Dipoles of the Allyl Type

Upon heating a toluene solution of morpholinoallenes 79 at 120-130°C, in a Schlenk tube, benzazepines 81 are formed in quantitative yield. The first step in this transformation is postulated as the [l,4]-shift of an NCH2 

In the preceding work (97T14687) there is also a brief mention of the transformation of the diphenyl epiminohexadiene 99 into the dihydro- 

As an extension of their work on the carbonyl ylides, Eberbach and co-workers have published a series of papers on the intramolecular reac- 

The most important competition in this sequence is between the 6it cy-clization process, affording the 2-acylpyrroles 123, and the Wolff rearrangement—producing pyridones 124 via ketenes 120. The product distribution 

The same reaction course was observed using different cyclic analogs of 113. The -substituted pyridine N-oxides 125, a special class of nitrones, 

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Trifluoromethyl-substituted 1,3-dipoles of the allyl type. Trifluoromethyl-substituted azomethine imines ate readily available on reaction of hexafluo-... 

Dipoles of the allyl type are bent, whereas the propargyl/allenyl types, which bear an additional rr-orbital orthogonal to the allyl type of molecular orbital, have a linear structure. 

The presence of two O—O bonds renders primary ozonides so unstable that they decompose immediately (Figures 15.47 and 15.48). The decomposition of the permethylated symmetric primary ozonide shown in Figure 15.47 yields acetone and a carbonyl oxide in a one-step reaction. The carbonyl oxide represents a 1,3-dipole of the allyl anion type (Table 15.2). When acetone is viewed as a dipolarophile, then the decomposition of the primary ozonide into acetone and a carbonyl oxide is recognized as the reversion of a 1,3-cycloaddition. Such a reaction is referred to as a 1,3-dipolar cycloreversion. 

Dipoles of the allyl atiioti type (i) Azomethine oxides (nitrones)... 

A 1,3-dipole as shown in Schemes 6-5 and 6-6 corresponds to a system with three parallel atomic p-orbitals, i.e., to an allyl anion, but without net charge. It is, therefore, called an allyl-type 1,3-dipole. The system may contain, however, an additional 7i-bond in the plane perpendicular to the allyl anion type molecular oribtal, and then belongs to the propargyl - allenyl type. Normally, 1,3-dipoles of this type are linear, whereas those of the allyl type are bent. The term 1,3 relates to the reactivity in these positions, not to formal charges. A series of theoretical studies (e. g., by Hiberty and Leforestier, 1978 Yamaguchi et al., 1980 see review of Houk and Yamaguchi, 1984) clearly show, however, that some of these 1,3-dipoles have considerable biradical character (e.g., O3 53% and CH2N2 28% in ab initio calculations at the 4-3IG level). We will return to biradicals in the mechanistic discussion of Sect. 6.3. 

For the reaction of the allyl-type 1,3-dipoles, the reaction scheme can be generally presented as shown in Figure 1. 

The kind of dipoles that feature in the 1,3-DPCAs are isoelectronic with an allyl or propargyl anion system. They have a 7u-electron system consisting of two filled and one empty orbital, and both ends of the dipole have nucleophilic as well as electrophilic properties. 1,3-Dipoles of the allyl anion type are bent as the system has four electrons in three parallel p -orbitals perpendicular to the plane of the dipole. On the other hand, the presence of a double bond orthogonal to the delocalized 7r-system in the propargyl/aUenyl anion type causes linearity to the dipole (Figure 5.9). 

All 1,3-dipoles contain an allyl anion type n system, i.e., four electrons delocalized over three parallel atomic n orbitals, but, in addition, 1,3-dipoles of the propargyl-allenyl type contain an additional n bond in the plane perpendicular to the allyl anion MO (Fig. 1). 

Azomethine ylides, like azomethinimines, lack a double bond in the sextet structure but have internal octet stabilization and belong to the allyl type of dipoles (121a and 121b). In terms of the PMO theory, azo-... 

Huisgen classifled the 1,3 dipoles into two categories, the allyl type and the propargyl-allenyl type, and suggested that both types of 1,3 dipole should follow the concerted mechanism and that both types of 1,3 dipole and dipolarophiles should approach each other in two parallel planes, forming an envelope-like transition structure. 

