Mechanism of Cycloaddition Reactions

The Basic Mechanisms of Cycloaddition Reactions of Carbonyl Compounds with Conjugated Dienes... 

The mechanism of cycloaddition reaction of maleic anhydride with anthracene promoted by US irradiation has been the subject of many controversies [32, 37]. Recent work of Da Cunha and Garrigues [35] shows that the reaction proceeds in toluene solution in the 60 85 °C temperature range in 6 3 h. 

Jug and co-workers investigated the mechanism of cycloaddition reactions of indolizines to give substituted cycl[3,2,2]azines <1998JPO201>. Intermediates in this reaction are not isolated, giving evidence for a concerted [8+2] cycloaddition, which was consistent with results of previous theoretical calculations <1984CHEC(4)443>. Calculations were performed for a number of substituted ethenes <1998JPO201>. For methyl acrylate, acrylonitrile, and ethene, the concerted [8+2] mechanism seems favored. However, from both ab initio and semi-empirical calculations of transition states they concluded that reaction with nitroethene proceeded via a two-step intermolecular electrophilic addition/cyclization route, and dimethylaminoethene via an unprecedented two-step nucleophilic addition/cyclization mechanism (Equation 1). 

Density functional theory and MC-SCF calculations have been applied to competing concerted and stepwise mechanisms of cycloaddition reactions. ... 

The proposed mechanism of cycloaddition reaction of C02 with epoxides catalyzed by BrTBDPEG150TBDBr is depicted in Scheme 5.6. 

The mechanism of the reaction of ethyl glyoxylate 4 with 2,3-dimethyl-l,3-hutadiene 5 leading to the ene product 7 is shown in Scheme 4.5. This brief introduction to the reaction mechanism for cycloaddition reactions of carhonyl compounds activated hy Lewis acids indicates that many factors influence the course of the reaction. 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

The reaction of methyl acrylate and acrylonitrile with pentacarbonyl[(iV,iV -di-methylamino)methylene] chromium generates trisubstituted cyclopentanes through a formal [2S+2S+1C] cycloaddition reaction, where two molecules of the olefin and one molecule of the carbene complex have been incorporated into the structure of the cyclopentane [17b] (Scheme 73). The mechanism of this reaction implies a double insertion of two molecules of the olefin into the carbene complex followed by a reductive elimination. 

Thermally induced intra-intermolecular criss-cross cycloaddition of nonsymmetrical azines 363 in the presence of phenyl isocyanate provides the corresponding products of the mixed criss-cross cycloaddition 364 (Scheme 55) <2002TL6431>. Two different reaction mechanisms, intra-intermolecular and inter-intramolecular, of the mixed criss-cross cycloaddition with opposite sequence of reaction steps are possible. Quantum chemistry calculations suggest the intra-intermolecular mechanism as the most probable mechanism of this reaction <2004CCC231>. 

Imino-1,2,4-thiadiazoles such as 27 react with electron-deficient alkynes to afford arylimino thiazoles such as 28. There has been some speculation as to the mechanism of this reaction, which may involve a 1,3-dipolar cycloaddition or a stepwise nucleophilic addition (Equation 6) <1996CHEC-II(4)307>. 

Formation of nitrones can be achieved in the first stage of a Krohnke type reaction in which p-n trosodi methy 1 an dine reacts with 2-oo-bromoacetylphenoxathiin in alkaline medium (336). The synthesis of a series of cyclic nitrones of structure (182) has been achieved by regioselective, and by an unusual [3 + 2] cycloaddition of a-nitrosostyrenes (181) to 1,3-diazabuta-l,3-dienes (180) (Scheme 2.64) (337a). Theoretical studies of the substitution effect at the imine nitrogen on the competitive [3 + 2] and [4 + 2] mechanisms of cycloaddition of simple acyclic imines with nitrosoalkenes have been reported (337b). 

The mechanism of this reaction has not been studied in detail. However, it can be represented as a sequence of reactions. The first reaction is, in fact, [3+ 2]-cycloaddition of olefin to furoxan (161). Under severe conditions, the resulting intermediate A undergoes fragmentation to give five-membered cyclic nitronate B. The latter is involved in the usual addition reaction with an excess of olefin to form isolable bicyclic product (162) (301, 378, 379). 

