Synthesis of Hydrophobic Derivatives of the G∧C Base for Rosette Nanotube Self-Assembly in Apolar Media Grigory Tikhomirov, †,‡ Martins Oderinde, †,‡ Darren Makeiff, † Ali Mansouri, § Weibing Lu, †,‡ Fenton Heirtzler, †,‡ Daniel Y. Kwok, | and Hicham Fenniri* ,†,‡ National Institute for Nanotechnology, National Research Council, 11421 Saskatchewan DriVe, Edmonton, Alberta T6G 2M9, Canada, Department of Chemistry and Department of Mechanical Engineering, UniVersity of Alberta, 11421 Saskatchewan DriVe, Edmonton, Alberta T6G 2M9, Canada, and Department of Mechanical Engineering, UniVersity of Calgary, 2500 UniVersity DriVe, Calgary, Alberta T2N 1N4, Canada hicham.fenniri@ualberta.ca ReceiVed February 11, 2008 Eleven self-complementary G∧C derivatives bearing hydro- phobic moieties were synthesized and characterized. One representative derivative from this family was shown to self- assemble into rosette nanotubes in hexane and form Langmuir-Blodgett films at the air-water interface. The G∧C motif, a self-cDNA base analogue featuring the hydrogen-bonding arrays of both guanine and cytosine has been shown to self-assemble into rosette nanotubes (RNTs). 1 The first step of this process is the formation of a six-membered supermacrocycle (rosette) maintained by 18 hydrogen bonds, which then stack to form a tubular structure with an inner diameter of 1.1 nm. 1,2 The RNTs are a promising class of materials due to their synthetic accessibility and amenability to chemical functionalization. For instance, RNTs with different surface groups displaying chiroptical 1a and hierarchical 1b tun- ability, high thermal stability, 1b and entropically driven self- assembly behavior 1c in aqueous or polar solvents have been reported. Here we report on the synthesis of 11 G∧C derivatives with hydrophobic substituents. These candidates were targeted to explore potential applications of RNTs as discotic liquid crystals, 3 channels, 4 nanowires, 5 and LB films 6 in nonacqueous (polar and apolar) solvents. We have also shown that a representative G∧C derivative (1f) from this family undergoes self-assembly in hexane to form RNTs and Langmuir-Blodgett films at the air-water interface. Our initial attempt at functionalizing the G∧C motif consisted in coupling alkene 10 to commercially available aryl halides using the Heck reaction. 7 Unfortunately, this reaction did not proceed. Cross-metathesis attempts between alkene 10 and p-bromostyrene using Grubbs’ second-generation catalyst 8 were equally unsuccessful. Our next strategy consisted of reductively coupling G∧C aldehyde 11 with Percec’s dendrons 9 (13-16, Scheme 1). Unfortunately, preliminary stability tests even under mild acidic conditions required for the final deprotection step led to their decomposition at the benzylic positions. To eliminate this problem we synthesized arylamine derivative 12a from amine 17 and aldehyde 11 and successfully deprotected it to form compound 1a. This approach was then applied to the synthesis of compounds 1b-e to afford the corresponding bis- trifluoroacetate or bishydrochloride salts. The second successful † National Institute for Nanotechnology. ‡ Department of Chemistry, University of Alberta. § Department of Mechanical Engineering, University of Alberta. | Department of Mechanical Engineering, University of Calgary. (1) (a) Fenniri, H.; Deng, B. L.; Ribbe, A. E. J. Am. Chem. Soc. 2002, 124, 11064–11072. (b) Moralez, J. G.; Raez, J.; Yamazaki, T.; Motkuri, R. K.; Kovalenko, A.; Fenniri, H. J. Am. Chem. Soc. 2005, 127, 8307–8309. (c) Fenniri, H.; Deng, B. L.; Ribbe, A. E.; Hallenga, K.; Jacob, J.; Thiyagarajan, P. