Esters, allenic

For the isolation of relatively volatile ot-allenic esters such as... 

The acylation of Wittig reagents provides the most convenient means for the preparation of allenes substituted with various electron-withdrawing substituents. The preparation of o-allenic esters has been accomplished by the reaction of resonance-stabilized phosphoranes with isolable ketenes and ketene itself and with acid chlorides in the presence of a second equivalent of the phosphorane. The disadvantages of the first method are the necessity of preparing the ketene and the fact that the highly reactive mono-substituted ketenes evidently cannot be used. The second method fails when the a-carbon... 

The submitters have shown that these reactions proceed by dehydro-chlorination of the acid chloride to the ketene, which is then trapped by reaction with the phosphorane. The resulting betaine decomposes to the allenic ester via an oxaphosphetane. In contrast, the reaction of acid chlorides with 2 equivalents of phosphoranes involves initial acylation of the phosphorane followed by proton elimination from the phosphonium salt. ... 

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

Under the same reaction conditions, -keto esters which have been alkylated on the a-carbon atom (thus leading to 3,4-disubstituted 5-pyrazolones upon treatment with hydrazine) give allenic esters in good (50-70%) yield (158). The mechanism (Scheme 36) again appears to involve thallation of the enamine tautomer of the 5 -pyrazolone, but deprotonation now takes place... 

A full account has appeared of the reactions of the ester phosphoranes (30 R = H) with acyl chlorides. Equimolecular proportions gave the salts (31) from which /8-ketoesters were obtained on electrolytic reduction. A 2 1 excess of phosphorane gave the allenic esters (32), presumably via the betaines (33). 

Scheme 35 Cu-catalyzed asymmetric reaction of acrylates and allenic esters to ketones...

Reaction of the nitrone 4-184 with allenic esters 4-185 as described by Ishar and coworkers led to the benzo[b]indolizines 4-186, together with small quantities of 4-187 (<5%) (Scheme 4.40) [63]. The first transformation is a 1,3-dipolar cycloaddition this is followed by four further steps, including a [4+2] cycloaddition of an intermediate 1-aza-l,3-butadiene. 

Clavepictines A and B (210 and 211, respectively) were obtained from the allenic ester 227. The reduction of its ester group to aldehyde, followed of addition to the latter of hexylmagnesium bromide, OH protection, and N-deprotection gave compound 228. A silver(i)-mediated cyclization of this compound afforded quinolizidine 229 and its C-6 epimer in a 7 1 ratio (Scheme 44). The former compound was readily converted into the target alkaloids <1997JOC4550>. 

Scheme 2.22 Synthesis of/ -allenic esters 65 by 1,6-cuprate addition to 2-en-4-ynoates 64 and regioselective enolate protonation.

Scheme 4.36 Asymmetric total synthesis of (-)-kallolide B via allenic esters 135 and 136.

The enantioselective synthesis of an allenic ester using chiral proton sources was performed by dynamic kinetic protonation of racemic allenylsamarium(III) species 237 and 238, which were derived from propargylic phosphate 236 by the metalation (Scheme 4.61) [97]. Protonation with (R,R)-(+)-hydrobcnzoin and R-(-)-pantolactone provided an allenic ester 239 with high enantiomeric purity. The selective protonation with (R,R)-(+)-hydrobenzoin giving R-(-)-allcnic ester 239 is in agreement with the... 

There is not just one predominating method for the generation of alienes with at least one electron-withdrawing group, but a number of important routes. Even for the synthesis of alienes with a given acceptor function, for example allenic esters, different routes are often used such as the Wittig reaction, prototropic isomerization or alkoxycarbonylation. 

The photochemical reaction of diiron //-alkcnylidc complexes with diazo compounds leads to -allene complexes, which can be cleaved by several methods to yield allenes, for example allenic esters [32]. 

The photolysis of the furan derivatives 78 yielded the butadienals 79 as the main products [123], Further isomerizations leading to allenic esters used the radiation of a cyclopropene-1 -carboxylic acid ester [124] or applied flash vacuum pyrolysis to 3 -ethoxy cyclobut- 2-en-l-one[125]. 

