In the last few years we have been interested in the dipolar cycloaddition of nitrones with diiron acyl complexes. [1, This chemistry has been shown to be effective in the diastereo-and enantioselective addition of a variety of nitrones to mono-and disubstituted a,b-unsaturated acyl complexes. It was found that, after cycloaddition, oxidation of the resultant complex gives a thioester isoxazolidine product. [1±3] It has been shown that isoxazolidines can be converted to amino alcohols through reduction of the NÀO bond. [4±6] In the case of the cycloadducts discussed below, this results in the formation of thioester derivatives of b-amino acids. Here in we show that reaction of a cyclic nitrone derived from proline proceeds with one enantiomer of the diiron complex significantly faster than with the other enantiomer. Additionally the utility of this approach is demonstrated through the synthesis of a simple carbapenem.
Reaction of complex 1 with the Z-nitrone 2 gave the expected isoxazolidine product, which could be oxidized to the corresponding thioester 4. Reaction with zinc and acetic acid then yielded the b-amino b-hydroxy thioester 5. The hope was that treatment of the thioester with mercury trifluoroacetate would result in removal of the sulfur with commensurate trapping by the amine group to give the b-lactam. [7±9] Since optically active diiron acyl complexes are accessible, this approach would potentially provide a mild route to optically active b-lactams. Unfortunately the initial attempt to form the b-lactam from amino alcohol 5 resulted in less than a 15 % yield of the desired product 6. It has been reported that the cyclization to give b-lactams with groups cis on the adjacent carbon atoms of the four-membered ring is difficult (Scheme 1). [10] Because of this observation, and the fact that a large number of the known b-lactam antibiotics possess the opposite stereochemistry, the dipolar cycloaddition was run on an E-nitrone. The stereochemistry of acyclic nitrones is typically Z. Consequently, it was necessary to attempt the cyclization with a cyclic nitrone. Endo addition of such a nitrone would give a b-amino acid with the correct stereochemistry to readily form a b-lactam. Cyclization of nitrone 7 with diiron complex 1 followed by oxidative removal of the 72 %) or 5 (1.30 g, 87 %). Recrystallization from hexane yielded very fine needles of both compounds.
Crystal data for 5: C 84 H 126 N 12 OSn 4 , M r 1794.73, monoclinic, space group P2 1 /c (no. 14), a 22.911(4), b 18.441(6), c 22.250(13) , b 115.30(3)8, V 8499(6) 3 , F(000) 3688; Z 4, 1 calcd 1.40 g cm À3 , m(Mo Ka ) 14.2 cm À1 , crystal dimensions 0.3 Â 0.2 Â 0.1 mm, 12 145 reflections collected for 2 q 238, 11 805 independent reflections, R1 0.047 for 8396 reflections with I b 2 s(I), wR2 0.09 (for all data), S 0.989. Data collected at T 173(2) K, Enraf Nonius CAD-4 diffractometer, absorption correction, structural solution by direct methods, full-matrix least-squares refinement on F 2 with SHELXL-93 with non-hydrogen atoms anisotropic. The asymmetric unit contains two independent molecules of the Sn 2 complex and one molecule of diethyl ether solvent.