Allenes, cycloaddition with

The study of the intramolecular nitrile oxide—allene cycloaddition shows, in particular, that dehydration of nitroallene 339 by PhNCO, generates a nitrile oxide in situ, which gives isoxazoline 340 (Scheme 1.36). Thus, the reaction of the more remote double bond with the formation of six-membered ring prevails (405). 

Vinyl Fischer carbenes can be used as three-carbon components in Ni(0)-mediated and Rh(l)-catalyzed [3 + 2 + 21-reactions with alkynes (Schemes 48 and 49)142 and with allenes (Schemes 50 and 51).143 All three of the proposed mechanisms for the [3 + 2 + 2]-cycloadditions involve an initial carbene transfer from chromium to nickel or rhodium (Schemes 49, 52, and 53). As is seen from the products of the two [3 + 2 + 2]-reactions with 1,1-dimethylallene, although the nickel and rhodium carbenes 147G and 147K appear similar, the initial insertion of the allene occurs with opposite regioselectivity. 

Beyond dimerization and oligomerization, [2 + 2]- and [4+ 2]-cycloadditions with conjugated dienes and styrenes and the addition of nucleophiles are typical reactions of strained cyclic allenes. These transformations have been studied most thoroughly with 1,2-cyclohexadiene (6) and its derivatives [1, 2]. Concerning the cycloadditions, a theoretical study had the surprising result that even the [4+ 2]-cycloadditions should proceed in two steps via a diradical intermediate [9]. In the case of nucleophiles, the sites of attack at several 1,2-cyclohexadiene derivatives having an... 

By chance, the existence of the borane complex 330 of 329 was discovered. The liberation of 330 occurred with the best efficiency with sodium bis(trimethylsilyl)-amide from the borane complex 327 of 326. When styrene or furan was used as the solvent, three diastereomeric [2 + 2]-cycloadducts 328 and [4 + 2]-cycloadducts 331, respectively, were obtained in 30and 20% yield (Scheme 6.70) [156]. With no lone pair on the nitrogen atom, 330 cannot be polarized towards a zwitterionic structure, which is why its allene subunit, apart from the inductive effect of the nitrogen atom, resembles that of 1,2-cydohexadiene (6) and hence undergoes cycloaddition with activated alkenes. It is noted that the carbacephalosporin derivative 323 (Scheme 6.69) also does not have a lone pair on the nitrogen atom next to the allene system because of the amide resonance. 

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... 

Saalfrank, Hoffmann and co-workers performed a number of reactions with tetra-alkoxyallenes such as 196 (Scheme 8.47) [1, 41, 105, 114—116] and demonstrated that this class of donor-substituted allenes can serve as a 1,3-dianion equivalent of malonic acid. Treatment of 196 with cyclopropyldicarboxylic acid dichloride 197 produces 2,4-dioxo-3,4-dihydro-2H-pyran 198 through release of two molecules of ethyl chloride [115]. Similarily, the reaction of this allene 196 with oxalyl chloride gives 3-chloromalonic acid anhydride derivative 199. This intermediate is a reactive dieno-phile which accepts 2,3-dimethyl-l,3-butadiene in a subsequent [4+2] cycloaddition to afford cycloadduct 200 in good yield [116]. 

Zecchi and co-workers also reported 1,3-dipolar cycloadditions with nitrogen-substituted allenes. As illustrated in Scheme 8.75, the expected isoxazoline derivatives 285 were obtained by [3 + 2] cycloaddition reaction of aminoallenes 246 and nitrile oxide 284 [141, 142], Bis-adducts 286 became the major products when 2equiv. of nitrile oxide 284 were applied with prolonged reaction times. 

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]. 

Ketene is also a suitable partner for [2 + 2]-cycloaddition with allenes. Diphenylke-tene and dimethylketene react readily with tetramethylallene at room temperature to give 2-isopropylidenecyclobutanones in good yields [49]. 

A benzene ring can act as the diene in the intramolecular [4 + 2]-cycloaddition with an activated allene. Thus, aryl allene carboxylates 147 gave tricyclic lactones 148 (Table 12.10) [124],... 

Although allene itself is reluctant to react with ordinary 1,3-dienes, it underwent successful [4+2]-cycloadditions with relatively reactive cyclopentadienes to afford 5-methylenebicyclo[2.2.1]hept-2-ene derivatives [145]. 

Like alkenes, methoxyallene undergo [5 + 2]-cycloaddition with the oxidopyrylium ion formed from the precursor 254 and triethylamine. The allenic terminal C=C bond adds from its sterically less encumbered face to afford the [5 + 2]-cycloadduct [186],... 

The reaction is versatile and proceeds with a variety of cyclic and acylic alkenes substituted with alkyl, aryl, vinyl and heteroatom substituents. Allene derivatives also undergo cycloaddition with nitrones ". A variety of cyclic and acyclic aliphatic nitrones bearing aliphatic and aromatic substituents has been tested. The reaction is, however, relatively sensitive to steric constraints and proceeds easily only for mono- and disubstituted alkenes. Steric requirements for a nitrone molecule are similar and, although several reactions with R, R2 are known, good yield has been achieved only with R = H (equation 105). 

