Iterative molecular assembly based on the cation-pool method. Convergent synthesis of dendritic molecules

Article abstract of DOI:10.1021/ja803487q

An iterative method for molecular assembly has been developed based on the cation-pool method using (trimethylsilyl)diphenylmethane as a building block. The silyl group works as both an activating group of the benzene ring in the Friedel-Crafts type reaction and an electroauxiliary in the subsequent low temperature anodic oxidation to generate dendritic diarylcarbenium ions, which were well characterized by low-temperature NMR spectroscopy. The convergent synthesis of dendritic molecules has been achieved by repeating the sequence. Copyright

Full text of DOI:10.1021/ja803487q

Published on Web 07/29/2008
Iterative Molecular Assembly Based on the Cation-Pool Method. Convergent
Synthesis of Dendritic Molecules
Toshiki Nokami, Kousuke Ohata, Masafumi Inoue, Hiroaki Tsuyama, Akito Shibuya, Kazuya Soga,
Masayuki Okajima, Seiji Suga, and Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity
Nishikyo-ku, Kyoto 615-8510, Japan
Received May 9, 2008; E-mail: yoshida@sbchem.kyoto-u.ac.jp
Iterative processes that are based on multiple use of the same
reaction sequence serve as powerful methods for construction of
relatively large structurally well-defined organic molecules.1 Various
iterative processes have been developed, and they are widely utilized
in the synthesis of organic compounds. To achieve such processes,
a method involving generation and accumulation of a highly reactive
Figure 1. Iterative process based on activation-coupling sequence.
species (activation) followed by the coupling reaction with a
building block, which is equipped with a potential active site for
the generation of the reactive species in the next sequence, is quite
effective (Figure 1).
Scheme 1
The cation-pool method2 that involves generation and accumula-
tion of highly reactive organic cations using anodic oxidation3 in
the absence of a nucleophile seems to be suitable for the present
purpose. Recently we have reported that diarylcarbenium ions 24
can be generated and accumulated by low-temperature anodic
oxidation of diarylmethanes 1 (Scheme 1a).5
Based on this finding, the following working hypothesis came
to mind. If diarylcarbenium ion 2 reacts with two benzene rings of
diphenylmethane derivative 3 in a Friedel-Crafts manner (Scheme
1b), the resulting extended diarylmethane 4 could be used as a
precursor of the next activation-coupling sequence (Scheme 1c).
Consequently, multiple use of this sequence leads to convergent
synthesis6 of dendritic molecules7 (Scheme 1). This concept works,
and we report herein the results of our proof-of-principle study on
iterative molecular assembly using the cation-pool method.
Although the anodic oxidation of diphenylmethane led to the
formation of a complex mixture, the reactions of substituted
diphenylmethanes 1 (Ar ) p-FC6H4, p-CH3C6H4, p-CH3OC6H4,
p-ClC6H4, etc.) gave rise to effective formation of the corresponding
diarylcarbenium ion pools.3 We chose to use di(p-fluo-
ropheny)methane 1a (Ar ) p-FC6H4) as a starting material because
the conversion to diarylcarbenium ion 2a is very efficient among
the examined (Scheme 2). The resulting 2a was allowed to react
with diphenylmethane 3a (X ) H), but the expected 1:2 adduct 4a
(Ar ) p-FC6H4, X ) H) was not produced. Instead, the 1:1 adduct
7 was obtained in very low yield (11%).
To solve this problem, a silyl-substituted diphenylmethane, 3b
(X ) SiMe3), was used because the introduction of a silyl group at
the benzylic position increases the HOMO level of the benzene
ring to increase its reactivity.8 Also if the outer-sphere electron
transfer takes place, the C-Si bond in the resulting radical cation
is readily cleaved.9 However, Mayr, Fukuzumi, and co-workers
reported that the outer-sphere electron transfer is definitely excluded
for the reaction of diarylcarbenium ions with nucleophiles.10 In
fact, the reaction of 3b (X ) SiMe3) with 2a proceeded without
cleavage of the C-Si bond to give desired 4b (Ar ) p-FC6H4, X
) SiMe3) [G-1, the first generation] in 79% yield.11
Scheme 2
sequence, the silyl group works as an electroauxiliary,12 which
activates the molecule toward oxidation and controls the reaction
pathway. In fact, the oxidation potential of 4b (1.25 V) was found
to be much less positive than those of 1a (1.77 V) and 3a (1.81
V). The anodic oxidation of 4b took place smoothly, and the C-Si
bond was cleaved selectively13 without affecting other C-H bonds
at benzylic positions. The resulting 5 (Ar ) p-FC6H4) was allowed
to react with 3b (X ) SiMe3) to give 6 (Ar ) p-FC6H4, X ) SiMe3)
[G-2, the second generation] in 75% yield.14
The anodic oxidation of 6 was accomplished in a similar manner.
The resulting solution of diarylcarbenium ion 8 exhibited a single
set of 1H NMR signals at -78 °C (Figure 2). A signal at 9.87 ppm
(singlet) is assigned to the proton adjacent to the cationic carbon
(Ha). The solution also exhibited a 13C NMR signal at 193.7 ppm
There is another merit in the use of a silyl group. For the
oxidation of 4b to generate diarylcarbenium ion 5 in the next
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10864 J. AM. CHEM. SOC. 2008, 130, 10864–10865
10.1021/ja803487q CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
yield was not optimized (37%, FAB-MS: m/z calcd for C182H126F16:
2614.9604, found: 2614.9590).
In summary, we have developed a new iterative and convergent
method for making dendritic molecules based on the cation-pool
method. The silyl-substituted diphenylmethane serves as a useful
building block. Development of new building blocks and applica-
tions to synthesis of dendrimers that have various cores and
functional groups exhibiting a variety of functions16 are under way
in our laboratory.
Acknowledgment. This work was partially supported by the
Grant-in-Aid for Scientific Research. The authors thank Dr. Keiko
Kuwata of Kyoto University for MS analysis and Dr. Tetsuaki
Fujiwara of Kyoto University for fruitful discussions.
Figure 2. 1H NMR spectrum of dendritic diarylcarbenium ion 8.
Supporting Information Available: Experimental procedures and
spectroscopic data of compounds. This material is available free of
charge via the Internet at http://pubs.acs.org
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Figure 3. Dendritic molecules synthesized from cation 8.
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C
198H144F16Si: 2853.0764, found: 2853.0782), which can be utilized
for the next sequence. The Friedel-Crafts type reaction with 1,3,5-
trimethoxybenzene gave the disubstituted product 10 in 49% yield
(FAB-MS: m/z calcd for C191H136O3F16: 2781.0234, found:
2781.0198), suggesting that dendritic molecules having various core
structures can be synthesized in a similar manner. Cation 8 is also
useful as a precursor for free radical reactions.15 For example,
cathodic reduction gave homocoupling product 11, although the
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