Convergent Synthesis of 1,1′-Biisoquinolines Tethered to Calamitic Subunits

Abstract

A convergent synthesis of a series of 4,4′-functionalized 1,1′-biisoquinolines via 1-chloro-4-hydroxyisoquinoline and substituted biphenyl- and phenylpyrimidine ethers as building blocks is described. The latter were prepared by Williamson etherification of the respective 4-hydroxybiphenyl and -phenylpyrimidine precursors with dibromoalkanes, allowing variation of the spacer lengths. 1-Chloro-4-hydroxyisoquinoline was obtained from N-phthalimidoglycine ethyl ester through a Gabriel-Colman reaction as a key step. Linkage of the building blocks by etherification in the presence of potassium carbonate gave the isoquinolines, which were submitted to a nickel(II) chloride mediated homocoupling to yield the ligand systems.

Key words

biisoquinolines - biphenyls - ligands - homocoupling - Williamson etherification

References

• For reviews, see:
• 1a Laschat S. Baro A. Steinke N. Giesselmann F. Hägele C. Scalia G. Judele R. Kapatsina E. Sauer S. Schreivogel A. Tosoni M. Angew. Chem. Int. Ed.  2007,  46:  4832 ; Angew. Chem. 2007, 119, 4916
• 1b Piguet C. Bünzli J.-CG. Donnio B. Guillon D. Chem. Commun.  2006,  3755 
• 1c Donnio B. Guillon D. Deschenaux R. Bruce DW. In Comprehensive Coordination Chemistry II   Vol. 7:  McCleverty JA. Meyer TJ. Elsevier; Oxford: 2004.  p.357-627  
• 1d Serrano JL. Sierra T. Coord. Chem. Rev.  2003,  242:  73 
• 1e Binnemans K. Görller-Walrand C. Chem. Rev.  2002,  102:  2303 
• 1f Collinson SR. Martin F. Binnemans K. Van Deun R. Bruce DW. Mol. Cryst. Liq. Cryst.  2001,  364:  745 
• 1g Hoshino N. Coord. Chem. Rev.  1998,  174:  77 
• 1h Giroud-Godquin AM. In Handbook of Liquid Crystals   Vol. 2B:  Demus D. Goodby J. Gray GW. Spiess H.-W. Vill V. Wiley-VCH; Weinheim: 1998.  p.901 
• 1i Barbera J. In Metallomesogens   Serrano JL. VCH; Weinheim: 1996.  p.131 
• 1j Hudson SA. Maitlis PM. Chem. Rev.  1993,  93:  861 
• 1k Espinet P. Esteruelas MA. Oro LA. Serrano JL. Sola E. Coord. Chem. Rev.  1992,  117:  215 
• 1l Giroud-Godquin A.-M. Maitlis PM. Angew. Chem. Int. Ed. Engl.  1991,  30:  375 ; Angew. Chem. 1991, 103, 370
• 2 For an excellent review on atropselective synthesis of biaryl and heterobiaryl compounds, see: Bringmann G. Price Mortimer AJ. Keller PA. Gresser MJ. Garner J. Breuning M. Angew. Chem. Int. Ed.  2005,  44:  5384 ; Angew. Chem. 2005, 117, 5518
• For reviews, see:
• 3a Goodby JW. In Handbook of Liquid Crystals   Vol. 2A:  Demus D. Goodby J. Gray GW. Spiess H.-W. Vill V. Wiley-VCH; Weinheim: 1998.  p.3 
• 3b Goodby JW. In Handbook of Liquid Crystals   Vol. 2A:  Demus D. Goodby J. Gray GW. Spiess H.-W. Vill V. Wiley-VCH; Weinheim: 1998.  p.411 
• 3c Guillon D. In Handbook of Liquid Crystals   Vol. 2A:  Demus D. Goodby J. Gray GW. Spiess H.-W. Vill V. Wiley-VCH; Weinheim: 1998.  p.23 
• 3d Toyne KJ. In Handbook of Liquid Crystals   Vol. 2A:  Demus D. Goodby J. Gray GW. Spiess H.-W. Vill V. Wiley-VCH; Weinheim: 1998.  p.47 
• 4a Organikum   21st ed.:  Wiley-VCH; Weinheim: 2001.  p.380 
• 4b Buu-Hoï NP. Xuong ND. van Thang K. Recl. Trav. Chim. Pays-Bas  1953,  72:  774 
• 5 Gray GW. Mosley A. Mol. Cryst. Liq. Cryst.  1978,  48:  233 
• 6 Westland RD. Holmes JL. Mouk ML. Marsh DD. Cooley RA. Dice JR. J. Med. Chem.  1968,  11:  1190 
• 7 Liepa AJ. Aust. J. Chem.  1981,  34:  2647 
• 8 Lloyd D. Reichardt C. Struthers M. Liebigs Ann. Chem.  1986,  1368 
• 9 Dox AW. Org. Synth.  1941,  1:  5 
• 10 Hooley RJ. Rebek J. Org. Lett.  2007,  9:  1179 
• 11 Sugita S.-I. Toda S. Yashiyasu T. Teraji T. Murayama A. Mol. Cryst. Liq. Cryst.  1994,  239:  113 
• 12 Sugita S.-I. Takeno H. Teraji T. Mol. Cryst. Liq. Cryst.  1991,  206:  139 
• 13a Gabriel S. Colman J. Ber. Dtsch. Chem. Ges.  1900,  33:  980 
• 13b Nunami K. Suzuki M. Matsumoto K. Miyoshi M. Yoneda N. Chem. Pharm. Bull.  1979,  27:  1373 
• 13c Tréfouël MJ. C. R. Hebd. Seances Acad. Sci.  1965,  261:  1339 
• 14 Bolm C. Ewald M. Zehnder M. Neuburger MA. Chem. Ber.  1992,  125:  453 
• 15a Fujii M. Honda A. J. Heterocycl. Chem.  1992,  29:  931 
• 15b Iyoda M. Otsuka H. Sato K. Nisato N. Oda M. Bull. Chem. Soc. Jpn.  1990,  63:  80 

16

Application of the catalyst system NiCl₂˙6H₂O/Zn/PPh₃ to
4-ethoxy-1-bromoisoquinoline yielded only 38% of the desired 1,1′-biisoquinoline 22a, whereas no product was formed with NiBr₂(PPh₃)₂/Zn/Et₄NI. As the latter system catalyzed the reaction with 4-ethoxy-1-chloroisoquinoline, the experiments were carried out with chloroisoquinolines 20 in the presence of nickel chloride as the catalyst.