ORGANIC LETTERS
Synthesis of [2]Rotaxanes by the Copper-Mediated Threading Reactions of Aryl Iodides with Alkynes
XXXX Vol. XX, No. XX 000–000
Kenta Ugajin,† Eiko Takahashi,† Ryu Yamasaki,† Yuichiro Mutoh,† Takeshi Kasama,‡ and Shinichi Saito*,† Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku, Tokyo, 162-8601, Japan, and Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
[email protected] Received April 10, 2013
ABSTRACT
The catalytic activity of the macrocyclic phenanthrolinecopper(I) complex is utilized for the Sonogashira-type reaction to synthesize [2]rotaxanes. Thus, [2]rotaxanes were prepared by reactions between terminal alkynes and aryl iodides in the presence of the macrocyclic copper complex. Bulky substituents were introduced to the substrates to stabilize the rotaxane. The bond-forming reaction proceeded selectively inside the macrocyclic complex so that the rotaxanes could be synthesized.
Rotaxane is a well-known example of mechanically interlocked compounds, which consists of a cyclic component and a linear component with bulky substituents located at both ends. With sufficiently large substituents, rotaxanes would exist as a stable molecule and two components would not dissociate easily. Various approaches have been reported for the synthesis of rotaxanes, and the template method has been widely used.1 Recently, a new approach has been reported for the synthesis of interlocked compounds such as rotaxanes2 †
Tokyo University of Science. Tokyo Medical and Dental University. (1) Reviews: (a) Schill, G. Catenanes, Rotaxanes, and Knots; Academic Press: New York, 1971. (b) Molecular Catenanes, Rotaxanes and Knots; Dietrich-Buchecker, C. O., Sauvage, J. P., Eds.; Wiley-VCH: New York, 1999. (c) Sauvage, J. P. Acc. Chem. Res. 1990, 23, 319–327. (d) Hoss, R.; V€ ogtle, F. Angew. Chem., Int. Ed. Engl. 1994, 33, 375–384. (e) Amabilino, D. B.; Stoddart, J. F. Chem. Rev. 1995, 95, 2725–2828. (f) J€ ager, R.; V€ ogtle, F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930–944. (g) Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev. 1998, 98, 1959–1976. (h) Sauvage, J. P. Acc. Chem. Res. 1998, 31, 611–619. (i) Raymo, F. M.; Stoddart, J. F. Chem. Rev. 1999, 99, 1643–1663. (j) Tian, H.; Wang, Q.C. Chem. Soc. Rev. 2006, 35, 361–374. (k) Crowley, J. D.; Goldup, S. M.; Lee, A.-L.; Leigh, D. A.; McBurney, R. T. Chem. Soc. Rev. 2009, 38, 1530–1541. (l) Beves, J. E.; Blight, B. A.; Campbell, C. J.; Leigh, D. A.; McBurney, R. T. Angew. Chem., Int. Ed. 2011, 50, 9260–9327. ‡
and catenanes.3 Thus, the catalytic activity of the macrocyclic metal complex has been utilized for the efficient synthesis of interlocked compounds. Since the bond formation reaction proceeded selectively inside the macrocyclic ring, the interlocked compounds were isolated in good to high yields. This approach has been recently applied to the synthesis of highly functionalized molecules.4 (2) (a) Leigh, D. A.; Aucagne, V.; H€anni, K. D.; Lusby, P. J.; Walker, D. B. J. Am. Chem. Soc. 2006, 128, 2186–2187. (b) Saito, S.; Takahashi, E.; Nakazono, K. Org. Lett. 2006, 8, 5133–5136. (c) Berna, J.; Crowley, J. D.; Goldup, S. M.; H€anni, K. D.; Lee, A.-L.; Leigh, D. A. Angew. Chem., Int. Ed. 2007, 46, 5709–5713. (d) Crowley, J. D.; H€anni, K. D.; Lee, A.-L.; Leigh, D. A. J. Am. Chem. Soc. 2007, 129, 12092–12093. (e) Goldup, S. M.; Leigh, D. A.; Lusby, P. J.; McBurney, R. T.; Slawin, A. M. Z. Angew. Chem., Int. Ed. 2008, 47, 3381–3384. (f) Berna, J.; Goldup, S. M.; Lee, A.