A novel dendrimer-type m-terphenyl substituent for the kinetic stabilization of highly reactive species

Article abstract of DOI:10.1016/S0040-4039(01)00871-1

A novel m-terphenyl-based steric protection group (Bpq group) bearing a dendrimer-type framework was designed and successfully applied to the stabilization of the corresponding N-thiosulfinylaniline and arenesulfenyl iodide. The Bpq group was found to provide a very inert environment for the reactive functionality embedded in its cleft.

Full text of DOI:10.1016/S0040-4039(01)00871-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4875–4877
A novel dendrimer-type m-terphenyl substituent for the kinetic
stabilization of highly reactive species
Kei Goto,a,* Gaku Yamamoto,a,* Bo Tanb,† and Renji Okazakib,‡
aDepartment of Chemistry, School of Science, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan
bDepartment of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan
Received 27 April 2001; revised 17 May 2001; accepted 18 May 2001
Abstract—A novel m-terphenyl-based steric protection group (Bpq group) bearing a dendrimer-type framework was designed and
successfully applied to the stabilization of the corresponding N-thiosulfinylaniline and arenesulfenyl iodide. The Bpq group was
found to provide a very inert environment for the reactive functionality embedded in its cleft. © 2001 Elsevier Science Ltd. All
rights reserved.
In the kinetic stabilization of reactive species, it is of
great importance to design a reaction environment suit-
able for the stabilization of the target species. Recently,
we have developed a novel bowl-type steric protection
group 1 (denoted as Bmt hereafter), where the central
functionality is surrounded by two m-terphenyl units,
and reported that it is very effective in preventing
reactive species from undergoing dimerization or self-
condensation.1 The use of the Bmt group has enabled
us to successfully synthesize and isolate the reactive
species such as an arenesulfenic acid (ArSOH)1b and an
arenesulfenyl iodide (ArSI)1d as stable crystals; these
species have not been synthesized even by using a bulky
substituent such as the 2,4,6-tri-tert-butylphenyl (Mes*)
group. In some special cases, however, the methylene
groups at ortho-positions of a Bmt group are involved
in the reaction with a functional group in the cavity.
For example, heating of N-thiosulfinylaniline 2 for a
prolonged time resulted in intramolecular cyclization to
afford 2,1-benzisothiozole 3 (Scheme 1).1e Such kind of
intramolecular reaction involving the ortho-alkyl group
is one of the major problems associated with an aro-
matic steric protection group, and similar cyclization
reactions were also reported for N-thiosulfinylanilines
42 and 5.3 Recently, m-terphenyl-2%-yl groups repre-
sented by the general formula 6 have been widely
utilized as excellent steric protection groups which are
not liable to undergo such intramolecular reactions.4
Even in 6, however, the alkyl groups at 2,2¦,6,6¦-posi-
tions are considerably close to the central functionality
and sometimes involved in its reaction.5 We report here
the design of a novel m-terphenyl-based dendrimer-type
substituent 7 (denoted as Bpq hereafter)6 as a more
inert and effective steric protection group and its appli-
N
S
80 °C, 4 d
Ar
Ar
BmtN=S=S
toluene-d8
2
3
(Ar = 2,2",6,6"-tetramethyl-m-terphenyl-2'-yl)
1 ≡ Bmt
Scheme 1.
Keywords: steric protection; m-terphenyl; N-thiosulfinylaniline; arenesulfenyl iodide.
* Corresponding authors. Present address: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan (K.G.); e-mail: goto@chem.s.u-tokyo.ac.jp; gyama@kitasato-u.ac.jp
†
Present address: Department of Chemistry, Tsinghua University, Beijing 100084, China.
Present address: Department of Chemical and Biological Sciences, Faculty of Science, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku,
‡
Tokyo 112-8681, Japan.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00871-1

