Dipolarophiles nitronate structures

A diastereoselective dipolar cycloaddition of chiral nitrone 80 with alkene dipolarophiles afforded imidazo[ 1,2-3]-isoaxazole (Scheme 9). The conversion via N-O reduction of this ring system with Raney-Ni in methanol gave the corresponding pyrrolo[l,2-A imidazole in 66% yield. The structure has been confirmed by X-ray diffraction crystal stmcture analysis <2000SL967>. 

The enantioselective catalytic 1,3-dipolar cycloaddition of linear or cyclic nitrones to enals was accomplished using the half-sandwich rhodium(III) complex S, Rc)-[(ri -C5Me5)Rh (/ )-Prophos (H20)](SbF6)2 as catalyst precursor [33, 34]. At —25°C, quantitative conversions to the cycloadducts, with up to 95% ee, were achieved (Scheme 10). The intermediate with the dipolarophile coordinated to the rhodium has been isolated and completely characterized, including the X-ray determination of its molecular structure [33, 34]. 

The primary cycloadduct from combination of a dipolarophile with a silyl nitronate is an isoxazolidine. The and NMR spectra are highly informative for the structural determination of these products. Tables 2.7 and 2.8 (21,25,34,35). Both the and NMR data show that HC(5) are shifted downfield relative to HC(3). An expected downheld shift is also observed with electron-withdrawing or conjugating groups. In the absence of functionalization at C(3), there is a significant upfield shift of the corresponding resonance. The IR data is less reliable. The O—N—O stretch is reported to be 1055 cm (Fig. 2.8), however, this stretching... 

Because of the intrinsic structural asymmetry of this dipole, there exist two possible regioisomers resulting from the cycloaddition with unsymmetrical dipo-larophiles. The reaction of a monosubstituted dipolarophile with a nitronate, in a head-to-head fashion provides a 5-substituted isoxazolidine (Scheme 2.4). Alternately, the head-to-tail combination of the coupling partners results in a 4-substituted isoxazolidine. With only a few exceptions (92), the 5-substituted isoxazolidine is formed exclusively. 

Fig. 2.3 shows the core structures of the most important 1,3-dipoles, and what they are all called. As with dienes, they can have electron-donating or withdrawing substituents attached at any of the atoms with a hydrogen atom in the core structure, and these modify the reactivity and selectivity that the dipoles show for different dipolarophiles. Some of the dipoles are stable compounds like ozone and diazomethane, or, suitably substituted, like azides, nitrones, and nitrile oxides. Others, like the ylids, imines, and carbonyl oxides, are reactive intermediates that have to be made in situ. Fig. 2.4 shows some examples of some common 1,3-dipolar cycloadditions, and Fig. 2.5 illustrates two of the many ways in which unstable dipoles can be prepared. 

One important nitrone is a cyclic compound that has the structure below and adds to dipolarophiles (essentially any alkene ) to give two five-membered rings fused together. The stereochemistry comes from the best approach with the least steric hindrance, as shown. There is no endo rule in these cycloadditions as there is no conjugating group to interact across space at the back of the dipole or dipolarophile. The product shown here is the more stable exo product. 

Examples of 1,3-dipoles include diazoalkanes, nitrones, carbonyl ylides and fulminic acid. Organic chemists typically describe 1,3-dipolar cycloaddition reactions [15] in terms of four out-of-plane 71 electrons from the dipole and two from the dipolarophile. Consequently, most of the interest in the electronic structure of 1,3-dipoles has been concentrated on the distribution of the four Jt electrons over the three heavy atom centres. Of course, a characteristic feature of this class of molecules is that it presents awkward problems for classical valence theories a conventional fashion of representing such systems invokes resonance between a number of zwitterionic and diradical structures [16-19]. Much has been written on the amount of diradical character, with widely differing estimates of the relative weights of the different bonding schemes. 

Cycloadditions are stereospecific cis additions, as has been shown in several cases using geometric isomers as dipolarophiles . In addition to the rigid structure of norbornene, as well-defined approach is preferred, namely the one that gives an exo adduct, as is shown in (a) above for azides, but also occurs with C-phenyl-N-methyl-nitrone and for diphenylnitrilimine -. The alternative approach of the reactants is sterically hindered in the case of norbornene the steric course of reactions of norbornadiene can be different, as was found using phenyl azide as the 1,3-dipole . 

It was demonstrated that the reaction proceeds without racemisation of the stereogenic phosphorus atom and with total selectivity towards the ( )-alke-nylphosphine oxide. Unexpectedly, it was also possible to dimerise phosphine oxide 109 (with R = Me) with 5% of 112b to obtain the corresponding optically pure ( )-diphosphine oxide in 85% yield. The crystal structure of this compound has been determined by X-ray diffraction and has been used as dipolarophile in 1,3-dipolar cycloadditions with nitrones, yielding several optically pure diphosphine oxides. Similar homometathesis reactions have been investigated in more detail by Grela, Pietrusiewicz, Butenschon and co-workers with other (racemic) substrates such as 109 and different catalysts. Gouverneur and co-workers studied a similar dimerisation of... 

In [3 + 2] cycloadditions of cyclic nitronates with mono-substituted dipolarophiles cjco-selectivity is generally favored, suggesting that steric interactions dominate the transition structure energy (Scheme 16.25 and Table 16.1) [121]. The ratio of the exo- and cn//o-products correlates with the size of the substiments on the dipolarophile bulkier... 

C(3a)/C(4) relationship arises from the dipolarophile approach proximal to C(4) substituent on the corresponding nitronate (Scheme 16.32). Only two- and three-atom tethered substrates have been studied in these cycloadditions. The two-atom tether leads to the fra/i5-C(3)/C(3a) relationship because it can only fold endo- during the [3 + 2] cycloaddition. However, the three-atom tether is flexible enough to react via the ejto-transition structure and to provide the cis-C (3)/C(3a) relationship. As always, the dipolarophile configuration is preserved as the relationship between C(2) and C(3) in the nitroso acetal. Unlike the double intermolecular cycloadditions or the spiro mode, the trans—trans or cis—trans relationship is established between the substiments at C(3),... 

In the first report [80], an unactivated Z-dienophUe attached to nitroalkene 379 undergoes an intramolecular [4 + 2] cycloaddition in the presence of SnCU to provide a mixture of stable, isolable nitronates 380 and 381 (Scheme 16.75). The major product 380 results from an exo-fold transition structure the minor product 381 forms via the endo-io A transition structure. Nitronate 380 participates in a [3 + 2] cycloaddition with 4-bromophenyl acrylate to afford nitroso acetal 383. The stereostructure of 383 (confirmed by single crystal X-ray structural analysis) reveals that the dipolarophile reacts with nitronate 380 in an exo fashion proximal to the C(4) substituent. This contrasteric result is interpreted in terms of a kinetic anomeric... 

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