Fig. 8: Late-stage diversification of 4a and 2a.
From: Divergent synthesis of benzazepines and bridged polycycloalkanones via dearomative rearrangement
Selective olefination and reduction of the dione to give 5 and 6. Reductive acetalation companied with entirely reduction of the diene to afford the cage product 7. Luche reduction conditions could also produce the cage product 8 with the cyclohexadiene partially hydrogenated. The bridged carbonyl group could be reduced with lithium aluminium hydride to furnish 9. One C = C double bond of the cyclohexadiene was selectively reduced by Hantzsch ester to provide 10. Epoxidation product 11 was obtained with m-CPBA. Kinetically oxidation of the imine moiety to give nitrone 12. Retro Michael addition to give the fragmentation oxindole 13, which could transform to the spiral dione 14. Under the acidic deprotection conditions the three-dimensional architecture of 4z collapsed entirely to form a unique [6-6-5-6] tetracyclic architecture 15. Furthermore, the benzoyl functionality could be easily installed on free nitrogen atom of 2a to give product 16. Interestingly, compound 2a has been structurally reorganized into a [6-7-5] tricyclic architecture 17 by refluxing in TsOH/methanol solution. m-CPBA = m-chloroperoxybenzoic acid. TEA = triethylamine. TFA = trifluoroacetic Acid. DMAP = 4-(dimethylamino)pyridine. Ms = methylsulfonyl. Ts = p-toluenesulfonyl. Boc = t-butoxycarbonyl. NaBH4 = sodium borohydride. LiAlH4 = lithium aluminum hydride.
