Azide-tethered ketones

A catalytic intramolecular Schmidt reaction of azide-tethered ketones... 

The first synthetically useful Schmidt reactions of alkyl azides with ketones were intramolecular. Thus, it was shown that azido-tethered ketones, when treated with Brpnsted or Lewis adds in CH2CI2 at room temperature, were converted to lactams in good to excellent yields (Table 7.1). Mono- and bicyclic ketones are attractive substrates for the preparation of fused bi- and tricyclic lactams and the range of ring sizes accommodated... 

Murphy and coworkers have also reported rearrangement reactions of azido-tethered epoxides in which the azide tether was attached directly to a phenyl-substituted epoxide. Thus, when they treated epoxide 36 with SnCLt at 0°C in THE, ketone 37 was isolated... 

A new intramolecular addition of aminyl radicals to carbonyl groups as a method to promote a ring expansion reaction leading to lactams has been described by Kim et al. In this reaction, the aminyl radicals are generated from azides which are tethered to the a-position of cyclic ketones by a two- or three-carbon chain. The addition of this A-radical to the carbonyl group generates an alkoxyl radical which is responsible for the ring expansion reaction (Eq. 32) [21a[. 

Sc(OTf)3 is also a useful promoter for the intramolecular Schmidt reaction of ketones and tethered azide reaction. This is typically catalyzed by Lewis acids and represents an efficient method for the generation of anfides and lactams (Equation (8.24)). Experiments carried out with this catalyst in water at high temperatures led to very good results [51]. 

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