Palladium-Catalyzed 4-Fold Domino Reaction for the Synthesis of a Polymeric Double Switch

Article abstract of DOI:10.1021/acs.orglett.8b00553

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 subs

Full text of DOI:10.1021/acs.orglett.8b00553

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Palladium-Catalyzed 4‑Fold Domino Reaction for the Synthesis of a
Polymeric Double Switch
Taukeer A. Khan,† Torsten Fornefeld,‡ Dennis Hubner,‡ Philipp Vana,‡ and Lutz F. Tietze*,†
̈
†Institute of Organic and Biomolecular Chemistry, Georg-August-University of Gottingen, Tammannstr. 2, D-37077 Gottingen,
̈
̈
Germany
‡Institute of Physical Chemistry, Georg-August-University of Gottingen, Tammannstr. 6, D-37077 Gottingen, 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.
ver the past years, molecular photoswitches1 have
controlled changes of their stereochemistry in the range of
picoseconds.9
Oreceived much attention, because of their promising
role as active control elements in functional materials;2−4
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
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, bio-
medicine, 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 organiza-
tion, 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 pH-
and 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-
Received: February 14, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00553
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Letter
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 2,6-
Scheme 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 dichloro-
methane (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 polymer-
ization 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
B
DOI: 10.1021/acs.orglett.8b00553
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molar fraction of BA in the polymer was obtained as FBA = 0.86,
the molar fraction in the feed was fBA = 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.
Scheme 3. RAFT Copolymerization of n-Butyl Acrylate and
Compound 1 with 2-Cyano-2-propyl Dodecyl
Trithiocarbonate as a Chain Transfer Agent
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b00553.
Complete experimental details and characterization data
for the synthesized compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ltietze@gwdg.de.
ORCID
Lutz F. Tietze: 0000-0003-3847-0756
Notes
The authors declare no competing financial interest.
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 Gottingen
̈
for a postdoctoral fellowship.
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Table 1. Properties of 13 [P(BA-co-1)] Synthesized by RAFT
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parameter
polymer
value
13 [P(BA-co-1)]
[BA]:[1]:[CPDT]
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14
M (kg mol−1
)
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Đ
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FBA
FC1
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