-L.; Leigh, D. A.; Symes, M. D.; Teobaldi, G.; Zerbetto, F. Angew. Chem., Int. Ed. 2008, 47, 4392–4396. (g) Crowley, J. D.; H€anni, K. D.; Leigh, D. A.; Slawin, A. M. Z. J. Am. Chem. Soc. 2010, 132, 5309–5314. (h) Crowley, J. D.; Goldup, S. M.; Gowans, N. D.; Leigh, Ronaldson, V. E.; Slawin, A. M. Z. J. Am. Chem. Soc. 2010, 132, 6243–6248. (i) Goldup, S. M.; Leigh, D. A.; McBurney, R. T.; McGonigal, P. R.; Plant, A. Chem. Sci. 2010, 1, 383–386. (j) Cheng, H. M.; Leigh, D. A.; Maffei, F.; McGonigal, P. R.; Slawin, A. M. Z.; Wu, J. J. Am. Chem. Soc. 2011, 133, 12298–12303. (k) Saito, S.; Takahashi, E.; Wakatsuki, K.; Inoue, K.; Orikasa, T.; Sakai, K.; Yamasaki, R.; Mutoh, Y.; Kasama, T. J. Org. Chem. 2013, 78, 3553–3560. 10.1021/ol400992p
r XXXX American Chemical Society
Table 1. Reaction of the Alkyne with Aryl Iodides in the Presence of Macrocyclic PhenanthrolineCopper(I) Catalyst (1)
We were interested in the catalytic activity of macrocyclic phenanthrolinecopper(I) complexes and reported the synthesis of rotaxanes by the copper-mediated oxidative homocoupling reaction of alkynes.2b,k The study indicated that the copper complexes could be used as the catalysts for other coupling reactions, and rotaxanes with (3) (a) Sato, Y.; Yamasaki, R.; Saito, S. Angew. Chem., Int. Ed. 2009, 48, 504–507. (b) Goldup, S. M.; Leigh, D. A.; Long, T.; McGonigal, P. R.; Symes, M. D.; Wu, J. J. Am. Chem. Soc. 2009, 131, 15924–15929. (4) (a) Lahlali, H.; Jobe, K.; Watkinson, M.; Goldup, S. M. Angew. Chem., Int. Ed. 2011, 50, 4151–4155. (b) Langton, M. J.; Matichak, J. D.; Thompson, A. L.; Anderson, H. L. Chem. Sci. 2011, 2, 1897–1901. (c) Barran, P. E.; Cole, H. L.; Goldup, S. M.; Leigh, D. A.; McGonigal, P. R.; Symes, M. D.; Wu, J.; Zengerle, M. Angew. Chem., Int. Ed. 2011, 50, 12280–12284. (d) Weisbach, N.; Baranova, Z.; Gauthier, S.; Reibenspies, J. H.; Gladysz, J. A. Chem. Commun. 2012, 48, 7562– 7564. (e) Movsisyan, L. D.; Kondratuk, D. V.; Franz, M.; Thompson, A. L.; Tykwinski, R. R.; Anderson, H. L. Org. Lett. 2012, 14, 3424–3426. (f) Lewandowski, B.; De Bo, G.; Ward, J. W.; Papmeyer, M.; Kuschel, S.; Aldegunde, M. J.; Gramlich, P. M. E.; Heckmann, D.; Goldup, S. M.; D’Souza, D. M.; Fernandes, A. E.; Leigh, D. A. Science 2013, 339, 189–193. (5) For examples of the Cu-catalyzed Sonogashira-type reactions, see: (a) Bates, C. G.; Saejueng, P.; Venkataraman, D. Org. Lett. 2004, 6, 1441–1444. (b) Monnier, F.; Turtaut, F.; Duroure, L.; Taillefer, M. Org. Lett. 2008, 10, 3203–3206. B
Figure 1. 1H NMR spectra of 9a, 10a, and 12 (500 MHz, CDCl3).
various axle components could be prepared. In this paper we report the synthesis of [2]rotaxane by a Sonogashiratype cross-coupling reaction5 mediated by a macrocyclic phenanthrolinecopper(I) complex. We examined the catalytic activity of a macrocyclic phenanthrolinecopper(I) complex 12b for the cross-coupling reactions between 4-(octyloxy)phenylacetylene 2 and iodobenzoates 3, and the results are summarized in Table 1. The reaction between 2 and methyl 2-iodobenzoate 3a proceeded in the presence of 1 and K2CO3, and the product was isolated Org. Lett., Vol. XX, No. XX, XXXX
Table 2. Synthesis of [2]Rotaxanes by the Sonogashira-Type Cross-Coupling Reaction
entry
aryl iodide
time (h)
1 2 3
7a 7b 7c
24 54 33
a
producta (yield) 9a (52%)b 9b (24%)b 9c (24%)b
10a (44%)c 10b (37%)c 10c (33%)c
11 (7%)b 11 (16%)b 11 (14%)b
Compounds 9a,n10a are ortho-isomers; 9b, 10b are meta-isomers; and 9c, 10c are para-isomers. b The yields were based on 1. c The yields were based on 8.