Azolotriazines can be formed by cycloaddition reactions between diazoazoles and various substituted alkynes. In order to determine the mechanism of these reactions, semi-empirical AMI, MNDO, and PM3 calculations were run <1999JMT103>. Depending on the nature of the alkyne partner, these condensations may be viewed either as [7+2] cycloadditions, directly forming azolotriazines, or as [3+2] cycloadditions forming spirobicyclic intermediates, which quickly rearrange to azolotriazines. 

The mechanism of the reaction is assumed to involve a cycloaddition to a four-mem-bered ring followed by cycloreversion giving the product. 

Hong and co-workers have described a formal [3-t-3] cycloaddition of a,P-unsaturated aldehydes using L-proline as the catalyst (Scheme 72) [225], Although the precise mechanism of this reaction is unclear a plausible explanation involves both iminium ion and enamine activation of the substrates and was exploited in the asymmetric synthesis of (-)-isopulegol hydrate 180 and (-)-cubebaol 181. This strategy has also been extended to the trimerisation of acrolein in the synthesis of montiporyne F [226],... 

Cycloaddition reactions of sulfonyl isothiocyanate 76 and, -disubsti-tuted enamines were studied by Schaumann et The mechanism of cycloaddition is postulated to consist of two steps, originating with the formation of the zwitterionic adduct 77. 

The reaction of 77 with alkynes has further been elaborated for the synthesis of substituted phthalonitriles 81. An alternative for the synthesis of these compounds is the cycloaddition reaction of 77 with enamines followed by a retro-Diels-Alder loss of N2 and elimination of the amine (Scheme 16). Generally, more forcing reaction conditions are required and lower yields are obtained in reactions with alkynes than in reactions with enamines, for example, 4-ethyl-5-methylphthalonitrile is obtained in 51% yield from 2-pentyne (xylene, 150°C, 18 days) and in 73% yield from 4-(l-ethylprop-l-en-l-yl)morpholine (CHCI3, 70°C, 7 days) <1998T1809>. The mechanism of the reaction with enamines has been studied in detail. This revealed a [1,5] sigmatropic rearrangement in the cyclohexa-2,4-dien-1-amine intermediates formed after the loss of N2 <1998T10851>. 

The generation of a nitrile oxide bearing a carbamoyl group (i.e., 16) was effected by treating 4-nitro-3-isoxazoline-5-one (15) with a mixture of acetonitrile and water (Scheme 6.5). Although the mechanism of this reaction is not clear, the method allows for the formation of a functionalized nitrile oxide (16) and subsequent cycloaddition under mild conditions (91). 

Diazo(trimethylsilyl)methyl lithium reacts with white phosphorus (P4) in THF to form the 5-trimethylsilyl-l,2,3,4-diazadiphospholide lithium salt (282). This novel heteroaromatic system formally represents the cycloaddition product of a diazo dipole and a P=P bond. However, the tme mechanism of this reaction is not known. 

A third type of cycloaddition reaction has recently been reported.74 When 5,5,6-trimethyl-3,6-heptadien-2-one 58 was irradiated, two intramolecular cycloaddition products 59 and 60 were obtained, affording the first example of dihydropyran formation from this reaction. Although a reasonable mechanism, analogous to that leading to oxetane formation, has been proposed, it was recognized that 58 is a special type... 

The reactions of silylenes with 1,3-dienes giving the corresponding 3-silolenes are typical of the cycloaddition reactions of silylenes. The mechanism of these reactions has been investigated in detail, " " and it has been proposed that the reactions of silylenes with 1,3-dienes proceed via initial [1 + 2] addition followed by the isomerization of the resulting 2-vinylsiliranes to the corresponding 3-silolenes. However, the observation and isolation of the intermediary 2-vinylsiliranes has been limited to only a few examples because vinylsiliranes readily isomerize... 

If the motion had been disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse reaction is also conrotatory. In contrast, the photochemical cyclobutene—1,3-diene interconversion is disrotatory in either direction.368 On the other hand, the cyclohexadiene—1,3,5-triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling results are a consequence of the symmetry rules mentioned in Chapter 15 (p. 846).Vl,As in the case of cycloaddition reactions, we will use the frontier-orbital and Mdbius-HQckel approaches.37"... 

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