Letter Cite This: Org. Lett. 2018, 20, 2007−2010
pubs.acs.org/OrgLett
Palladium-Catalyzed 4‑Fold Domino Reaction for the Synthesis of a Polymeric Double Switch Taukeer A. Khan,† Torsten Fornefeld,‡ Dennis Hübner,‡ Philipp Vana,‡ and Lutz F. Tietze*,† †
Institute of Organic and Biomolecular Chemistry, Georg-August-University of Göttingen, Tammannstr. 2, D-37077 Göttingen, Germany ‡ Institute of Physical Chemistry, Georg-August-University of Göttingen, Tammannstr. 6, D-37077 Göttingen, Germany S Supporting Information *
ABSTRACT: A palladium-catalyzed 4-fold domino reaction consisting of two carbopalladation reactions and two C−H activation reactions, followed by the introduction of an acrylate moiety, led to the tetra-substituted helical alkene A2, using the dialkyne A3 as a substrate. The alkene was copolymerized with butyl acrylate by using the reversible addition−fragmentation chain transfer polymerization (RAFT) to give the desired polymeric switch A1.
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ver the past years, molecular photoswitches1 have received much attention, because of their promising role as active control elements in functional materials;2−4 moreover, they hold great promise as molecular electronic and photonic devices. The unique characteristic of a photoswitch lies in its reversibility and the ability to store information on a molecular level. Their application in nanotechnology, biomedicine, and computer chip design opens up entirely new horizons. The switches can be incorporated into polymers or in supramolecular assemblies to modulate properties such as surface wettability,5a polymer elasticity,5b lateral pressure profile of bilayers, host−guest recognition, supramolecular organization, catalysis,5c color, fluorescence, conductance and enzyme activity.5d Another possible function of these polymers is the ability to form different predetermined temporary shapes with subsequent recovery of their original shape via remote light activation.6,7 However, the field of light-responsive polymeric materials has advanced much more slowly than the area of pHand temperature-sensitive polymers. As a general new class of molecular switches and machines, helical alkenes have been developed by Feringa.8 In this direction, our group has recently reported on the design of novel tetrasubstituted alkenes with intrinsic helical chirality. Photophysical investigations of some of these compounds showed pronounced switching properties through light© 2018 American Chemical Society
controlled changes of their stereochemistry in the range of picoseconds.9 Herein, we describe a facile and efficient synthesis of a polymeric tetra-substituted overcrowded alkene with two switching moieties that might be useable in developing advanced materials and novel organic electronic devices. For the polymerization, the monomeric acrylate 1 was used to allow the embedment of the two helical double bonds into a polymeric matrix and thus permit the transfer of the switching state onto the macroscopic system.6,10,11 The synthesis of 1 was accomplished by using a palladium-catalyzed 4-fold domino reaction consisting of two carbopalladation reactions and two C−H activation reactions.12−14 (See Figure 1.) Domino reactions of this type have recently also been used by us in the synthesis of fluorescent dyes.15 It should be noted that domino reactions for the synthesis of overcrowded alkenes were also described by Lautens et al.16 and Zhu et al.17 As one of the starting materials, the iodoaryl ether 2 was employed, being accessible through a nucleophilic aromatic substitution of chloronitrobenzene with 4-methoxyphenol followed by reduction of the nitro group and a Sandmeyer reaction, according to a known procedure.9 Received: February 14, 2018 Published: March 20, 2018 2007
DOI: 10.1021/acs.orglett.8b00553 Org. Lett. 2018, 20, 2007−2010
Letter
Organic Letters
Scheme 2. Sonogashira Reaction of 2 and 9 To Give 10, as Well As Domino Reaction of 11 To Give 12 after Deprotection with Final iIntroduction of the Acrylate Moiety with Formation of 1
Figure 1. Structure of 1.
For the synthesis of the dialkyne 9 (Scheme 1) as the second partner of the Sonogashira reaction, commercially available 2,6Scheme 1. Synthesis of 9
introduction of the acryl moiety at the free aromatic hydroxyl group, 12 was treated with acryloyl chloride and triethylamine in CH2Cl2 to give 1 with very good yield (Scheme 2). For the incorporation of the two chiral alkene moieties in a polymeric matrix, we used a copolymerization of 1 and n-butyl acrylate by reversible-deactivation radical polymerization employing the reversible addition−fragmentation chain transfer (RAFT) mechanism (see Scheme 3). RAFT polymerization provides polymers with low dispersities and allows one to tailor the molar mass.19a In addition, the resulting polymer carries a RAFT end group, enabling further synthetic steps to form, for example, a block copolymer. 2-Cyano-2-propyl dodecyl trithiocarbonate (CPDT) was used as a chain transfer agent, because of its excellent control over the polymerization of acrylates.19a,b For the polymerization, the solvent was crucial. Toluene was not suitable, since compound 1 was not incorporated, probably because of the low solubility of 1 in this solvent. With 1,2-dimethoxyethane better results could be obtained, but the molecular weight of the obtained polymer was rather low. The best solvent was DMF. The polymer 13 [P(BA-co-1)] was analyzed by size exclusion chromatography (SEC) and proton nuclear magnetic resonance spectroscopy (1H NMR, Figure 2) in deuterated dichloromethane (DCM). The results of the characterization are summarized in Table 1. The size exclusion chromatogram of 13 P(BA-co-1) shows a monomodal molecular weight distribution, indicating the formation of a polymer. The relatively high dispersity (Đ = 1.7) is characteristic for the RAFT polymerization of sterically demanding monomers and consistent with