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 6487–6492. (d) Raez, J.; Moralez, J. G.; Fenniri, H. J. Am. Chem. Soc. 2004, 126, 16298–16299. (e) Fenniri, H.; Mathivanan, P.; Vidale, K. L.; Sherman, D. M.; Hallenga, K.; Wood, K. V.; Stowell, J. G. J. Am. Chem. Soc. 2001, 123, 3854–3855. (2) (a) Mascal, M.; Hext, N. M.; Warmuth, R.; Moore, M. H.; Turkenburg, J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 2204–2206. (b) Marsh, A.; Silvestri, M.; Lehn, J.-M. Chem. Commun. 1996, 1527–1528. (c) Whitesides, G. M.; Simanek, E. E.; Mathias, J. P.; Seto, C. T.; Chin, D. N.; Mammen, M.; Gordon, D. M. Acc. Chem. Res. 1995, 28, 37–44. (d) Kolotuchin, S. V.; Zimmerman, S. C. J. Am. Chem. Soc. 1998, 120, 9092–9094. (e) Mele ´ndez, R. E.; Hamilton, A. D. Top. Curr. Chem. 1998, 198, 97–129. (f) Prins, L. J.; Reinhoudt, D. N.; Timmerman, P. Angew. Chem., Int. Ed. 2001, 40, 2382–2426. (g) Stoddart, J. F.; Tseng, H.-R. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4797–4800. (h) Lehn, J.- M. NATO ASI Ser. E: Appl. Sci. 1996, 320, 511–524. (i) MacGillivray, L. R.; Atwood, J. L. Angew. Chem., Int. Ed. 1999, 38, 1018–1033. (j) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek, J., Jr. Angew. Chem., Int. Ed. 2002, 41, 1488–1508. (k) Leininger, S.; Olenyuk, B.; Stang, P. J. Chem. ReV. 2000, 100, 853–908. (l) Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M.; Sommerdijk, N. A. J. M. Chem. ReV. 2001, 101, 4039–4070. (m) Reinhoudt, D. N.; Crego-Calama, M. Science 2002, 295, 2403–2407. (n) Mascal, M. Contemp. Org. Synth. 1994, 1, 31–46. (o) Mu ¨ller, A.; Reuter, H.; Dillinger, S. Angew. Chem., Int. Ed. Engl. 1995, 34, 2328–2361. (p) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem. ReV. 2001, 101, 3893–4011. (q) Lawrence, D. S.; Jiang, T.; Levett, M. Chem. ReV. 1995, 95, 2229–2260. (r) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem. ReV. 2001, 101, 4071–4097. (s) Ducharme, Y.; Wuest, J. D. J. Org. Chem. 1988, 53, 5787–5789. (t) Persico, F.; Wuest, J. D. J. Org. Chem. 1993, 58, 95–99. (u) Boucher, E.; Simard, M.; Wuest, J. D. J. Org. Chem. 1995, 60, 1408–1412. (3) (a) Kastler, M.; Pisula, W.; Wasserfallen, D.; Pakula, T.; Mu ¨llen, K. J. Am. Chem. Soc. 2005, 127, 4286–4296. (b) Fleming, A. J.; Coleman, J. N.; Dalton, A. B.; Fechtenko ¨ tter, A.; Watson, M. D.; Mu ¨ llen, K.; Byrne, H. J.; Blau, W. J. J. Phys. Chem. B 2003, 107, 37–43. (4) Bong, D. T.; Clark, T. D.; Granja, J. R.; Ghadiri, M. R. Angew. Chem., Int. Ed. 2001, 40, 988–1011. (5) Hill, J. P.; Jin, W.; Kosaka, A.; Fukushima, T.; Ichihara, H.; Shimomura, T.; Ito, K.; Hashizume, T.; Ishii, N.; Aida, T. Science 2004, 304, 1481–1483. (6) Yang, P.; Kim, F. ChemPhysChem 2002, 3, 503–506. (7) Jeffery, T. Tetrahedron Lett. 1985, 26, 2667–2670. (8) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953– 956. (9) Johansson, G.; Percec, V.; Ungar, G.; Abramic, D. J. Chem. Soc., Perkin Trans. 1 1994, 447–459. 10.1021/jo800344b CCC: $40.75  2008 American Chemical Society 4248 J. Org. Chem. 2008, 73, 4248–4251 Published on Web 05/01/2008