Vinyl, with epoxides

An alternate way to make block copolymers involving PDMS blocks 124,125) is to have these chains fitted with epoxide functions at chain end, and to react them with a vinylic or dienic polymer carrying terminal COOH functions. Sequential addition of monomers has also been used, the ring opening polymerization of the cyclic trimer (D3) being initiated by the anionic site of a living polymer126). 

Bogy o s group developed several ABPs for cysteine proteases with epoxide, vinyl sulfone, and acyloxymethyl ketone reactive groups [42,43]. Particularly noteworthy is DCG04 (4), a biotinylated papain-family protease inhibitor with an epoxide reactive group that targets... 

Scheme 57 illustrates an example of this process coupling of the lithio reagent derived from vinyl stannane 237 with epoxide 242 leads to the C-disaccharide derivative 243 in good yield. A double transmetallation to give an organocopper reagent 244 can facilitate the C-glycosylation reaction with allyl halides [80] (Scheme 58). 

Spiro epoxidation of a -enones.1 The conversion of ketones to spiro epoxides is usually carried out with dimethylsulfonium methylide, but this reaction can proceed in low and variable yields when extended to a,p-enones. A generally useful route to these vinyl spiro epoxides involves addition of 1, methylation, and ring closure with base, as illustrated for cyclohexenone. 

The solution thus consists of different particles denoted as contact ion pairs, solvent-separated ion pairs and free ions. The fraction of the individual particles depends on the type of salt, type of solvent, polymerization system, temperature, and salt concentration. The catalytic effect of these particles may be very different as is evident in anionic polymerization of vinyl monomers. For instance, free polystyryl anion is 800times more reactive than its ion pair with the sodium counterion 60 . From this fact it follows that, although the portion of free ions is small in the reaction system, they may play an important role. On the other hand, anionic polymerization and copolymerization of heterocycles proceeds mostly via ion pairs. This is due to a strong localization of the negative charge on the chain-end heteroatom which strongly stabilizes the ion pair itself62. Ionic dissociation constants and ion contributions to the reaction kinetics are usually low. This means that for heterocycles the difference between the catalytic effect of ion pairs and free ions is much weaker than for the polymerization of unsaturated compounds. This is well documented by the copolymerization of anhydrides with epoxides where the substi-... 

The palladium-catalyzed fixation of C02 is also a useful method for the synthesis of CCs, with the first such example using vinyl-substituted epoxides and a palladium catalyst [Pd(PPh3)4/PPh3] having been reported independently by both Fujinami and Trost [147, 148]. Here, the carbonate is produced via the formation of a first tr-allyl-palladium intermediate (I) this then fixes C02 to form a second tr-allyl-intermediate (II) that produces vinyl-substituted cyclic carbonates (Scheme 7.8). 

Allylboration of representative vinylic epoxides with allylboranes afforded a mixture of 1,2- and 1,4-addition products with epoxide ring opening. In contrast, 3,4-epoxycyclopentenes (R = H, Me) unexpectedly resulted in opening the five-membered ring (Equation (147)).613... 

The (Z)-vinylic cyanocuprates also react with epoxides (e.g., 198) giving the (Z)-homoallylic alcohols (e.g., 199).41,270 The reaction is stereospecific and offers the possibility of its application in enantioselective synthesis (Scheme 109). 

Aryl borates can provide both C-alkylation and O-alkylation products upon reaction with epoxides <07JOC7761>. The reaction shown below exemplifies a general reaction of arylborates with vinyl epoxides <07SL3011>. A number of examples were reported, the yield shown is typical. The ratio of SN2 to SN2 is generally >95 5 and the ratio of C-alkylation O-alkylation is also excellent (usually >95 5). 

Cyclization of vinyl ether epoxides, Epoxy dihydropyranes undergo cyclization in the presence of Lewis acids. Thus treatment of 1 with basic alumina affords 2 in almost quantitative yield. The product can be converted into the keto aldehyde 5 by treatment with a mineral acid followed by oxidation. Another useful reaction of 2 is conversion to the keto lactone 3 by singlet oxygen. 

