As 1,3-dipoles

Although the most general cycloaddition reaction of diazo compounds is that they react as 1,3-dipoles, recently some reactions have been reported in which they react as 1,2-dipoles,... 

Frontier molecular orbital theory correctly rationalizes the regioselectivity of most 1,3-dipolar cycloadditions (73JA7287). When nitrile ylides are used as 1,3-dipoles, the dipole... 

Some researchers have elaborated synthesis of PCSs employing bis(nitrile oxide)s as 1,3-dipoles and diynes, dinitriles, and a number of other compounds as dipolaro-philes154-156). 

The intermolecular dimerization of nitrile oxides has been described as a procedure to prepare Fx with identical substituent both in the 3 and 4 position (Fig. 3). This procedure is a [3 -F 2] cycloaddition where one molecule of nitrile oxide acts as 1,3-dipole and the other as dipolarophile [24-26]. Yu et al. has studied this procedure in terms of theoretical calculus [27,28]. Rearrangement of isocyanates competes with the bimolecular dimerization, with the former becoming dominant at elevated temperatures. 

Terrier et al. have widely described Bfxs 4-nitro-substituted participating in a series of Diels-Alder processes. Bfx 4-nitro-substituted system could participate as diene, C = C - C = C system, or heterodiene, C = C - NO2 system, in an inverse electron demand reaction [62,63] or as dienophile, C = C or N = O systems, in a normal electron demand reaction [64-68]. Fxs have been reported as 1,3-dipole through the substructure C = - 0 reacting with... 

The 3-oxo-2-pyrazolidinium ylides 315, easily available by reaction of the corresponding pyrazolidin-3-one with aromatic aldehydes, function as 1,3-dipoles in cycloaddition reactions with suitable alkenes and alkynes to provide the corresponding products. When unsymmetrical alkynes are used, mixtures of both possible products 316 and 317 are usually obtained (Equation 45). The regioselectivity of cycloadditions of the reaction with methyl propiolate is influenced by the substituents on the aryl residue using several 2,6-di- and 2,4,6-trisubstituted phenyl derivatives only compound 316 is formed <2001HCA146>. Analogous reactions of 3-thioxo-l,2-pyrazolidinium ylides have also been described <1994H(38)2171>. 

In an attempt toward electron-rich and electron-deficient multiple bonds as well as 1,3-dipoles, the triafulvene system may develop functionalization of a dipolarophilic, dienophilic, and diene component. Rigorous proof for a concerted or a stepwise mechanism, e.g. via dipolar intermediates, for any of the numerous reactions investigated cannot be presented. Therefore the following classification has been chosen from a more or less formal point of view. 

Structure B is of most interest. It is responsible for the activity of nitronates as 1,3-dipoles in [3+ 2]-cycloaddition reactions. This is the most important aspect of the reactivity of nitronates determining the significance of these compounds in organic synthesis (see e.g., Ref. 267). In addition, this structure suggests that nitronates can show both, O -nucleophilic properties, that is, react at the oxygen atom with electrophiles, and a-C-electrophilic properties, that is, add nucleophiles at the a-carbon atom. 

Intramolecular [3+2]-Cycloaddition ofNitronates These reactions are more efficient than analogous intermolecular transformations of nitronates as [1,3]-dipoles, and, consequently, activation of the dipolarophilic fragment is not required. However, another problem arises, that is, the construction of the starting substrate combining the nitronate fragment and the C,C double bond in the required positions. 

If nitrones have been widely used as 1,3-dipoles in the synthesis of hexahydro-isoxazolo[2,3- ]pyridines, the use of nitroacetates such as 92 in the cycloaddition sequence allows for an efficient access to hexahydro-isoxazolo[2,3-tf] pyridin-7-ones such as 93 after spontaneous dehydration (Scheme 30) <2000JOC499>. 

Allenic esters such as 185 can act not only as dipolarophiles but also, at least formally, as 1,3-dipoles, which was shown by Xu and Lu during the phosphane-cata-lyzed reaction with N-tosylimines 387 (Scheme 7.52) [358, 359]. The heterocycles 388 are formed at least in moderate and mostly in excellent yields, if R1 is an aryl or a vinyl group. The formation of the products can be explained by reversible nucleophilic addition of the phosphane to 185 (cf. Section 7.3.1) followed by nucleophilic addition of the resulting intermediate to the imine 387. 

Alkynes have been well explored as dipolarophiles in the [3 -t- 21-cycloaddition with almost all possible 1,3-dipoles (78), whereas the reaction of iminoboranes as dipolarophiles has focused on covalent azides as 1,3-dipoles. Most well-characterized iminoboranes were reacted with phenyl azide, according to Eq. (52) (11-14,17, 20). 

The radical cations (47) produced by T oxidation of aryl aldehyde hydrazones acted as 1,3-dipoles in reaction with nitriles to form, after a second T oxidation, 1,2,4-triazoles (Scheme 4) (85TL5655). 

Organic azides can also act as 1,3-dipoles and undergo [3+2] cycloadditions to the [6,6] double bonds of Cjq, yielding a [6,6] triazoline intermediate 164 (Scheme 4.28), which in some cases can be detected or even isolated [166-170]. 

Anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxides (4) and anhydro-5-thiolo-l,2,3,4-oxatri-azolium hydroxides (5) do not act as 1,3-dipoles <79JCS(P1)732>. However, anhydro-5-phenylamino-1,2,3,4-oxatriazolium hydroxides (16) react with aryl isocyanates with exchange of the exocyclic aryl group <79JCS(P1)736>. This process can be explained in terms of a 1,3-dipolar cycloaddition to give (18) which then eliminates phenyl isocyanate producing (19) (Scheme 3). 

Another nonclassical heterocycle, thienol3,4-cJpyrazole, was synthesized, utilizing the ability of mesoionic ring systems to act as 1,3 dipoles in cycloadditions. Condensation of IV-phenylsydnone (162) with dibenzoylacetylene formed 3,4-dibenzoyl-1-phenylpyrazole (163) (85%) with phosphorus pentasulfide in refluxing pyridine, this gave 85% of 2,4,6-triphenyIthieno[3,4-c]pyrazole (164) [Eq. (44)]. The synthesis of 5-methyl-l,3,4,6-tetraphenylthieno[3,4-c]pyrrole is also described. ... 

Two recent publications feature metal vinylidenes functioning as 1,3-dipole equivalents, as in the Cu-catalyzed Huisgen cyclization (Section 9.4.5). Fiirstner and coworkers described intramolecular Diels-Alder reactions of unactivated die-nynes catalyzed via a proposed [4+3]-diene/copper vinylidene cycloaddition [59]. 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and 1,3-dipolarophile approach, can be expected to influence the energy of the transition state—and therefore the reaction rate and the structure of the product. This is the essence of frontier molecular orbital (EMO) theory, several accounts of which have been published. 16.317 application of the FMO method to the pericyclic reactions of mesomeric betaines has met with considerable success. The following section describes how the reactivity, electroselectivity, and regioselectivity of these molecules have been rationalized. 

Compounds 98 behave as 1,3-dipoles in cycloaddition reactions with DMAD, ethyl cyanoformate, and alkenes the structure of the adduct 186 from ethyl cyanoformate suggests that reaction is via form 98b.131... 

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