Four-membered ring heterocycles azetidines

Only a few papers on the formation of compounds with small rings have been published. One example is the [2 + 2]-cycloaddition of electron-rich enamines to Schiff bases under high pressure (1.4 GPa) (87JOC365). The reaction leads to substituted azetidines (1). Four-membered ring heterocycles, thietane derivatives (4), are formed by interaction of sulfene (2) with enamines (3) (86CB257 93JOC3429). 

Four-membered Ring Nitrogen Heterocycles.— The synthesis of azetidine and its derivatives by akylation of an external or an internal amine is well known, and two more examples were reported in 1980. Interest in simple alkyl substituted azetidines now lies in studies on their stereo-preferences, and conversions to other important systems. That said, two photochemical investigations surprisingly turned up such systems as unexpected major products. Pete et while extending their work on 2-amino-cyclohex-2-enones examined the consequence of N-sulphonylation on their photochemical behaviour, and instead of getting aziridines as the principal products, they obtained azetidines (Scheme 35). These reactions were not as clean as the earlier ones, and aryl migration... 

Four-membered heterocycles prefer to cleave, upon ionization, into two fragments, each containing two of the ring atoms. Further cleavages commence from these initial fragments (Scheme 5). Specific details can be found as follows azetidines (B-71MS296), oxetanes... 

Azetidines are an interesting class of four-membered heterocyclic compounds, with various biological activities. These derivatives are difficult to synthetize due to ring strain. The allenylidene complex 43 has shown to be a useful substrate to generate this skeleton and to study its evolution into hexahydroquinoline [41]. Treatment of dichloromethane solutions of 43 with 1 equiv of dicyclohexylcarbodiimide at room temperature affords the iminiumazetidinylidenemethyl complex 111, which is isolated as a 4 1 mixture of the isomers Z and E shown in Eq. 5. 

Reviews on the following aspects of four-membered heterocycles have appeared 1,2-dioxetans and the reaction of singlet oxygen with alkenes/ /8-lactam antibiotics, small ring compounds of sulphur and selenium," recent developments in the synthesis of azetidines, the chemistry of benzazetes and of thiacyclobutenes (thietes) and their valence tautomers, and conformational barriers and interconversion pathways in some small ring systems. ... 

Not many drugs contain four-membered heterocycles either. The best-known drug containing an azetidine-ring is Schering-Plough s ezetimibe (Zetia). Launched in 2002 as a cholesterol absorption inhibitor, its mechanism of action is the inhibition of the Nieman-Pick Cl-like 1 (NPCl LI) protein. 

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