Exploring the Chemistry of [2.2.2]Paracyclophane^[1]

Abstract

Starting with the parent compound [2.2.2]paracyclophane several routes were developed to synthesize its 4-vinyl derivative. From the 4-aldehyde and the bromomethyl derivative the stilbenophanes were prepared which photocyclize to the phenanthrenophanes. A new route to a bridged ketone was developed which was subjected to the addition of phenyllithium and to typical aromatic substitution reactions (inter alia Rieche formylation, Friedel–Crafts acylation). Bromination of the bridged ketone yielded an unusual tropone derivative. Electrophilic substitution reactions were also carried out for the bridged hydrocarbon, the reduction product of the bridged ketone. For both the bridged ketone and the bridged hydrocarbon the electrophilic substitutions occur regioselectively, favoring the introduction of the new substituent in a syn orientation to the bridging keto and methylene group, respectively.

1 Introduction

2 Results and Discussion

2.1 4-Vinyl[2.2.2]paracyclophane (5)

2.2 [2.2.2]Paracyclophane (2a) as Part of Extended Aromatic Systems

2.3 The Preparation of 5,12-Methano[2.2.2]paracyclophan-25-one (3)

2.4 Selected Reactions with 5,12-Methano[2.2.2]paracyclophan-25-one (3)

2.4.1 Reactions of 3 with Metalorganic Reagents

2.4.2 Friedel–Crafts Reactions with 3

2.4.3 Bromination of 3

2.5 Selected Reactions with 5,12-Methano[2.2.2]paracyclophane (31)

2.5.1 Friedel–Crafts Reactions

2.5.2 Bromination of 31

3 Conclusion

Key words

cyclophanes - electrophilic aromatic substitution - bromination - Rieche formylation - Friedel–Crafts acylation - photocyclization - ­McMurry coupling

• References and Notes

• 1 Paracyclophanes, Part 74; for Part 73, see: Hopf H, Dix I, Jones PG. Z. Naturforsch., B 2015; 70: 573
• 2 Baker W, McOmie JF. W, Norman JM. J. Chem. Soc. 1951; 1114
• 3 Tabushi I, Yamada H, Yoshida Z, Oda R. Tetrahedron 1971; 27: 4845
• 4 Tabushi I, Yamada H, Kuroda Y. J. Org. Chem. 1975; 40: 1946
• 5 Vögtle F, Kißener W. Chem. Ber. 1984; 117: 2538
• 6 Schmidbaur H, Hager R, Huber B, Müller G. Chem. Ber. 1988; 121: 1341
• 7 Brown CJ, Farthing AC. Nature (London, U.K.) 1949; 164: 915
• 8 Cohen-Addad C, Baret P, Chautemps P, Pierre J.-L. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1983; 39: 1346
• 9 Renault A, Cohen-Addad C. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1985; 41: 773
• 10 Jones PG, Bubenitschek P, Heirtzler F, Hopf H. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1996; 52: 1380
• 11 Jones PG, Heirtzler F, Hopf H. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1996; 52: 1384
• 12 Kang HC, Hanson AW, Eaton B, Boekelheide V. J. Am. Chem. Soc. 1985; 107: 1979
• 13 Schmidbaur H, Hager R, Huber B, Müller G. Angew. Chem., Int. Ed. Engl. 1987; 26: 338 ; Angew. Chem. 1987, 99, 354
• 14 Tabushi I, Yoshida Z, Imishiro F. Tetrahedron 1975; 31: 1833
• 15 Imashiro F, Yoshida Z, Tabushi I. Bull. Chem. Soc. Jpn. 1976; 49: 529
• 16 Heirtzler F, Hopf H, Lehne V. Liebigs Ann. 1995; 1521
• 17 Shapiro RH. Org. React. 1976; 23: 405
• 18 Adlington RM, Barrett AG. M. Acc. Chem. Res. 1983; 16: 55
• 19 Hopf H, Mlynek C, El-Tamany S, Ernst L. J. Am. Chem. Soc. 1985; 107: 6620
• 20 Hopf H, Hucker J, Ernst L. Polish J. Chem. 2007; 81: 947
• 21 Mallory FB, Mallory CW. Org. React. 1984; 30: 1
• 22 Seyferth D, Hughes WB, Heeren JK. J. Am. Chem. Soc. 1965; 87: 2847
• 23 Lenoir D. Synthesis 1977; 553
• 24 Lenoir D, Lemmen P. Chem. Ber. 1980; 113: 3112
• 25 Psiorz M, Schmidt R. Chem. Ber. 1987; 120: 1825
• 26 Heirtzler FR, Hopf H, Jones PG, Bubenitschek P, Lehne V. J. Org. Chem. 1993; 58: 2781
• 27 Jones PG, Schomburg D, Hopf H, Lehne V. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1992; 48: 2203
• 28 Rieche A, Gross H, Höft E. Chem. Ber. 1960; 93: 88
• 29 Ernst L. Chem. Unserer Zeit 1983; 17: 21
• 30 When these experiments were performed, todays’ standard methods for observing one-bond (HSQC) and long-range (HMBC) C,H-correlations in the ‘inverse mode’ were not yet available to us.

National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Spectral Database for Organic Compounds (SDBS):
• 31a http://sdbs.db.aist.go.jp/sdbs/cgi-bin/direct_frame_disp.cgi?sdbsno=672;
• 31b http://sdbs.db.aist.go.jp/sdbs/cgi-bin/direct_frame_disp.cgi?sdbsno=2338.
• 32 ACD/SpecDB, version 8.13. Advanced Chemistry Development, Inc; Toronto: 2004. ID 7153
• 33 Ernst, L. unpublished results (1988).
• 34 Sheehan M, Cram DJ. J. Am. Chem. Soc. 1969; 91: 3544
• 35 Treibs W, Klinkhammer H. Chem. Ber. 1951; 84: 671