dimethylanisole was nitrated, followed by zinc reduction, to provide amine 3, using known methods,18 which we have slightly modified. The sensitive aniline 3 was converted immediately to the dibromo derivative 4 by treatment with bromine in CH2Cl2 in 95% yield. The deamination of 4 under standard reaction conditions afforded compound 5 in 84% yield, which could be utilized to carry out further steps in the synthesis of 1. However, this approach is not very attractive, because of problems with the necessary cleavage of the methyl ether on a later stage. Therefore, we cleaved the methyl ether moiety in 5 using BBr3, which is very simple to give 6 with 99% yield. The phenolic hydroxyl group in 6 was then protected as MOM ether 7. Subsequent bromination of the methyl group with NBS and AIBN gave the tetra-bromo compound 8 in 84% yield, which was converted to dialkyne 9 through substitution reaction with propargyl alcohol. To allow a better optimization of the following steps, we first performed a separate Sonogashira reaction of 2 and 9 to give compound 10 in 76% yield (see Scheme 2). Compound 10 was then treated with TMSBr to get the unprotected compound 11. For the following domino reactions of 11 consisting of two carbopalladation reactions and two C−H activation reactions, we used Pd(OAc)2 and PPh3 and (nBu)4NOAc as base in DMF under microwave irradiation, which proceeded in just 35 min to furnish the desired domino product 12 in 56% yield. For the 2008
DOI: 10.1021/acs.orglett.8b00553 Org. Lett. 2018, 20, 2007−2010
Letter
Organic Letters Scheme 3. RAFT Copolymerization of n-Butyl Acrylate and Compound 1 with 2-Cyano-2-propyl Dodecyl Trithiocarbonate as a Chain Transfer Agent
molar fraction of BA in the polymer was obtained as FBA = 0.86, the molar fraction in the feed was f BA = 0.95. Hence, the incorporation of 1 into the polymer is favored. The authors propose the higher stability of a 1-centered radical, because of the higher sterical demand of the side group as an explanation. In conclusion, we have developed a facile and efficient synthesis of a novel polymer 13 [P(BA-co-1)] containing a heterocycle with two helical tetrasubstituted alkenes using RAFT copolymerization of compound 1 and n-butyl acrylate. For the synthesis of 1, a 4-fold domino process with a C−H activation reaction as the final step was employed. Our next goal will be the synthesis of polymeric double switches, where the two switching moieties are part of a polymeric chain.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00553. Complete experimental details and characterization data for the synthesized compounds (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Lutz F. Tietze: 0000-0003-3847-0756 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank the Deutsche Forschungsgemeinschaft (DFG), the State of Lower Saxony, the VW-foundation for their generous support. T.K. thanks the Georg-August-University Göttingen for a postdoctoral fellowship.
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(1) Representative recent overviews are given in: (a) Molecular Switches, 2nd Edition; Feringa, B. L., Browne, W. R., Eds.; Wiley− VCH: Weinheim, Germany, 2011. (b) New Frontiers in Photochromism; Irie, M., Yokoyama, Y., Seki, T., Eds.; Springer: Tokyo, Japan, 2013. (c) Fredrich, S.; Göstl, R.; Herder, M.; Grubert, L.; Hecht, S. Angew. Chem., Int. Ed. 2016, 55, 1208−1212. (2) (a) Abendroth, J. M.; Bushuyev, O. S.; Weiss, P. S.; Barrett, C. J. ACS Nano 2015, 9, 7746−7768. (b) Orgiu, E.; Samori, P. Adv. Mater. 2014, 26, 1827−1845. (c) Russew, M.-M.; Hecht, S. Adv. Mater. 2010, 22, 3348−3360. (3) Bisoyi, H. K.; Li, Q. Angew. Chem., Int. Ed. 2016, 55, 2994−3010. (4) (a) Tietze, L. F.; Hungerland, T.; Eichhorst, C.; Dufert, A.; Maaß, C.; Stalke, D. Angew. Chem., Int. Ed. 2013, 52, 3668−3671. (b) Feringa, B. L.; Wynberg, H. J. Am. Chem. Soc. 1977, 99, 602−603. (c) Ruangsupapichat, N.; Pollard, M. M.; Harutyunyan, S. R.; Feringa, B. L. Nat. Chem. 2011, 3, 53−60. (d) Qu, B. L.; Feringa, D.-H. Angew. Chem., Int. Ed. 2010, 49, 1107−1110. (5) (a) Ge, H.; Wang, G.; He, Y.; Wang, X.; Song, Y.; Jiang, L.; Zhu, D. ChemPhysChem 2006, 7, 575−578. (b) Hugel, T.; Holland, N. B.; Cattani, A.; Moroder, L.; Seitz, M.; Gaub, H. E. Science 2002, 296, 1103−1106. (c) de Jong, J. J. D.; Lucas, L. N.; Kellogg, R. M.; van Esch, J. H.; Feringa, B. L. Science 2004, 304, 278−281. (d) Browne, W. R.; Feringa, B. L. Nat. Nanotechnol. 2006, 1, 25−35. (6) Lendlein, A.; Jiang, H.; Jünger, O.; Langer, R. Nature 2005, 434, 879−882.
Figure 2. 1H NMR Spectra of 13 [P(BA-co-1)] in DCM. Signals marked in blue originate from compound 1; signals marked in green originate from butyl acrylate.
Table 1. Properties of 13 [P(BA-co-1)] Synthesized by RAFT Copolymerization parameter
value
polymer [BA]:[1]:[CPDT] M̅ n (kg mol−1) Đ FBA FC1
13 [P(BA-co-1)] 300:15:1 14 1.70 0.86 0.14
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DOI: 10.1021/acs.orglett.8b00553 Org. Lett. 2018, 20, 2007−2010
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DOI: 10.1021/acs.orglett.8b00553 Org. Lett. 2018, 20, 2007−2010
