Synthesis of 4,4′-Disubstituted Azepines via Ring-Closing Metathesis Reaction and Asymmetric Arylation of Lactones

Abstract

The syntheses of the title compounds were accomplished via an original sequence of reactions including the ring-closing metathesis­ of ω-dienes by using the second-generation Grubbs’ catalyst. The chiral diene precursors are available in racemic or optically enriched form from the corresponding α,α′-disubstituted lactones derivatives

Key words

heterocycles - ring closure - metathesis - butyrolactone - arylation

References

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1

Current address: J&J PRD, Turnhoutseweg 30, 2340 Beerse, Belgium.

2

A search in the mddr-3d Isis database produced >1000 hits of azepine derivatives in various stages of development.

6

With the exception of compounds 9 (unstable), all isolated compounds in this work gave satisfactory ¹H and ¹³C NMR spectra and HRMS or favorable comparison with the literature data.

11

Compounds 4a and 4b and their subsequent derivatives are volatile and were not isolated. Overall yields are reported for 9a and 9b.

16

Tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][benzylidine]ruthenium (IV) dichloride: CAS number [246047-72-3].