Scheme 1. Synthesis of Iodobenzoates with a Bulky Substituent
in good yield (entry 1). When ethyl 3-iodobenzoate 3b was used, the yield of the product decreased (entry 2). Though the Org. Lett., Vol. XX, No. XX, XXXX
reaction of 2 with the para-isomer 3c proceeded, the yield of the product was disappointing (entry 3). These results imply that the coordination of the carbonyl group to the Cu atom of the aryl copper species, which would be formed by the reaction of aryl iodide with the copper complex, would play an important role (vide infra). To apply this reaction for the synthesis of rotaxanes, substrates with bulky substituents were required. We chose the tris(40 -ethylbiphenyl)methyl group as the bulky substituent and introduced this substituent to iodobenzoates. The synthesis of the precursors 7ac was carried out by the condensation of the iodobenzoic acid with an alcohol 62k under standard conditions (Scheme 1). The reactions proceeded smoothly, providing the corresponding esters in good to high yields. The synthesis of [2]rotaxanes was studied by the reaction of 1, 7ac, and 8.2b The results are summarized in Table 2. A mixture of 1 (1.0 equiv), 7 (2.2 equiv), 8 (2.0 equiv), and K2CO3 (4.0 equiv) was heated at 120 °C under Ar. C
The mixture was cooled to rt and treated with aqueous ammonia6 to remove the copper ion. When the ortho-isomer (7a) was used as the substrate, [2]rotaxane 9a was isolated in 52% yield (based on 1). The cross-coupling product 10a and [2]rotaxane 11,2k which was formed by the oxidative dimerization of alkyne 8, were also isolated (entry 1). When 3-iodobenzoate 7b was used, [2]rotaxane 9b was obtained in 24% yield (entry 2). The reaction of 4-iodobenzoate 7c also gave the [2]rotaxane 9c in 24% yield (entry 3). It is noteworthy that the yields of 9ac do not correlate well with the yields of the model reactions reported in Table 1: the yield of 9a was better, as expected, though the yields of 9b,c were higher than we anticipated by the results shown in Table 1.7 The structures of the rotaxanes were elucidated by spectroscopic methods. The 1H NMR spectra of 9a, 10a, and 128 are shown in Figure 1. In the NMR spectrum of 9a, the upfield shifts of the protons of the phenanthroline moiety (Ha He) were observed. The methylene protons adjacent to the oxygen atom (H3, H4, Hf, Hg) also shifted to higher fields. These shifts are frequently observed for other rotaxanes we synthesized in previous studies. The splitting of the protons of the resorcinol moiety (Hh, Hi) of 9a is another strong indicator for the formation of the rotaxane. The structures of the rotaxanes were further confirmed by mass spectroscopy (see Supporting Information). A plausible mechanism5 of the cross-coupling reaction is described in Scheme 2. In the presence of a base, the reaction of Cu(I) complex with the alkyne would proceed to yield a Cu(I) acetylide intermediate. Next, a Cu(III) complex was generated by the oxidative addition of aryl iodide to the acetylide. This process might be accelarated by the presence of a carbonyl group located at the ortho position (i.e., in the (6) Jackson, D.; Megiatto, Jr.; Schuster, D. I. Org. Lett. 2011, 13, 1808–1811. (7) Trace amounts of the starting materials were also recovered. The 1,3-diyne product, which would be formed by the oxidative dimerization of 8, was not isolated probably because the amount of the product was very small. (8) Saito, S.; Nakazono, K.; Takahashi, E. J. Org. Chem. 2006, 71, 7477–7480.
D
Scheme 2. A Plausible Mechanism of the Cross-Coupling Reaction
reaction of 7a) since the coordination of the carbonyl group to the copper atom would stabilize the Cu(III) complex. Finally, the formation of a new CC bond would proceed by reductive elimination. When this process proceeded inside the ring, the rotaxane would be isolated as the final product. In summary, we succeeded in the synthesis of [2]rotaxanes by the Sonogashira-type cross-coupling reaction between a terminal alkyne and aryl iodides. The macrocyclic phenanthrolinecopper(I) complex 1 was observed to be suitable for this transformation, and a series of isomeric rotaxanes were prepared. The study provided a new and unique method for the synthesis of rotaxanes. Acknowledgment. We thank the UBE foundation for financial support. Supporting Information Available. Detailed experimental procedures and spectral data for 410. This material is available free of charge via the Internet at http://pubs.acs.org. The authors declare no competing financial interest.
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