic amount of ruthenium trichloride. Numerous derivatives 65 and 66 were obtained via this approach and its modifications for further transformations, mostly as the synthetic equivalents of epoxides <1997AHC89, 2000T7051> (see also Sections 6.05.5 and 6.05.6, and Tables 1-7). 

Dioxathiolane. Y-oxidcs (cyclic sulfites) and 1,3,2-dioxathiolane. Y,.Y-dioxides (cyclic sulfates) have been widely used in organic chemistry, mostly as the synthetic equivalents of epoxides (Sections 6.05.5 and 6.05.6 Tables 1-7). 

Heterocycles of this type occur widely. The benzo[l,3]dioxole ring system is often found in natural products and their degradation products, e.g., sesamol 38 lipoic acid 39 is a naturally occurring 1,2-dithiolane derivative. The 1,3-dithiolanes 40 are commonly known as 1,3-dithioacetals and have been extensively used in carbonyl group chemistry. In the absence of cyclic conjugation, ring sulfur atoms can readily exist in higher oxidation states as, for example, in the oxathiole S, -dioxide 41. 1,3,2-Dioxathiolane A-oxides 42 (cyclic sulfites) and 1,3,2-dioxathiolane A,A-dioxides (cyclic sulfates) are useful as synthetic equivalents of epoxides. 

Table 8. Optimum Reported Diastereoselectivities in the Epoxidation of Simple Acyclic Allylic Alcohols and Their Silylated Synthetic Equivalents...

In 1985, we reported that reduction of a prochiral 1,3-diketone A (Figure 3.6) with fermenting baker s yeast (Saccharomyces cerevisiae) was enantioselective to give (5)-hydroxy ketone B of 98-99% ee.26 I noticed that the Baeyer-Villiger oxidation of B would furnish (S)-hydroxylactone, a building block synthetically equivalent to the terminal epoxide moiety of (+)-JH III. This idea was used for the synthesis of (+)- and (-)-JH III in 1987.27... 

The bisadduct 87, synthesized from anthracene bis-(l,4-epoxide) (88) and tetraphenylcyclone (89), is a synthetic equivalent of the [l,2-c 4,5-c ]benzodi-furan 90 (R=H). Adduct 87 reacts thermally with dienophiles including some exceedingly weak ones to give linear acene derivatives in moderate to very good yields (see Scheme 44 [142b]). 

Sharpless and Kim reported a one-pot synthesis of cyclic sulfates 96 from 1,2-diols via catalytic oxidation with ruthenium chloride51. The cyclic sulfates 96 thus formed on treatment with nucleophiles give /2-sulfates 97, which in turn are hydrolyzed to the / -hydroxy compounds 98 (equation 54). Hence the cyclic sulfates 96 are synthetically equivalent to epoxides. The results of ring opening of cyclic sulfates 96 are shown in Table 4. When the reaction of 99 with malonate anion is carried out in DME, the /2-sulfate moiety serves as a leaving group to give cyclopropane 100 (equation 55)51. 

An approach to the 1,3-polyol system complementary to that shown in Schemes 83 and 84 makes use of dithiane 598 as a synthetic equivalent of 603. Alkylation of the anion generated from 598 with epoxide 303 gives the coupled dithiane 599. After hydrolysis of the thioacetal, a 57 -selective reduction of ketone 600 with lithium aluminum hydride in the presence... 

The cyclic sulfites or sulfates thus obtained can be employed as synthetic equivalents of epoxides, which can react with a number of nucleophiles often, they are more reactive than the oxirane analogs and thus can lead to disubstitution products <1997AHC89, 1994CRV2483>. The cyclic sulfate 42, for example, has been used as a double electrophile in a [3+3] annulation procedure, which combines C-C-C and N-C-C moieties (Scheme 14)... 

The strategy for the synthesis of functionalised epoxides involved the oxidation of ( )-olefinic precursors resulting from the Wittig coupling of aldehydes 287 with the appropriate phosphoranes [125]. The treatment of the phosphonium salt 295 [158], a synthetic equivalent of the p-propionate unit, with n-butyllith-ium gave the corresponding ylide which was reacted in situ with aldehydes 287 (Scheme 89). The Wittig reaction was stereoselective in favour of the desired trans olefin 296 (E Z = 9 1). A conventional two step procedure [158] allowed the formation of carboxylic acids 297 from trimethylsilylalkyne precursors. The oxidation step led to intractable mixtures. Apparently the epoxides 298 were unstable under these conditions. 

C-C P is an epoxide. Given these synthetic equivalents and the need to disconnect carbon-carbon bonds near the functional group, a real example will illustrate the protocol. 

Several possible disconnections are now possible based on the C-0 bond polarization, and one is cleavage of bond f, which leads to 44 and 45. This was chosen because Table 25.1 contains the a pt rC-C-0 fragment that correlates with an epoxide. This correlates with acceptor fragment 45, which has epoxide 47 as a synthetic equivalent. If 45 is the acceptor fragment, then 44 is the donor, which correlates with the Grignard reagent derived from halide 46. Halide 46 does not fit the criterion for a starting material because it has too many carbon atoms. 

The above scheme presents disconnections of oxiranes (epoxides), aziridines and thiiranes (thioepoxides) leading to six-electron synthons and their synthetic equivalents. 

In Sect. 5.2.2, Example 5.12, we saw the electrophilic character of epoxide toward the alkoxide ion. The carbanion is another charged nucleophile that opens a three-membered ring in reaction with epoxides. When such an anion is unstabilized, its synthetic equivalent is an organometallic compound affording a-alkylated or arylated alcohols as products (Scheme 5.50a). 

On the other hand, if the compound is disconnected at bond b, then we see that an epoxide is the synthetic equivalent for the electrophile and an organocuprate is the synthetic equivalent for the nucleophile. 

Vinylsilanes derived from ketones (generation of vinyl anion by Shapiro reaction) are converted by epoxidation and reduction into j8-hydroxyalkylsilanes, which on oxidation with H2Cr04 give the 1,2-transposed ketones. /8-SiIyl-ketones can be considered synthetically equivalent to masked a,/8-enones, as exemplified in Scheme 14. " Silyl anions also undergo conjugate addition to... 

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