Substituted phenethyl isocyanates undergo cyclization to lactams when treated with BF3 Et20 [65]. Vinyl ether epoxides (Eq. 37) [66], vinyl aldehydes [67], and epoxyjS-keto esters [68] all undergo cyclization with BF3 Et20. 

Scheme 3.23. Cydobutere ard alkylidine cyclobutare synthesis by starrylcupratior of alkyres ard trapping of the resultant vinyl cuprate with epoxides [15 c].

Other promising methods for the stereoselective introduction of the vinyl moiety into functionalized organic substrates are the reactions of such adducts with epoxides to produce homoallylic alcohols (equation 70) ° and with conjugated enones to yield ketones (equation 71). 58.i59 gQtj, reactions have major limitations, and their application in a special instance may require a study of the effect of Lewis acids or transition metals as promoters or selectivity agents. 

N-acylaziridines occurs on treatment with triphenylphosphine with the formation of the ylides (67), thereby providing a route to a-substituted primary allylic amines via their in situ reactions with aldehydes.The reactions of triphenylphosphine with epoxides in phenolic media provide a new access to the vinyl-phosphonium salts (68). A route to 1-hydroxyalkylphosphonium salts is provided by the reactions of trimethyl- or triethyl-phosphine with aldehydes or ketones in the presence of anhydrous acids. The related 1-trimethylsiloxyalkylphosphonium salts can be isolated in the presence of trimethylsilyl chloride.Further Wittig-products have been isolated from the reaction of 1,2,3-indanetrione with triphenylphosphine, and, in related work, it has been shown that furoin is deoxygenated on heating with triphenylphosphine to form 2-furfuryl(2-furyl)ketone and triphenylphosphine oxide.The structure of the blue product from the reaction of triphenylphosphine with 2,3,5,6-tetracyano-7-oxabicyclo(2,2,1]hepta-2,5-diene has now been shown by X-ray techniques to be the stable ylide (69). ... 

Remaricable diastereocontrol was also reported by Trost during alkylation of allylic sulfones with epoxide. A very high kinetic diastereoselectivity was observed in the case of terminal epoxide and branching on the vinyl carbon proximal to sulfone (Scheme 83). 

We selected the natural product thyrsiferol as an ideal target to test our ideas. Its total synthesis was envisioned to proceed as illustrated in the Scheme 28. The successful coupling between aldehyde 84 and vinyl iodide 82 via a Nozaki-Hiyama-Kishi (NHK) reaction [66] had been demonstrated previously [29]. We therefore sought to model our final steps after precedence presented by Forsyth for the union of these two fragments. The focus of our synthetic strategy centered around the stereoselective synthesis of the ABC framework (84) of thyrsiferol (1) as a scaffold to validate the scope of the Cp2TiCl reaction with epoxides toward the assembly of Q-C-glycosides and cyclic ethers. 

On the other hand, doubly metallated 2-propanethiol (thioacrolein dianion) reacts preferentially (7 0 ratio = 70 30, Scheme 16, entries b and d) at its -position - with alkyl and benzyl chlorides and bromides and with epoxides. The cis stereochemistry found in the 7-adduct suggests that the organometallic is internally chelated as shown in Scheme 16. The nature of the metal (Li or K) does not affect the percentages of the alkylated vinyl sulfides,whereas addition of HMPA to the dilithio derivative inverts the regioisomeric ratio obtained (Scheme 16, entry c, compare to entries b and d). ... 

The related (Z)-lithium dialkenylcuprates (147) derived from acetylene itself also react well with epoxides to provide a useful route to (2)-homoallylic alcohols the lack of reactivity with esters allows an easy access to lactones (148) by condensations between epoxy esters and this type of cuprate (Scheme 29). Likewise, the lower homologs (149) and (151), both of which are relatively easy to prepare in optically active forms, can be readily converted into homoallylic and bishomoallylic alcohols (150) and (152) respectively. An ester unit can also be incorporated into the cuprate functions thus, addition of a mixed lithium cuprate, RCuYLi , to ethyl propiolate gives the cuprates (153), which add to epoxides to give unexpectedly the (Z)-crotonates (154). Such isomerization is not uncommon with vinyl carbanions in general, and is obviously a limitation when isomeric mixtures are produced. 

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