Azabicyclo octadienes

To Diazabicyclo[3.3.0]octadienes, Diazabicyclo 3.2.1 octadienes, and 2-Azabicyclo 3.2.1]octenes... 

Derivatives of 1,2-dihydroazocine are potentially available by valence isomerization of the 7-azabicyclo[4.2.0]octadiene system. Sulfonyl derivatives (71) of the latter have been prepared, but the equilibria with dihydroazocines lie completely on the side of the bicyclic isomers (71JOC435). On heating, the bicyclooctadienes rearrange to the acyclic tetraenes (73), presumably via the unstable dihydroazocines (72). 

Rhodinm-catalysed addition of a vinyl carbene prodnces a cyclopropanated intermediate that undergoes a Cope rearrangement, neatly producing an 8-azabicyclo[3.2.1]octadiene - the ring skeleton of cocaine." ... 

Yet another extension of this type of procedure utilizes cyclobutadienes (198 R = Me, or Bu ) as the alkene component. These react with A-acylimines to form azaoxabicyclo[4.2.0]octadienes (199) and azabicyclo[2.2.0]hexenes (200). When exposed to acid the latter products rearrange into the former (Scheme 54) <85TL3315>. 

An intramolecular variant of this synthetic methodology has been developed. Pyrrole-linked vinyldiazomethanes (217) undergo rhodium-catalysed carbene formation and intramolecular insertion to give moderate yields of fused azetidines (218) of the 7-azabicyclo[4.2.0]octadiene type (Equation (65)) <94TL5209>. 

The pentacyclic alkaloid ( )-meloscine (134) was prepared by Feldman and Antohne using a clever allenyl azide cycloaddition/cyclization cascade to deliver the core azabicyclo[3.3.0]octadiene substructure (2012OL934). Strain-driven release of nitrogen from the dipolar cycloadduct 129 derived from 128 promotes formation of the azatrimethyl-enemethane diradical 130 en route to the bicyclic product 131 (Scheme 30). For the synthesis ofmelo-scine 134, the thermolysis of a dilute solution of allene 132 in toluene gave the desired bicycle 133 whose structure was estabfrshed by single crystal X-ray analysis. Subsequent manipulation of the peripheral functionality in 133 then delivered ( )-meloscine 134. 

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