Azepines and derivatives

Detailed computational studies have been reported on 5-azatropolone and 17/-azepine-4,5-dione and related isoelectronic homologues and isomers 06JPC(A)1600 . 

A novel electrophilic reaction of the 2-methoxyazepinium ion 2, formed in situ from 1 on treatment with TiCl4,was observed in the presence of benzene to give 3, 4 and 5. The kinetics of the isomerisation (ki k2, k3) of the 477-azepine 3 to 8 via 6 and 7 were also reported 06EJ03803 . 

Satake et al. reported further detailed studies on the chemistry of 2//-azepines highlighting a [1,5] sigmatropic hydrogen shift and also an unusual [1,5] sigmatropic propylthio shift on heating 9 to afford 10 and 11 respectively kinetic measurements were consistent with a 

Inclusion of the amide in oxazolidinone functionality can be used to overcome diene statial disposition issues, for example in the conversion of 19 into 20 yields of 20 were generally high (Table 2). Ring opening of the oxazolidine moiety with or without loss of the mandelic acid moiety then afforded the corresponding azepin-2-ones 06TL3625 . 

Other -substituted and reduced 2-azepinone derivatives 22 can also be accessed in high yields (Table 3) by ring closing metathesis on the precursors 21 using Grubbs II catalyst 18. A variety of IV-heteroaryl substitutent groups were tolerated in this reaction 06TL3295 . 

The synthetic power of Ru-catalysed ring closing metathesis reactions has continued to be realized, for example, in the synthesis of the azepine derivative 4 from 3, which was prepared in turn from 1 via 2. Reduction of 4 afforded the azepane 1 05SL631 . 

Similarly, the chiral keto acid 12 was obtained in good yield from ring closing metathesis on 10 compound 10 was obtained via 8 and 9 from 2, while the acid 12 resulted from hydrolysis of the initial RCM product 11. Hydrogenation of the double bond in 12 then afforded the azepane 13 in good yield 05SL631 . 

An azepanone-based inhibitor 22 of cathepsin K, a cysteine protease inhibitor, was accessed via an asymmetric synthesis from 14 and 15, with ring closing metathesis of 16 then being used to complete the 7-membered ring in the intermediate 17 with a veiy high de. 

Further functional group manipulations via 18-21 then revealed the inhibitor 22 

Another route to azepinones involving substituted allenes such as 31 gave 32 in high yield on Boc-group removal and then heating the resultant amine in acetonitrile at reflux 

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SEVEN-MEMBERED SYSTEMS CONTAINING ONE HETEROATOM 7.2.1 Azepines and derivatives... 

Amino-3H-azepine (and derivatives, depending on the amine present) is believed to originate from an azacyclopropene intermediate °, viz. 

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