Finally, in a very recent disclosure, Lee et al. (165) approached the total synthesis of arteminolide using a [5 + 2] cycloaddition strategy with an oxidopyrylium ion. Despite its long history of use, Lee was the first to utilize an allene moiety both in an intra- and an intermolecular cycloaddition with oxidopyrylium ions. By utilizing a pyrone cycloaddition precursor (294) similar to those used in the Wender phorbol synthesis, Lee was able to synthesize various ring sizes and... 

The practical value of this type of reaction is restricted to symmetrical allenes with vastly different reactivities. Since the less reactive allene has to be present in excess or otherwise homodimerization competes, this allene has to be readily available in large quantities. An example of such a mixed dimerization is the cycloaddition of allene (2) with cyclonona-l,2-di-ene (1). ... 

Allene ketene cycloadditions are of greater synthetic utility than cither mixed allene dimerization or mixed ketene dimerization. In this class of reaction the ketene is the more reactive species and homodimerization of ketene can be minimized by use of excess allene. Such cycloadditions always result in 2-alkylidenecyclobutanones with the sp carbons of both moieties forming the initial bond. In substituted allenes and ketenes, mixtures of stereoisomers of 2-alkylidenecyclobutanones are obtained with very little stereoselectivity, the stereoisomers arise from cisUrcins isomerism in the cyclobutane ring and EjZ isomerism of the exocyclic double bond. In unsymmetrically substituted allenes some regiochemical preference for ketene cycloaddition is observed. Examples of dimethylketene allene cycloadditions are summarized in Table 1,2... 

Diphenylketene and more reactive haloketenes will undergo cycloaddition with allenes such as 1,1-dimethylallene giving regioisomeric mixtures of cyclobutanones. Yields of these reactions are only modest5-7 and distributions of isomers are solvent dependent, which is indicative of a nonconcerted process involving ionic intermediates.8... 

Another reactive ketene which undergoes efficient cycloaddition with allenes is tert-butyl-cyanoketene (TBCK). Again mixtures of isomeric cycloadducts are obtained when unsymmet-rically substituted or 1,3-disubstituted allenes are employed.10-12... 

A [2 + 2] cycloadduct 29 is also obtained with ethoxyallene (28) and 2-methylacrylaldehyde reflecting the opposite regiochemistry for allene cycloaddition.22... 

Some of the earlier studies using partially resolved allenes (1,3-dimethylallene and l,3-di-/ert-butylailene) in cycloadditions with dimethylketene and terf-butylcyanoketene reported some asymmetric induction in the resulting 2-alkylidenecyclobutanones,2 3 however, no optical purity measurements were reported. Furthermore, these reactions arc of limited value due to partial racemization accompanying the intermediacy of zwitterionic intermediates (see Section 1.3.3.). 

The intramolecular 2 + 2-photo-cycloadditions of optically active allenesilanes (5) with enones and enoates produce silyl-substituted exo-methylenecyclobutanes (6) in high enantiometric excess. Photo-desilation leads to the parent unsaturated exo-methylenecyclobutanes (7) (Scheme 3).19 The cycloaddition of naphthoquinone to allyltrimethylsilane in the presence of Me2 A1C1 yields the expected 2 + 2-cycloadduct that slowly rearranges to the 2 + 3-adduct.20 hi the presence of bases, Cephalosporin triflates (8) undergo 2 + 2- and 4 + 2-cycloaddition with alkenes, alkynes, and dienes via an intermediate six-membered cyclic allene (9) (Scheme 4).21... 

Moricini and Kelly [75] have reported the synthesis of spiro-fi-lactams 6 containing an exocyclic double bond (Scheme 2) by the 1,2-dipolar cycloaddition of symmetrically/unsymmetrically substituted allene 4 with chlorosulfonyl isocyanate 5 in ether. 

As mentioned in the introduction [lc], no selectivity was observed in early dimerization experiments of 1. But when other partners were offered, the corresponding crossdimerizations were quite selective. Probably methylene metallacyclopentenes 2 [4], which could be isolated, are intermediates that then react with the other partners. Generally, the related 1,3-dienes are less reactive than 1 with its reactive allenic double-bond and do not react in a similar manner [4a]. Rh-catalyzed [4+1] cycloadditions with CO as a second reaction partner led to alkylidene cyclopentenones 3 and 4 [4, 5], while in Pd-catalyzed reactions where 1 was generated in situ and a base was present, only 4 [6] was formed. When Pt(0) was used instead of Rh(I) in the carbonylation reaction, both in the presence of the (R,R)-DuPHOS-ligand, opposite enantiomers of 3 were obtained [5b], This observation still needs a precise explanation. [Fe(CO)5]-mediated reactions of diallenes form dialkylidene cyclopentenones 7 (Scheme 2, here 10 mol-% of catalyst are needed) [7],... 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

Allenic selenoketenes 129, generated by [3,3] sigmatropic rearrangements, react with primary amines to afford 2-imino-277-5,6-dihydroselenines 130 (Scheme 12) <2001JOC4099>. This reaction appears to be the first example of a selenoketene-allene cycloaddition. Uncyclized allenic selenoamides 131 are by-products in the reactions and are the only products when the reaction is carried out with secondary amines. 

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