Synthesis of cis-4,5-Diarylazepanes

Abstract

Substituted cis-4,5-diarylazepanes are synthesized in modest overall yields starting from 5,5-diarylazepan-4-ones by a ­reduction, mesylation, rearrangement, and hydrogenation reaction sequence.

Key words

cis-4,5-diarylazepanes - boron trifluoride etherate - heterocycles - 1,2-sigmatropic shift - spiro compounds

References and Notes

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9

Representative Procedure for Skeleton 5
BF₃˙OEt₂ (1.0 mmol) was added to a stirring solution of the skeleton 4 (0.5 mmol) in CH₂Cl₂ (10 mL) at r.t. The reaction mixture was stirred at reflux for 40 h. The total procedure was monitored by TLC until the reaction was completed.
A sat. NaHCO₃ solution (1 mL) was added to the reaction mixture, and the solvent was concentrated under reduced pressure. The residue was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford crude product under reduced pressure. Purification on silica gel (hexane-EtOAc = 8:1 to 4:1) afforded skeleton 5.

10

CCDC 810260 (5b), 810167 (5e), 805710 (7b), and 817429 (8b) contain the supplementary crystallographic data for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; e-mail: [e-mail]].

11

Representative Procedure for Skeleton 7
Et₃N (500 mg, 5.0 mmol), skeleton 2 (1.0 mmol), and CH₂Cl₂ (6 mL) were added to a sealed tube at r.t. The reaction mixture was stirred at reflux temperature for 25 h and then cooled to r.t. CH₂Cl₂ (10 mL) was added to the reaction mixture, and then HCl solution (1 N, 10 mL) was also added to the reaction mixture. The reaction mixture was extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were washed with brine, dried, filtered, and eva-porated to afford crude product. Purification on silica gel (hexane-EtOAc = 4:1 to 2:1) afforded skeleton 7.

16

Representative Procedure for Skeleton 8
Skeleton 5 (0.13 mmol) was dissolved in EtOAc (10 mL; free of oxygen) and was irradiated under a nitrogen atmosphere with a lamp (λ = 3060 Å), using a Pyrex glass filter at r.t. for 80 h. The solvent was evaporated to afford crude product. Purification on silica gel (hexane-EtOAc = 4:1 to 2:1) afforded skeleton 8.