In 1972 Kinugasa and Hashimoto reported a convergent route to β-lactams through the reaction between copper phenyl acetylides and nitrones.[1] Four years later, Ding and Irwin[2] proposed the mechanism of the Kinugasa reaction, which involved the 1,3-dipolar cycloaddition and subsequent rearrangement of the intermediate isoxazoline. In following years, the extended asymmetric versions of the Kinugasa reaction have been proposed by groups of Basak[3] and Fu.[4]

Very recently, we reported a diastereoselective version of the Kinugasa reaction involving nonracemic cyclic nitrones and simple achiral/chiral acetylenes.[5] Such reactions displayed high diastereoselectivity leading to one dominant product. On the basis of the proposed stereochemical model of the reaction, it has been shown that the stereochemical outcome of the Kinugasa reaction depends on the first step, 1,3-dipolar cycloaddition. The addition is controlled by the substituent present in the nitrone, whereas the protonation of intermediate enolate in the second step occurs from the less shielded side of carbapenam skeleton.

The lecture will be devoted to a detailed discussion of this methodology and practical application of developed methodology will also be presented.

[1]  Kinugasa, M.; Hashimoto, S. J. Chem. Soc., Chem. Commun. 1972, 466.

[2] Ding, L. K.; Irwin, W. J. J. Chem. Soc., Perkin Trans. 1 1976, 2382.

[3] Basak, A.; Mahato, T.; Bhattacharya, G.; Mukherje, B. Tetrahedron Lett. 1997, 38, 643.

[4] Lo, M.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 4572.

[5](a) Stecko, S.; Mames, A.; Furman, B.; Chmielewski, M. J. Org. Chem. 2008, 73, 7402. (b) Mames, A.; Stecko, S.; Mikołajczyk, P.; Soluch, M.; Furman, B.; Chmielewski, M. J.Org. Chem. 2010, 75, 7580. (c) Michalak, M.; Stodulski, M.; Stecko, S.; Mames, A.; Soluch, M.; Panfil, I.; Furman, B.; Chmielewski, M. J. Org. Chem. 2011, 76, 6931.

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