E Unsaturated Esters

The reaction of ozone with vinyl acetate has been studied by Grosjean and Grosjean (1998) by monitoring the rate of decay of vinyl acetate when exposed to a large excess of ozone in 1 atm. of air at 291-292 K. A rate coefficient of k[03 CH2=CH0C(0)CH3] = (3.20 0.47) X 10 cm molecule s was derived. 

Combining the rate coefficients for reaction with OH radicals and O3 with a daytime average [OH] = 2.5 x 10 and a diurnal average [O3] = 10 molecule cm gives estimates of about 4 h for the daytime atmospheric lifetime of vinyl acetate with respect to reaction with OH radicals and about 4 days with respect to reaction with O3. Reaction with OH radicals is an important atmospheric fate of vinyl acetate and is expected to proceed via addition to the double bond leading to the formation of CH2O and 

The kinetics of the reaction of OH radicals with allyl acetate have been studied by Ferrari et al. (1996) using relative rate methods and Le Calvd et al. (2000) 

Le Calve et al. (2000) used relative rate methods to determine the reactivity of allyl acetate relative to methyl vinyl ketone (MVK). Scaling the results from Le Calvd et al. (2000) to our recommended value of kiOs MVK) = 5.0 x 10 gives (03 allyl acetate) = (2.5 0.7) x 10 cm molecule s at 298 K. 

Combining the recommended rate coefficients for reactions with OH radicals and O3 with a daytime average [OH] = 2.5 x 10 molecule cm and a diurnal average [O3] 10 molecule cm gives estimates of about 4 h and about 5 days for the 

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Triethyl phosphonoacetate, 322 7,8-Unsaturated esters Ethyl 3,3-diethoxyacrylate, 131 8,e-Unsaturated esters Allyltrimethylsilane, 11 Dienals... 

In practice he used the E-unsaturated ester 71, as that was easier to make, and added isopropyl Grignard with a CuSPh catalyst (see compound 13 above) to avoid wasting one equivalent of the Grignard. The ester product 72 cyclised to the target with polyphosphoric acid without a specific ester hydrolysis step. No doubt this works so well because it is an intramolecular reaction giving a five-membered ring. 

The synthetic attractant siglure 15 used as bait for the Mediterranean fruit fly has all the features of a Diels-Alder adduct and we need the E-unsaturated ester 16 for the reaction.5... 

Additions to activated triple bonds,14 like ethyl propiolate, provide a simple entry to (E)-unsaturated esters. In the presence of TMSC1, incorporation of the TMS group in the product is observed (Scheme 10.6).19... 

Lactonization of a h>e-unsaturated ester In a projected synthesis of quassinoid diterpenes, the final step involves lactonization of the unsaturated ester 1. Acid-catalyzed solvolysis (HC1 in THF) or treatment with an arylsulfonic acid in toluene results mainly... 

Two types of cyclization reaction take place when a ketene silyl acetal is treated with a carbenoid generated from CHBrs and ZnEt2. ° When the substrate is aliphatic (Scheme 7), a cyclopropylcarboxy-late is formed due to a CH insertion reaction of an intermediate zinc carbenoid. With substrates having an alkene in the vicinity of the carbenoid (Scheme 7), in particular those derived from 8,e-unsaturated esters, internal cyclopropanation takes place. 

Another use of 1 (n = 3) is the coupling with vinyl iodides or triflates, which furnish S.e-unsaturated esters. One example is shown in eq 5, The reaction proceeds with retention of the double bond geometry. 

An equivalent of a homologous Claisen ester enolate rearrangement leading to 6,e-unsaturated esters has as its key step a Cope rearrangement of readily prepared, unsaturated O-trimethylsilyl cyanohydrins (Scheme 25). The overall process looks to be very efficient, the one drawback being the time and temperature requirements for the rearrangement (e.g. 195 C, 22 h). 

Mitsubishi (U.S. Patent 4,020,264) modified AA-TiCl3 by ball-milling 0.3 g. with 3-5 ml of a,e-unsaturated esters for 8 to 16 hrs. to increase the stereospecificity but at the expense of some loss of activity as shown in Table III. 

Aryl and vinylic bromides and iodides react with the least substituted and most electrophilic carbon atoms of activated olefins, e.g., styrenes, allylic alcohols, a,p-unsaturated esters and nitriles. 

A related reaction is the acylation of yA disuhstituted benzyl ketones to isobenzopyrylium salts the unsubstituted compounds yield 4-pyrones as shown in Section II,D,3,a. Another related acylation converts unsaturated esters into 2-p3U ones, e.g., ethyl, jS-dimethyl-acrylate into 4,6-dimethyl-2-pyrone. ... 

