Intermolecular cycloadditions dimerization reactions

In solution, phenylcarbene behaves normally it undergoes routine intermolecular cycloadditions and insertions, for example. In the gas phase, in which intermolecular reactions are difficult or impossible, phenylcarbene produces a set of dimers... 

The concept of the conservation of orbital symmetry can be extended to intermolecular cycloaddition reactions which occur in a concerted manner. The simplest case is the dimerization of ethylene molecules to give cyclobutane, the 2n + 2je cycloaddition. The proper geometry for the concerted action would be for the two ethylene molecules to orient one over the other. Two planes of symmetry are thereby set up -perpendicular to the molecular plane bisecting the bond axes oy-parallel to the molecular plane lying in between the two molecules (Figure 8.10). 

For thermally induced [2 + 2] cycloadditions, the concerted mechanism is operative only in particular cases, such as in the reactions between an alkene or alkyne and a ketene. The ketene can be generated directly in the reaction mixture from the appropriate acid chloride with triethylamine. The cycloaddition reaction is stereospecific and occurs exclusively in a cis fashion. Although the intermolecular cycloaddition with ketene itself proceeds in poor yields due to the propensity of the unsubstituted ketene to undergo dimerization, it is quite an efficient reaction with ketenes containing electron-withdrawing substituents. Usually, a-chloro ketenes are employed as reagents formed in situ from the corresponding a-chloro acid chlorides. Typical examples are represented in the preparation of cycloadducts such as 378 and 379 (Scheme 2.127). The latter cycloadduct, prepared in modest yield (ca. 20%),... 

For the structure determination of flavoskyrin (556), a yellow metabolite of Penicillium islandicum, a biosynthetic pathway involving Diels-Alder cycloaddition (Scheme 70) has been proposed by Shibata and co-workers (73T3721). The dimerization of l-oxo-l,2,3,4-tetrahydroanthraquinone derivative 551 has been elucidated by intermolecular Diels-Alder reaction with exo approach of the monomers in the model experiment as formulated in 553. Eventually, an enolized form of tetrahydroemodin (552) was considered as a monomeric precursor which could be dimerized by the intermolecular Diels-Alder reaction to form flavoskyrin (556). 

Another example of chemical reaction which gives different products in ball mill than solution chemistry is phthalazine addition to fullerene [11], In the ball-milling conditions, intermolecular [4+2] cycloaddition of phthalazine 16 takes place, followed by spontaneous nitrogen elimination from 1 1 adduct 17. This adduct further in sohd state undergoes intermolecular cycloaddition and formation of the corresponding dimer 20 (Scheme 7.5). On the other hand, when reaction is carried out in solution, an intramolecular [4+4] addition takes place with formation of product 20, followed by retro- [2+2+2] addition and formation of product 21. This reaction sequence is characteristic for fullerene chemistry, which is not observed in analogous cycloaddition reactions of phthalazines with norbomenes [12]. 

Intermolecular cycloaddition reactions catalyzed by Cu(I) were studied by Salomon and Kochi, by Mackor and by others. The use of better soluble CuOTf instead of Cu-halides allowed reactions to be run more effectively and cleaner. Reactions studied are the 2 -t- 2 cycloaddition of norbomene giving the exo-trans-exo isomer exclusively (97 %), the analogous reaction with e d(9-dicyclopentadiene as substrate, the codimerization of norbomene with cyclooctene, the dimerization of cyclopentene, cyclohexene, cyclo-heptene and mixtures thereof. 

DFT studies of the intramolecular ene-like (or the so-called 1,3-dipolar ene) reaction between nitrile oxides and alkenes show that this reaction is a three-step process involving a stepwise carbenoid addition of nitrile oxide to form a bicyclic nitroso compound, followed by a retro-ene reaction of the nitrosocyclopropane intermediate. The competitive reactions, either the intramolecular [3 + 2] cycloaddition between nitrile oxides and alkenes or the intermolecular dimerization of nitrile oxides to form furoxans, can overwhelm the intramolecular 1,3-dipolar ene reaction if the tether joining the nitrile oxide and alkene is elongated, or if substituents such as trimethylsilyl are absent (425). 

In our initial studies on the [5+2] cycloaddition, several metal catalysts were screened. Rhodium(I) systems were found to provide the optimum yields and generality [26]. Since the introduction of this new reaction in 1995, our group and others have reported other catalyst systems that can effect the cycloaddition of tethered VCPs and systems. These new catalysts thus far include chlororhodium dicarbonyl dimer ( [RhCl(CO)2]2 ) [27], bidentate phosphine chlororhodium dimers such as [RhCl(dppb)]2 [28] and [RhCl(dppe)]2 [29], and arene-rhodium complexes [(arene)Rh(cod)] SbFs [30]. [Cp Ru(NCCH3)3] PFg has also been demonstrated to be effective in the case of tethered alkyne-VCPs [31], but has not yet been extended to intermolecular systems or other 2n -components. 

The dimerization of thioformylketene was investigated by B3LYP and G3MP2B3 methods. The 4 + 4-pathway has the lowest energy barrier and calculations suggest that the reaction is pseudopericyclic.231 The stereospecific intramolecular 4 + 4-cycloaddition reaction between cyclohexadiene iron tricarbonyl complex and appended dienes (198) generates cyclooctadiene tricyclic adducts (199) (Scheme 56).232 The first example of an asymmetric intermolecular 4 + 4-photocycloaddition reaction in solution between 9-cyanoanthracene and chiral 2-methoxy-l-naphthamides has been reported. The frozen chirality is effectively transferred to the optically active product.233... 

Interestingly, when using copper(I)triflate, the cyclopentadiene dimer 14 reacts in an intermolecular way, leading to the cydobutane 15 (reaction 5) [22], When the same substrate is transformed in the presence of the triplet sensitizer acetone, an intramolecular [2 + 2] cycloaddition takes place and the cage hydrocarbon compound 16 is formed. Obviously, the formation of a copper complex intermediate involving both alkene double bonds of the substrate is unfavorable in this case. 

The structural similarities between S-alkylthiophenium salts and thiophene sulfoxides have prompted the suggestion that both classes are antiaromatic (70JA7610, 70JCS(C)1764). Thiophene sulfoxides are exceptionally reactive, undergoing spontaneous Diels-Alder dimerization unless stabilized by bulky substituents at the 2- and 5-positions. This type of reactivity is reminiscent of cyclobutadiene. In stark contrast to the sulfoxides, S-alkylthiophenium salts show no tendency to take part in Diels-Alder reactions either in an intra- or intermolecular sense. Pentamethylthiophenium hexafluorophosphate (11, X = PFg ) was shown to be completely unreactive toward both electron-rich and electron-deficient dienophiles under conditions where thiophene sulfoxides undergo efficient cycloaddition reactions. 

Stilbene and its derivatives have often been used in photochemical [2-1-2] cycloadditions. The intermolecular dimerization presented by H. Meier of 2,3-fcij(2-phenylethenyl)-naphthalene directly leads to cyclophane via two [2-1-2] cycloadditions in one step. The yield is surprisingly very high and comparable with those of intramolecular reactions presented by W. H. Laarhoven. Various examples of vinylstilbenes are photolyzed to form cyclobutanes via a "crossed" addition. Even [2a-H2jt] cycloadditions and rearrangements involving H-transfer are utilized to construct unusual bicyclic or tricyclic compounds. 

Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizono various bis-enolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyano-anthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization ci the silane-bridged 2>. s-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-cyclohexadiene. He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed Bauld and which may be called "hole catalyzed Diels-Alder reaction". 

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