Synthesis of β-lactam-4-ylidenes and their application as synthons for novel β-lactam synthetic methodologies

Abstract

<p>The first portion of this thesis deals with the chemistry of the imino-triazoline, imino-thiadiazoline, and imino-oxadiazoline systems. All three systems have the cyclic cis azo function as a common feature, but it was found that each system has its own characteristic chemistry. Upon quaternization of the sp² ring carbon the stability of the resulting cyclic azo compounds increased in the following order: triazolines < thiadiazolines < oxadiazolines. Thus, the reaction of the imino-triazoline with benzoylcyanide formed the aziridine. Moreover, the imino-triazoline system did not form a stable spiro-β-lactam triazoline when treated with diphenylketene. On the other hand, the quaternization of the imino-thiadiazoline sp² ring carbon did not always lead to N₂ extrusion. The reaction of the imino-thiadiazoline with diphenylketene led to N₂ extrusion followed by electrocyclic ring closure to form the spiro-β-lactam thiirane as the only product, if the substituent on nitrogen was a phenyl group. Replacing the phenyl group on nitrogen by a benzyl group led to the isolation of both the spiro-β-lactam thiadiazoline and the product of N₂ extrusion, the corresponding spiro-β-lactam thiirane. The spiro-β-lactam thiadiazoline loses N₂ thermally to form the thiirane as the only product. The chemistry of the oxadiazoline system was very different. Imino-oxadiazolines reacted with different substituted ketenes to form the corresponding spiro-β-lactam oxadiazolines. Quaternization of the sp² ring carbon did not lead to N₂ extrusion; the spiro-β-lactam oxadiazoline system (172) was very stable at room temperature. The thermolysis of the spiro-β-lactam oxadiazoline system (172) at 100°C gave products derived from the novel β-lactam-4-ylidene (181), as an intermediate. Product analysis implied the generation of the carbene 181 quantitatively. [Image Removed] The second portion of this thesis deals with a study on the scope of the spiro-β-lactam oxadiazoline system (172), as a source for β-lactam-4-ylidenes (181). This oxadiazoline system (172) proved to be an excellent source for the β-lactam-4-ylidene (181), in the sense that it is a mild, bottleable, and a quantitative source. On the other hand, the chemistry and scope of the novel β-lactam-4-ylidene (181) were studied. The β-lactam-4-ylidenes (181) were trapped inter- and intra-molecularly by insertion and addition reactions. Carbene trapping experiments were carried out to form the novel spiro-β-lactam cyclopropenes, spiro-β-lactam cyclopropanes, various carbene insertion products and fused bicyclic β-lactams. Thus, the β-lactam-4-ylidene (181) proved to be an excellent synthon for novel β-lactam systems that could not be synthesized, in a single step, otherwise.</p>