Cycloaddition reactions dipolar mechanism

A model for the mechanism of the highly enantioselective AlMe-BINOL-cata-lyzed 1,3-dipolar cycloaddition reaction was proposed as illustrated in Scheme 6.13. In the first step nitrone la coordinates to the catalyst 11b to form intermediate 12. In intermediate 13, which is proposed to account for the absolute stereoselectivity of this reaction, it is apparent that one of the faces of the nitrone, the si face, is shielded by the ligand whereas the re face remains available... 

The stereochemical characterization of the adduct 53 follows from its NMR spectrum and a comparison with that of the l-(2-thienyl) compound (54). The aSY-exo configuration for the adducts 51 and 52 is consistent with the NMR spectra (hydrogen atoms at C-2, C-3, C-5, and C-6 all equivalent), with the proposed mechanism of formation, and with the failure of the related tetramethyl ester to xmdergo N-acetylation even in very vigorous conditions. N-substituted derivatives of compounds such as 51-53 may be obtainable directly from similar dipolar cycloaddition reactions of mesoionic N-substituted oxazolium 5-oxides, although the formation of only the N-methyl derivative of (52) has so far been reported. ... 

The complete stereoselectivity of the reaction, however, is difficult to reconcile with a two-step process. This earlier controversy, however, has long since been resolved. For example, when considering results of the cycloaddition of p-nitrobenzonitrile oxide with cis- and trani-l,2-dideuterioethylene (111), the experiments clearly established that, within experimental limits of detection, the reaction is > 98% stereoselective. If diradical intermediates were operative, significant scrambling of configuration should be observed in the products. These and other results confirm a concerted mechanism for the 1,3-dipolar cycloaddition reaction (15). 

It is known that aryl azides undergo 1,3-dipolar cycloaddition reaction with bis(trifluoromethyl)thioketene 156 to form the yellow A3-l,2,3,4-thiatriazolines 159 in very low to fair yield supporting the mechanism of reaction of this thioketene with hydrazoic acid (Equation 14) <1978JOC2500>. 

An entirely different description emerges for the two 1,3-dipolar cycloaddition reactions that we have studied [3,4]. For such systems, the bond breaking and bond formation involves instead the shifts of well-identifiable orbital pairs, rather than any spin recouplings. Such heterolytic mechanisms, that do not pass through an aromatic structure, now seem to be a likely outcome of studies on other gas-phase concerted 1,3-dipolar cycloaddition reactions. 

Theoretical studies are also done to interpret the synthesis reactions and mechanism of reactions. The regioselectivity of 1,3-dipolar cycloaddition reaction between substituted trimethylstannyl-ethynes and nitrile oxides yielding isoxazoles, was interpreted by the application of frontier electron theory <93CPB478>. By the combination of experimental and molecular orbital (ab initio) studies, a multistep mechanism is proposed for unimolecular radical chemistry of isoxazoles in the gas phase <920MS(27)317>. 

The Grigg group also studied the tautomerization of oximes to N-H nitrones followed by a dipolar cycloaddition reaction. The well-known H-bonding dimeric association of oximes, in both solution and the solid state, allows for a concerted proton transfer to occur and provides nitrone 56 (Scheme 11) (91TL4007). Another possible pathway involves tautomerization of the oxime to an ene-hydroxylamine (i.e. 57) followed by a 1,4-hydride shift to give nitrone 58. To probe the ene-hydro-xylamine mechanism, deuterated oxime 59 was prepared and heated at 140 °C in xylene. The physical characteristics of the isolated product, however, were consistent with compound 60, suggesting that the 1,2-prototropic reactions does not proceed... 

The most extensively studied 1,3-dipolar cycloaddition reaction so far is the prototype reaction of acetylene with fulminic acid (Scheme 1-4). The early GVB calculations by Harcourt and Little attempted to resolve the controversy between Firestone s stepwise biradical mechanism and the concerted mechanism for the 1,3-dipolar reaction [95]. Which mechanism... 

Oxidation of Alkenes to Oxirans by Peroxy-acids. The mechanism of the reaction of m-chloroperbenzoic acid with double bonds has been investigated through a study of the epoxidation of a series of cycloalkenes (of ring sizes 5,6,7,8, and 12) and substituted cyclohexenes.The second-order rate constants were determined in CHCI3 at 0—30°C, and the data support a 1,3-dipolar cycloaddition reaction. 

The 1,3-dipolar cycloaddition reactions of munchnones with olefinic dipolarophiles continues to be of enormous interest in regard to both mechanisms and synthetic applications. Unlike the comparable cycloadditions with acetylenic dipolarophiles that yield only pyrroles, reactions of munchnones with olefinic dipolarophiles can lead to a variety of interesting products. 

In the mechanism of the CuAAC reaction described above, the metal catalyst activates terminal alkyne for reaction with a Cu-coordinated azide. This mode of reactivity operates with other dipolar reagents as well. In fact, the first example of a copper-catalzyed 1,3-dipolar cycloaddition reaction of alkynes was reported for nitriones by Kinugasa in 1972 [124]. An asymmetric version of the Kinugasa reaction was developed by Fu et al. in 2002 [125, 126]. 

REVIEW This volume is highly recommended to all those who want to stay abreast of developments In the mechanisms and synthetic applications of 1,3-dipolar cycloaddition reactions. The writers have realized a good balance between the summary of achievements and the reporting of gaps in understanding or remaining synthetic challenges. The articles are well written, they are amply illustrated with equations or schemes. ... 

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