Bridge lactams

An enamine was obtained in the synthesis of coronaridine (648) by aluminum hydride reduction of a bridged lactam, followed by dehydration on alumina. Additional examples of enamine formation by reduction of enamides (649) and thioenamides (650) were reported. 

Fig. 10 Aztreonam (18), bridged lactam (19a), bridged sulfactam (19b), and oxamazin (19c)...

A novel route to ( )-0-methylthalisopavine (26) involves the oxidation of the properly substituted tetrahydro-3-isoquinolone of type 129 with vanadium oxy-trifluoride to furnish bridged lactam 130. Compound 130 was then reduced to the racemic isopavine alkaloid 26 in an overall yield of 4.4% (Scheme 26) 136). 

The method is useful for synthesis of five-, six- and seven-membered lactams, but not of P-lactams or macrolactams. The bridged lactam 2 was obtained from 1 in 77% yield by reaction with di-n-butyltin oxide. 

Bridge lactams. 5.25 g. 10,ll-dihydro-5,10-epoxymethano-5H-dibenzo[a,d]cyclo-hepten-12-one added to hydroxylamine (prepared from the hydrodiloride with NaOH in water) in ethylene glycol-water, refluxed 13 hrs., and kept 4 days at 100° -> 3.75 g. 13-hydroxy-10,ll-dihydro-5,10-iminomethano-5H-dibenzo[a,d]-cyclohepten-12-one, 19.5 g. hydrogenated 1.5 hrs. at 70° with Raney-Ni in ethanol 15 g. 10, ll-dihydro-5,10-iminomethano-5H-dibenzo[a,d]cyclohepten-12-one. G. N. Walker et al., J. Org. Chem. 5(5, 466 (1971). 

Szostak, M., Aube, J. Medium-bridged lactams a new class of non-planar amides. Org. Biomol. Chem., 2011, 9,... 

Chemistry of bridged lactams and related heterocycles 13CRV5701. Copper-catalyzed synthesis of N-heterocyclic compounds 12S2805. The cyanamide moiety, synthesis, and reactivity, in particular, formation of N-heterocycles 12S1279. 

The intramolecular Schmidt reaction has provided a solution to the problem of bridgehead lactam synthesis. The bridged lactams incorporate a twisted amide unable to achieve standard planar geometry and can undergo rapid hydrolysis. Reaction of ketoazide with HBF4 in ether results in a mixture of two latams from which the desired quinoclidone 92 is isolated in 38% yield after recrystalization. ... 

Bridge lactams 23, 689 26,351 Bridges s. a. Compds., double-bridged, Etheno bridges, Methano..., Methylene bridge... 

The reaction of trienyl azide 76 was noteworthy as the first reported example of a combined Diels-Alder/Schmidt reaction of any type (see Section 7.7 above). In addition, the isolation of compound 77b represented the first known observation of a bridged lactam from an intramolecular Schmidt reaction (in contrast to the formation of bridged ortho-amide 62 shown in Scheme 7.40). Mechanistically, an endo Diels-Alder leads to 77a and 77b (box at bottom of Scheme 7.43), while an exo transition state leads to 77c (transition state not shown). The formation of fused or bridged lactam depends on antiperiplanar migration of carbon from the equatorially or axially disposed N2 groups in the intermediates shown. 

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