Among the most successful classes of asymmetric acyl anion equivalents are the dioxane-containing a-amino nitriles 99 introduced by Enders and coworkers. These are deprotonated by EDA, and the resulting anions act as efficient equivalents of RCO for addition to a, (3-unsaturated esters [90AG(E)179],... 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

The first examples of Horner-Wadsworth-Emmons reactions have been reported by Kitazume and Tanaka [60]. Here the ionic liquid [EDBU][OTf] was used in the synthesis of a-fluoro-a,P-unsaturated esters (Scheme 5.1-32). It was found that when K2CO3 was used as a base, the E isomer was the major product and that when DBU was used as a base, the Z isomer was the major product. The reaction was also performed in [EMIM][BF4] and [EMIM][PFgj, but gave lower yields than with [EDBU][OTf] [60]. 

Because the olefin geometry in compound 9 will most certainly have a bearing on the stereochemical outcome of the hydroboration step, a reliable process for the construction of the trans trisubsti-tuted olefin in 9 must be identified. A priori, the powerful and predictable Wittig reaction28 could be used to construct E u, [3-unsaturated ester 10 from aldehyde 11. Reduction of the ethoxycarbonyl grouping in 10, followed by benzylation of the resulting primary alcohol, would then complete the synthesis of 9. Aldehyde 11 is a known substance that can be prepared from 2-furylacetonitrile (12). 

Although the methodology described so far produces <5-oxo esters via diastereoselective enolate additions to enones, the same product may be obtained via an alternate sequence, i.e., addition of ketone or aldehyde enolates to a,j3-unsaturated esters or amides. Enolates of ketones are known to react with a,/ -unsaturated esters to give the Michael adducts50, however, the study of simple diastcrcoselectivity has, so far, been limited to special cases (MIMIRC reactions, Section 1.5.2.4.4.). 

The intramolecular Michael addition of acyclic systems is often hampered by competing reactions, i.e., aldol condensations. With the proper choice of Michael donor and acceptor, the intramolecular addition provides a route to tram-substituted cyclopentanones, and cyclopentane and cyclohexane derivatives. Representative examples are the cyclizations of /3-oxo ester substituted enones and a,/J-unsaturated esters. 

A related stereoselective route to glutamic acid derivatives consists of the addition of the nickel complex 5 to various activated olefins, i.e., 2-propenonitrile, 2-propenal and a,/ -unsaturated esters. 

A different task was pursued by the CM of CsA with various maleates 339 [ 148]. The CM demanded in this case the highly active Hoveyda catalyst D, that exhibits potency not reached by the phosphine-containing catalysts C and E. Under the conditions given in Scheme 65, metathesis with maleates 339 led (E)-selectively to the a,/J-unsaturated ester derivatives 340 in high yield. Compounds 340 still demonstrated activity comparable to that of CsA and are thus potential soft drugs via esterase-mediated biotransformation to the corresponding inactive carboxylic acids 341. 

Thus unsubstituted (R=H) and substituted (R = alkyl) non-stabilized diyiides 1 react with phenylisocyanate and dicyclohexylcarbodiimide (R NCX), leading to the formation of new monoylide type intermediates. These last ones react in situ with carbonyl compounds through a Wittig type reaction leading respectively to a,)8-unsaturated amides 2 and amidines 3, with a high E stereoselectivity, the double bond being di- or tri-substituted [48,49]. By a similar reactional pathway, diyiides also react with carbonic acid derivatives, with the synthesis as final products of -a,/l-unsaturated esters 4 and acids 5 [50]. 

Table 3 summarizes the scope and limitation of substrates for this hydrogenation. Complex 5 acts as a highly effective catalyst for functionalized olefins with unprotected amines (the order of activity tertiary > secondary primary), ethers, esters, fluorinated aryl groups, and others [27, 30]. However, in contrast to the reduction of a,p-unsaturated esters decomposition of 5 was observed when a,p-unsaturated ketones (e.g., trans-chalcone, trans-4-hexen-3-one, tra s-4-phenyl-3-buten-2-one, 2-cyclohexanone, carvone) were used (Fig. 3) [30],... 

Reactions with phosphonoacetate esters are used frequently to prepare ,[ -unsaturated esters. This reaction is known as the Wadsworth-Emmons reaction and usually leads to the E-isomer. 

The diastereoselective ultrasonically induced zinc-copper 1,4-addition of alkyl iodides to chiral a, (i-unsaturaied systems in aqueous media was studied by Suares and co-workers the Z-isomer gives good diastereos-electivities while reactions with the E-isomer are nonstereoselective.63 The 1,4-addition to chiral y, a-dioxolanyl-a, (i-unsaturated esters also proceeds with good yields (51-99%) (Eq.10.29).64... 

Rando and von E. Doering have investigated the synthetic utility of double bond positional isomerization in the photolysis of a,j8-unsaturated esters,<106)... 

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