Nitronates diastereoselectivity, chiral dipoles

Extensive studies on diastereoselectivity in the reactions of 1,3-dipoles such as nitrile oxides and nitrones have been carried out over the last 10 years. In contrast, very little work was done on the reactions of nitrile imines with chiral alkenes until the end of the 1990s and very few enantiomerically pure nitrile imines were generated. The greatest degree of selectivity so far has been achieved in cycloadditions to the Fischer chromium carbene complexes (201) to give, initially, the pyrazohne complexes 202 and 203 (111,112). These products proved to be rather unstable and were oxidized in situ with pyridine N-oxide to give predominantly the (4R,5S) product 204 in moderate yield (35-73%). 

Most of the approaches outlined in Figure 15.10 have been successfully realized on insoluble supports, either with the alkene or alkyne linked to the support, or with support-bound 1,3-dipoles (Table 15.16). Nitrile oxides are highly reactive 1,3-dipoles and react smoothly with both electron-poor and electron-rich alkenes, including enol ethers [200]. The addition of resin-bound nitrile oxides to alkenes (Entries 5 and 6, Table 15.16) has also been accomplished enantioselectively under catalysis by diisopropyl tartrate and EtMgBr [201], The diastereoselectivity of the addition of nitrile oxides and nitrones to resin-bound chiral acrylates has been investigated [202], Intramolecular 1,3-dipolar cycloadditions of nitrile oxides and nitrones to alkenes have been used to prepare polycyclic isoxazolidines on solid phase (Entries 7 and 9, Table 15.16). 

The 1,3-dipolar cycloaddition of a variety of nitrile oxides, nitrones, ethyl diazoacetate, and azomethine ylide to the chiral furanone 174a was studied with respect to the present regio- and diastereoselectivity (93T8899). In the case of the azomethine ylide addition, three stereoisomeric adducts were obtained. However, in the case of the other dipoles only two stereoisomeric adducts were isolated the major product proved to be the an//-facial isomer. In this way, a number of multifunctional (lactone-annulated) isoxazolines 241 and 242, isoxazolidines 243 and 244, pyrazolines 245a,b, and pyrrolidines 248a,b,c could be synthesized (Scheme 65) (93T8899). 

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