Modifications of azetidin-2-ones

It is often necessary to prepare /3-lactams with particular substituents at N-1, C-3 and C-4, e.g. in the preparation of fused /3-lactams from monocyclic precursors. For reasons of space it is not possible to give an exhaustive list of the variously substituted /3-lactams available however, Table 4 summarizes the most general routes to /3-lactams bearing particular substituents at C-3 and C-4. -Substitution of azetidin-2-ones has already been dealt with cf. Section 5.09.3.2.3). N-Unsubstituted /3-lactams and protected 3-amino-/3-lactams are particularly important synthetic intermediates and methods of preparing these are discussed below. 

AT-Unsubstituted azetidin-2-ones are versatile intermediates in the preparation of a variety of novel /3-lactam containing systems. They are usually made either by reductive dechlorosulfonylation of alkene/chlorosulfonyl isocyanate cycloadducts cf. Section 5.09.3.3.2), which 

As many natural and synthetic /3-lactams bear 3-acylamino substituents, the corresponding free amines or protected forms thereof are versatile synthetic intermediates. They may be prepared in several ways, for example by deacylation of the 7-amido group in naturally occurring penicillins by enzymic or chemical means. Chemical degradation usually involves conversion of the amide to a chloroimidate followed by cleavage with aqueous alcohols (75S547 p. 560, 78T1731 p. 1753). 

A third approach to 3-amino-/3-lactams is by Curtius rearrangement of the corresponding acyl azides. These are readily prepared from r-butyl carbazides, available via photochemical ring contraction of 3-diazopyrrolidine-2,4-diones in the presence of f-butyl carbazate (c/. Section 5.09.3.3.2). Thus treatment of (201) with trifluoroacetic acid followed by diazotiz-ation gives the acyl azide (202) which, in thermolysis in benzene and subsequent interception of the resulting isocyanate with r-butanol, yields the protected 3-amino-/3-lactam (203) (73JCS(P1)2907). 

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