Lactams asymmetric reactions, 1,3-dipolar

Whereas there are numerous examples of the application of the products from diastereoselective 1,3-dipolar cycloaddition reaction in synthesis [7, 8], there are only very few examples on the application of the products from metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction in the synthesis of potential target molecules. The reason for this may be due to the fact that most metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction have been carried out on model systems that have not been optimized for further derivatization. One exception of this is the synthesis of a / -lactam by Kobayashi and Kawamura [84]. The isoxazoli-dine endo-21h, which was obtained in 96% ee from the Yb(OTf)3-BINOL-catalyzed... 

The phosporic acid (261) catalysed three component reaction involving asymmetric 1,3-dipolar cycloaddition of electron-deficient azomethine ylides (327), aromatic aldehydes (328) and 2-aminomalonates (329) to provide to novel 2,5-dihydropyrrole derivatives (330) with potential bioactivities with enantioselectivities of up to >99% ee (Scheme 86). The Bronsted acids (253) catalysed intermolecular enantioselective alkylation of indoles (332) with cx,p-unsaturated y-lactams (331) thus providing a highly enantioselective method for the synthesis of chiral pyrroli-dinones (333) containing indole moieties, with enantioselectivity (up to 95% ee), has been described by Huang et al. (Scheme 87). " ... 

Denmark advanced a strategy that involves tandem cycloaddition sequences with nitronates for the asymmetric synthesis of alkaloids [73, 74). A camphor-derived auxiliary permits the preparation of chiral enol ethers (cf. 68) as the reacting partners. A noteworthy example of the complex structures that could be generated by use of 68 is illustrated in Scheme 18.15. A hetero-Diels-Alder reaction between 68 and nitronate 67 generated 69 as a 96 4 mixture of endo/exo diastereomers. The adduct then participated in an intramolecular dipolar cycloaddition at elevated temperatures to yield cycloadduct 70 as a single diastereomer (90%). The tricyclic target 72 was obtained in 88 % yield after reductive removal of the chiral auxiliary and lactam formation [74]. 

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