7-Azabicyclo heptenes

Although pyrroles do not generally participate in Diels-Alder reactions with olefinic dienophiles, the very reactive hexafluoro-Dewar benzene with pyrrole gives the 1 1 and 1 2 adducts, 27 and 28, both of which probably have all-ea o stereochemistry. Some other 7-azabicyclo-heptene derivatives have been obtained via cycloaddition reactions of 7-azaquadricyclanes (see Section II, F). 

Azabicyclop.2.0]heptane circular dichroism, 7, 356 nomenclature, 7, 342 7-Azabi cyclop. 1.0]heptane synthesis, 7, 85-86 3-Azabicyclo[4.1.0]heptene, 7, 544 2-Azabicyclop.2.0]hept-6-en-3-one synthesis... 

Benz-7-azabicyclo[2.2.1]heptenes in isoindole synthesis, 4, 351 Benz[e][l, 2]azaborine, 2-chloro-1,2-dihydro-synthesis, 1, 647... 

As expected, similar treatment of 2-substituted 1,4-dihydrobenzenes, e.g. 17, gives rise to two isomeric azabicyclo[4.1.0]heptenes, e.g. 18 and 20, which, in turn, yield the corresponding isomeric 1//-azepines, e.g. 19 and 21.61... 

A reductive intermolecular Heck heteroarylation (hydroheteroarylation) of A-protected azabicyclo[2,2,l]heptene 165 has been used to construct 7-azabicyclo[2.2.1]heptane 166 in moderate yield [131, 132]. An asymmetric version of such a transformation to provide enantiomerically-enriched iV-protected epibatidine has also been described [128, 133]. It was found that introduction of Noyori s BINAP ligand resulted in the best enantioselectivities with 72-81% ee and a 53% yield. By using either the (R)- or (S)-BINAP ligand, either enantiomer was easily accessible. 

Recently, Malpass et al. reported a synthesis of epibatidine isomers also under reductive Heck conditions [134, 135]. 2-Azabicyclo[2.2.1]heptene 167 was assembled by cycloaddition of an iminium salt with cyclopentadiene. Treatment of 167 with 2-chloro-5-iodopyridine provided a mixture of exo-5-(6-chloro-3-pyridyl) derivative 168 and exo-6-(6-chloro-3-pyridyl) derivative 169. 

Saponification of the diester (47) gave the hydroxyacid (48) along with its dehydration product, the 7-azabicyclo[2.2.1]heptene (49). 

The 7-azabicyclo[2.2.1]heptene derivative (57) decomposes in hot aqueous sodium carbonate solution to give A-benzylpyrrole-3,4-dicarboxylic acid and, presumably, ethylene. Furan-3,4-dicarboxylic acid derivatives are formed analogously on heating the 7-oxabicyclo-[2.2.1]heptene diesters (58). The only thermal decomposition of a... 

When toluene solutions of 2-azabicyclo[3.2.0]hepten-4-ones were heated between 120-200°C in sealed tubes, a [1,3] shift of Cl and an ensuing decarbonylation produced dihydropyridines 220,21,130,133 an(j 3 132 either ri or r2 were vinyl groups, other [1,3] or [3,3] shifts competed successfully with dihydropyridine formation (see Sections 2.4.3.1. and 2.4.4.). The proposed intermediates of this reaction, e.g. 2-azabicyclo[2.2.1]heptenes 4 and 5 were isolated in the thermolysis of the related 3-ethoxy-2-azabicyclo[3.2.0]heptenes20-130,131,133 in toluene between 140-180°C. 

Under certain circumstances, the conjugate addition and cycloaddition reaction pathways overlap for a,P-unsaturated electrophiles. For example, when the 2,5-dimethylpyrrole complex 22 is combined with 1 equiv of MVK in acetonitrile, a 1 1 ratio of the p-alkylated 3//-pyrrole complex 96 and the a-alkylated 2Z/-pyrrole complex 98 is isolated (Figure 18). When the reaction is monitored by H NMR in CD3CN, an intermediate 7-azabicyclo[2.2.1]heptene complex (97) is observed at early reaction times, and eventually converts (tm 1 h) to compound 98 via a retro-Mannich reaction followed by proton transfer. 

Patent 7-Azabicyclo[2.2.1]Heptane and Heptene Derivatives as Cholinergic... 

The thermal, photochemical and Lewis acid catalysed dissociations of di-azabicyclo[2.2.1]heptenes with side chains of various lengths terminated by aldehyde groups 143 have also been examined [119] (Scheme 31). The course of the reaction depended on the length of the tether. For the precursor with n = 1, tetrahydroindenol 144 was the main isolated product. Thermolysis of... 

Treatment of the azabicyclo[2.2.1]heptene 580 with MCPBA for 3-5 s generated the oxabicyclo[3.2.1]octene 582 via a rapid Meisenheimer rearrangement of the A -oxide 581. Compound 582 was converted into the thermodynamically more stable isomeric bicyclic isoxazolidine 583 by simple heating (Scheme 142) <2000CC2451>. 

Hodgson, D.M., Maxwell, C.R., Matthews, I.R., 1998. An epoxide rearrangement. Radical rearrangement approach to 6-substituted 2-azabicyclo[2.2.1]-5-heptenes. Synthesis of an epibatidine analog. Syn-lett., 1349-1350. 

The discovery of the structure of 7-azabicyclo[2.2.2]heptene isolated from the Ecuadorian poison frog, Epipedobates tricolor [39], has caused a rebirth of investigation of Diels-Alder reactions with pyrrole as a diene [40]. Subsequently, a large number of 7-azabicyclo[2.2.1]-heptane and 7-azabicyclo[2.2.1]hept-2-ene derivatives have been synthesized and protected by patents [41]. We have... 

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