Allenes, electron-deficient

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

The reactions of acceptor-substituted allenes are as manifold as their syntheses. The electron deficiency of the inner C=C double bond prove to be the predominating property of these allenes. Therefore, nucleophilic addition at the central carbon atom is an important first step inducing many reactions of the electron-deficient allenes. 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

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]. 

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. 

Allenes as versatile synthons including Diels-Alder reactions and especially intramolecular cycloadditions of this type were reviewed by Aso and Kanematsu [338], In some cases of intramolecular Diels-Alder reactions of open-chain starting materials such as 340 [339], 342 [339] and similar acceptor-substituted allenes [156], the formation of two new six-membered rings seems to be favorable if possible (Scheme 7.48). The non-activated cumulated C=C bond of 340 takes part in the [4+ 2]-cycloaddition and hence the necessary reaction temperature is high. On the other hand, the progressive truncation of the tether and the electron deficiency of the allenic C=C bond involved give rise to a remarkable Diels-Alder reactivity of the sulfone 346 generated in situ from sulfoxide 345 [339]. 

Dipolar cycloadditions to electron-deficient allenes are not regioselective, taking place at the electron-poor C=C bond, in all cases. For example, the reaction of 372 with nitrile oxide 378 furnishes a mixture of products 379-383 [356], Obviously, 379, 380 and 381 result from different [2 + 3]-cycloadditions followed by tautomer-ism, whereas 382 and 383 are formed from the primary products of the 1,3-dipolar cydoaddition via addition of a second equivalent of 378 to the remaining exocyclic C—C bond. 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

AUenyl pyridinium salts 303 are a class of electron-deficient allenes, of which the center carbon atom can accept nucleophilic addition of diethylamine and pyridine derivatives [147, 148]. 

Electron-deficient olefins such as acrylonitrile can participate in the cross [2 + 21-cycloaddition with allenes. 3-Methylenecydobutanecarbonitrile (17) was obtained in 60% yield by the reaction of allene with a large excess of acrylonitrile under autogenous pressure at 200 °C [16]. Initial bond formation takes place between the central carbon of allene and the terminal carbon of acrylonitrile to give a diradical species, which cydizes to form the cydoadduct [17]. 

Cydoaddition reactions of electron-deficient allenes are also known. In the presence of A1C13, ethyl 2,3-butadienoate (32) reacts with alkenes to give cyclobutyl-ideneacetic esters at room temperature [28]. 

The facile [2 + 2]-cycloaddition took place at lower temperatures with a combination of an allene and an alkyne of opposite electronic bias [65], An electron-rich allene 59 reacted with an electron-deficient alkyne to give a [2 + 2]-cydoadduct in good yield [59a]. 

Allenes participate in the Diels-Alder-type [4+2]-cycloaddition mostly as an electron-deficient dienophile. The LUMO energy level of an allene is lowered by the introduction of an electron-withdrawing unsaturated substituent. The largest LUMO coefficient locates on the central carbon (C2) and the next largest on the substituted carbon (Cl). Thus, [4 + 2]-cycloadditions of activated allenes take place at the internal C=C bond of the allene. 

Electron-deficient allenes also undergo hetero-Diels-Alder reactions. N,N-Dimethyl-hydrazones 193 reacted with allenedicarboxylate 110a in refluxing acetonitrile to give 2-carboxy-3-pyridineacetic acid diesters [157]. 

Butenolides can he produced after cathodic reduction involving an electron-deficient allene and a ketone (Scheme 72) [105]. 

When cyclization occurs between an electron-deficient allene and a ketone, as is the case with 27, butenolides are produced [19]. Given the importance of this functional group in cardiac glycoside natural products, the simplicity of the starting materials, and the facility of the cathodic cyclization, it may be worth noting the opportunity to utilize this transformation in the construction of these natural products. 

The potential carbodicarbene C(C(NMe2)2 2 has been known for a long time but no complex has been reported [101, 102]. It adopts a linear allene geometry in the free state but according to theoretical analysis exhibits a strong nucleophilic central carbon atom [4, 97] and can be seen as an allene with a hidden divalent carbon(O) character emerging in the presence of electron deficient electrophiles. Based on these findings a new field of chemistry will be opened and the number of compounds with a coordination mode should increase in the future. 

The procedure described here serves to illustrate a general [3+2] annulation method for the synthesis of cyclopentane derivatives. A unique feature of this one-step annulation is its capacity to generate regio-specifically five-raembered rings substituted at each position, functionally equipped for further synthetic elaboration. As formulated in the following equation, the reaction proceeds with remarkably high stereoselectivity via the effective suprafacial addition of the three-carbon allene component to an electron-deficient olefin ("allenophile"). ... 

Nucleophilic allenes react readily with electron-deficient alkenes giving cyclobutanes. Thus, instant cycloaddition occurs between methoxyallene (26) and 2-[bis(trifluoromethyl)methylene]-propanedinitrile.21... 

Triphenylphosphine was employed as a nucleophilic catalyst for the umpolung addition of azoles (225) to the electron-deficient allenes (226 R1 = H, R2 = OEt, R3 = H, Et) to afford the addition products (227). This organocatalytic methodology has been extended to addition-cyclization reactions between electron-deficient allenes or alkynes and pyrrole-2-carboxaldehyde in the presence of a catalytic amount of tri-butylphosphine, giving the substituted indolizine-7-carboxylates (228 R2 = OEt, Me R3 = H, Et).265... 

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

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