Not least for the syntheses of natural products, alkoxycarbonylations with formation of allenic esters, often starting from mesylates or carbonates of type 89, are of great importance [35, 137]. In the case of carbonates, the formation of the products 96 occurs by decarboxylation of 94 to give the intermediates 95 (Scheme 7.14). The mesylates 97 are preferred to the analogous carbonates for the alkoxycarbonylation of optically active propargylic compounds in order to decrease the loss of optical purity in the products 98 [15]. In addition to the simple propargylic compounds of type 89, cyclic carbonates or epoxides such as 99 can also be used [138]. The obtained products 100 contain an additional hydroxy function. 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

The attack of the nucleophile on the acceptor-substituted allene usually happens at the central sp-hybridized carbon atom. This holds true also if no nucleophilic addition but a nucleophilic substitution in terms of an SN2 reaction such as 181 — 182 occurs (Scheme 7.30) [245]. The addition of ethanol to the allene 183 is an exception [157]. In this case, the allene not only bears an acceptor but shows also the substructure of a vinyl ether. A change in the regioselectivity of the addition of nucleophilic compounds NuH to allenic esters can be effected by temporary introduction of a triphenylphosphonium group [246]. For instance, the ester 185 yields the phos-phonium salt 186, which may be converted further to the ether 187. Evidently, the triphenylphosphonium group induces an electrophilic character at the terminal carbon atom of 186 and this is used to produce 187, which is formally an abnormal product of the addition of methanol to the allene 185. This method of umpolung is also applicable to nucleophilic addition reactions to allenyl ketones in a modified procedure [246, 247]. 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

Finally, the attack of a nucleophile can fail to occur both on the electron-deficient allene and on the acceptor, and instead of this it can take place at another part of the substrate. For example, the allenic esters 195 yield products of type 196 by addition of different nucleophiles at the more reactive isocyanato group [120]. 

However, an existing nucleophile can also cause the ring closure after building up the electron-deficient allene. By methoxycarbonylation (cf. Section 7.2.6) of ethy-nyloxiranes 200, the allenic esters 201 are formed first, which react immediately to give the heterocycles 202 or 203, depending on the substitution pattern of the starting material [138]. 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

By treatment of allenic esters with N-benzylideneaniline and boron trifluoride, ring dosures to but-2-enolides with introduction of a carbon substituent at position 3 are also possible [306], However, both the number of examples and the yields are low. 

Some cases are known in which Diels-Alder reactions of electron-deficient allenes and dienes compete with [2 + 2]-cycloadditions (see also Section 7.3.7) [12, 151, 335, 336]. Recently, a phosphane-catalyzed [4 + 2]-annulation starting from allenic ester 337 and N-tosylaldimines 338 was published [337]. However, the formation of the tetrahydropyridines 339 isolated in excellent yields is explained by a multi-step mechanism and only resembles a Diels-Alder reaction. 

Allenic esters such as 349 [12] or allenyl ketones such as 351 [42] are able to undergo intramolecular [4+2]-cycloadditions with participation of both the inactivated or the activated C=C bond of the allene, respectively. The latter starting material is consumed at room temperature, yielding only one product. However, similar... 

Allenic esters such as 185 can act not only as dipolarophiles but also, at least formally, as 1,3-dipoles, which was shown by Xu and Lu during the phosphane-cata-lyzed reaction with N-tosylimines 387 (Scheme 7.52) [358, 359]. The heterocycles 388 are formed at least in moderate and mostly in excellent yields, if R1 is an aryl or a vinyl group. The formation of the products can be explained by reversible nucleophilic addition of the phosphane to 185 (cf. Section 7.3.1) followed by nucleophilic addition of the resulting intermediate to the imine 387. 

Allenic esters can be generated by palladium-catalyzed carbonylation of propargyl compounds (see Section 7.2.6). Under the reaction conditions applied, however, succeeding reactions occur directly in many cases, for instance by introduction of a second ester function. Many examples of such carbonylation reactions of allenic esters were summarized in a review by Tsuji and Mandai [136],... 

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