Dipolar compounds (1,3-dipoles), first designated by Huisgen [1], are a class of 4tt-electron species that can be represented by zwitterionic (or ylide) forms with a separation of charge over three atoms. Basically, 1,3-dipoles are categorized into two subclasses, including the allyl type (carbonyl ylides, carbonyl imines, azomethine ylides, azomethine imines, and nitrones) and the propargyl/allenyl type (azides, diazoalkanes, nitrile ylides, nitrile imines, and nitrile oxides), as shown in Scheme 16.1. 

The 1,3-dipoles consist of elements from main groups IV, V, and VI. The parent 1,3-dipoles consist of elements from the second row and the central atom of the dipole is limited to N or O [10]. Thus, a limited number of structures can be formed by permutations of N, C, and O. If higher row elements are excluded twelve allyl anion type and six propargyl/allenyl anion type 1,3-dipoles can be obtained. However, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions have only been explored for the five types of dipole shown in Scheme 6.2. 

In the 1,3-dipolar cycloaddition reactions of especially allyl anion type 1,3-dipoles with alkenes the formation of diastereomers has to be considered. In reactions of nitrones with a terminal alkene the nitrone can approach the alkene in an endo or an exo fashion giving rise to two different diastereomers. The nomenclature endo and exo is well known from the Diels-Alder reaction [3]. The endo isomer arises from the reaction in which the nitrogen atom of the dipole points in the same direction as the substituent of the alkene as outlined in Scheme 6.7. However, compared with the Diels-Alder reaction in which the endo transition state is stabilized by secondary 7t-orbital interactions, the actual interaction of the N-nitrone p -orbital with a vicinal p -orbital on the alkene, and thus the stabilization, is small [25]. The endojexo selectivity in the 1,3-dipolar cycloaddition reaction is therefore primarily controlled by the structure of the substrates or by a catalyst. 

In Chapter 10 of Part A, the mechanistic classification of 1,3-dipolar cycloadditions as concerted cycloadditions was developed. Dipolar cycloaddition reactions are useful both for syntheses of heterocyclic compounds and for carbon-carbon bond formation. Table 6.2 lists some of the types of molecules that are capable of dipolar cycloaddition. These molecules, which are called 1,3-dipoles, have it electron systems that are isoelectronic with allyl or propargyl anions, consisting of two filled and one empty orbital. Each molecule has at least one charge-separated resonance structure with opposite charges in a 1,3-relationship, and it is this structural feature that leads to the name 1,3-dipolar cycloadditions for this class of reactions.136... 

The dipolar structure 1 describes the chemical behavior of thiocarbonyl ylides best, although other mesomeric forms have been used for the representation of the electronic structure of these dipoles. The parent compound, thioformaldehyde (5)-methylide (1), was studied by means of spectroscopic and theoretical methods (2-5), which showed that the molecule possesses a bent allyl-type structure (6). According to theoretical calculations, structures lA and IB have the largest contribution (31.5% each) in the representation of the electronic structure, whereas 1C, which reflects the 1,3-dipolar character, has only a 4.2% contribution (5). 

Several nickel derivatives of the type [ANiXfi (A = allyl, X = halogen) are known, but they are very much less stable to air than the palladium compounds (76, 77). The small dipole-moment of bis (ally lnickel bromide) may mean that the nickel-bromine bridges are not coplanar (76). 

Mechanistically, this sequence can be rationalized by initial alkynone formation upon coupling of acid chloride 7 and aUcyne 4 furnishing the alkynone 8, which now can act as a dipolarophile (Scheme 18). The amount of triethylamine is sufficient to deprotonate the l-(2-oxoethyl)pyridinium bromide 25 giving rise to the zwitter-ionic pyridinium ylide 27, an allyl-type dipole suitable for the subsequent 1,3-dipolar cycloaddition to give the dihydroindolizine 28. Under either aerobic or anaerobic conditions in the final cycloaddition step oxidative aromatization directly furnishes the desired indolizines 26. 

In the case of cycloadditions with allyl-type" dipoles1, either one e.g., with nitrones, azomethine imines or two e.g., with azomethine ylides, additional stereocenters can be created depending on the structure of the dipole ... 

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