Five-membered ring heterocycles lactams

Five-membered ring heterocyclic compoxmds containing nitrogen are one of the most common heterocycles. In fact, the synthesis of a great variety of that such as pyrrole, pyrazole, imidazole, triazole, tetrazole, lactams, and imides involving porous catalytic systems have been investigated. 

Cyclic esters and amides are called lactones and lactams, respectively. The ring size of the heterocycle is indicated by a Greek letter. An amide in a four-membered ring is called a P-lactam, because the P carbon to the carbonyl is bonded to the heteroatom. An ester in a five-membered ring is called a y-lactone. 

Most heterocycles have the same chemistry as their open-chain counterparts. Lactones and acyclic esters behave similarly, lactams and acyclic amides behave similarly, and cyclic and acyclic ethers behave similarly. In certain cases, however, particularly when the ring is unsaturated, heterocycles have unique and interesting properties. Let s look first at the five-membered unsaturated heterocycles. 

Penicillins are the most widely used of the clinical antibiotics. They contain in their structures an unusual fused ring system in which a four-membered P-lactam ring is fused onto a five-membered thiazolidine. Both rings are heterocyclic, and one of the ring fusion atoms is nitrogen. These heteroatoms do not alter our understanding of molecular shape, since we can consider that they also have an essentially tetrahedral array of bonds or lone pair electrons (see Section 2.6.3). 

A variety of methods are available for the synthesis of heterocyclic carbonyl compounds by radical cyclization. For example, the cyclization of alkoxycarbonyl radicals is particularly useful for the synthesis of five- and six-membered ring lactones [80]. Recent applications of this cyclization method include Zard s photoly-tical transformation of an alkoxycarbonyl dithiocarbonate having a double bond which can serve as a key step in the synthesis of ( )-cinnamolide and RA. Evans s enantioselective synthesis of 4-hydroxy butenolide terminus, which is applicable to the synthesis of mucocin [81J. Amidyl radical cyclizations are frequently utilized for the synthesis of five- and six-membered ring lactams [82]. However, this section only focuses on recent methods for heterocyclic carbonyl compounds by an n-i-1 type strategy based on radical carbonylations. 

Lukes and coworkers " developed a very simple and useful method for the preparation of heterocyclic enamines. A-M ethyl lactams with five- and six-membered rings (104, n = 1,2) give, with Grignard reagents, l-methyl-2-alkyI(aryl)-2-pyrrolines (105, n = 1) and l-methyl-2-alkyl(aryl)-2-piperideines (105, n = 2), respectively. 2,2-Dialky-lated bases (106, n = 1,2) are by-products of this reaction. Aromatic Grignard reagents afford only the unsaturated bases, probably because of steric factors " ". Some authors who repeated the reactions isolated only pyrrolines or, in other cases, 2,2-dialkylated bases . This can be ascribed to the use of unsuitable isolation technique by the authors. The reaction was also carried out with various substituted and non-methylated lactams . ... 

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