4876
K. Goto et al. / Tetrahedron Letters 42 (2001) 4875–4877
cation to the synthesis of a stable N-thiosulfinylaniline
and an arenesulfenyl iodide.
even after subsequent heating at 100°C for 7 days in a
sealed tube. Compound 12 is much more stable than
compound 5,3 which has so far been known as the most
stable N-thiosulfinylaniline; 5 was reported to decom-
pose to the corresponding benzisothiazole after 1 week
upon heating at 80°C in benzene. These results clearly
demonstrate that the Bpq group is not only effective for
prevention of the bimolecular decomposition of the
reactive species such as an N-thiosulfinylaniline but
also provides very inert reaction environment to the
species as expected.
In BpqX, the m-terphenyl framework extends like a
dendrimer to form a large molecular cleft. The CPK
model examination indicates that the two biaryl bonds
at the ortho-positions of X can rotate rather freely.
However, in any conformation of the molecule, the
central functionality X is always embedded in the cleft
and its dimerization is expected to be very difficult.
Furthermore, because the skeleton of BpqX consists of
solely rigid biaryl units, the peripheral isopropyl groups
cannot be close to the central functionality X, thus
providing an inert environment without alkyl groups
around X. The framework of BpqX can be readily
constructed by repetition of the Hart’s method for the
m-terphenyl synthesis7 via bromide 8 as shown in
Scheme 2. Quenching the second reaction with
trimethylsilylmethyl azide or iodine afforded amine 9 or
iodide 10, respectively. Iodide 10 was further converted
As another reactive species to be stabilized by a Bpq
group, we synthesized a sulfenyl iodide, which has been
known to be very unstable because of the ready dispro-
portionation reaction (2RSI“RSSR+I2).10 Oxidation
of thiol 11 with an equimolar amount of iodine in the
presence of triethylamine afforded sulfenyl iodide 13 in
92% yield after chromatographic purification (Scheme
3).11 The structure of 13 was established by X-ray
crystallographic analysis (Fig. 1).12 The shortest inter-
1
to thiol 11 via lithiation.8 The signal pattern of the H
NMR spectra indicated that, in compounds 9, 10, and
11, two biaryl bonds at the ortho-positions of the
central functionality rotate rapidly on the NMR time-
scale as expected.
,
molecular S···I distance is 8.69 A, indicating that sul-
fenyl iodide 13 is monomeric in the crystalline state.
The SꢀI functionality is incorporated in the molecular
cleft formed by the rigid dendrimer-type framework
and surrounded by the isopropyl groups from a distance.
The reaction of aniline 9 with disulfur dichloride in the
presence of triethylamine afforded N-thiosulfinylaniline
12, which was isolated by silica-gel chromatography as
red crystalline solids in 85% yield (Scheme 3).9 N-Thio-
sulfinylaniline 12 showed remarkable thermal stability
in comparison with compound 2 bearing a Bmt group.
While 2 underwent intramolecular cyclization reaction
to 3 upon heating in toluene-d8 at 80°C for 4 days in a
sealed tube,1e no decomposition of 12 was observed
after heating in benzene-d6 at 80°C for 11 days and
S2Cl2, Et3N
BpqNH2
BpqN=S=S
Et2O
9
12 (85%)
I2, Et3N
CDCl3
PhCH2NH2
CDCl3
BpqSH
BpqSI
13 (92%)
BpqSNHCH2Ph
11
14 (89%)
Scheme 3.
NSS
R
R
R
R'
R
R
R
6
7 ≡ Bpq
4: R = t-Bu, R' = Me
5: R = R' = CH(SiMe3)2
1) Mg
I
2)
Br
Br
1) Mg
1) Me3SiCH2N3
2) H+
Li
Cl
Cl
BpqNH2
9 (51%)
BpqI
10 (69%)
Br
2)
Br
3) H+
THF
THF
I2
(67%)
Br
8
t-BuLi, S8
THF
LiAlH4
THF
BpqI
10
BpqSH
11 (63%)
Scheme 2.

K. Goto et al. / Tetrahedron Letters 42 (2001) 4875–4877
4877
References
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Figure 1. ORTEP drawing of 13 (30% probability). Selected
,
bond lengths (A) and angles (°): S(1)ꢀI(1), 2.316(4); S(1)ꢀC(1),
1.777(9); I(1)ꢀS(1)ꢀC(1), 103.8(4).
6. Bpq denotes 5%,5§-b
6
is(2,6-diisopropylphenyl)-2,6,2¨,6¨-
6
Thus its disproportionation process is considered to be
extremely difficult. In fact, compound 13 was found to
be stable both in the crystalline state and in solution,
similarly to the sulfenyl iodide bearing a Bmt group.1d
Heating of 13 at 80°C for 12 h in toluene-d8 resulted in
no decomposition, indicating the effectiveness of the
Bpq group again. Treatment of 13 with benzylamine
afforded sulfenamide 14, which demonstrates that there
is a space around the SꢀI functionality large enough for
its reaction with a relatively small reagent such as
tetraisopropyl-m-quinquephenyl-2¦-yl.
6
7. (a) Du, C.-J. F.; Hart, H.; Ng, K.-K. D. J. Org. Chem.
1986, 51, 3162–3165; (b) Saednya, A.; Hart, H. Synthesis
1996, 1455–1458.
8. Thiol 11 was also obtained by quenching the second
reaction of the m-terphenyl synthesis with elemental sulfur
followed by reduction with LiAlH4. However, the products
were much more complex than the reaction starting from
iodide 10, and purification of 11 was difficult.
9. Spectral and analytical data for 12: mp 264–266°C. 1H
NMR (500 MHz, CDCl3) l 1.05 (d, J=6.7 Hz, 24H), 1.13
(d, J=6.7 Hz, 24H), 2.72 (m, 8H), 6.94 (t, J=1.5 Hz, 2H),
7.16 (d, J=1.5 Hz, 4H), 7.17 (d, J=7.6 Hz, 8H), 7.31 (t,
J=7.6 Hz, 4H), 7.48–7.54 (m, 3H); 13C NMR (125 MHz,
CDCl3) l 24.1 (q), 24.2 (q), 30.5 (d), 122.4 (d), 127.9 (d),
128.0 (d), 128.3 (d), 130.0 (d), 130.1 (d), 132.0 (s), 138.5
(s), 138.9 (s), 140.3 (s), 145.7 (s), 146.7 (s). UV–vis (hexane)
umax 345 (m 2830), 468 (640, sh), 557 (160, sh) nm. Found:
C, 83.28; H, 8.17; N, 1.47; S, 6.50%. Calcd for C66 H77NS2:
C, 83.58; H, 8.18; N, 1.48; S, 6.76%. HRMS (FAB): Found
m/z 948.5558. Calcd for C66H78NS2: [M+H]+ 948.5576.
10. (a) Johnson, J. P.; Murchie, M.; Passmore, J.; Tajik, M.;
White, P. S.; Wong, C.-M. Can. J. Chem. 1987, 65,
2744–2755; (b) Klapo¨tke, T.; Passmore, J. Acc. Chem. Res.
1989, 22, 234–240.
1
benzylamine. The H NMR spectra of N-thiosulfinyl-
aniline 12 and sulfenyl iodide 13 showed the same
signal pattern as that of 9, 10, and 11, indicating that
the CꢀN bond of 12 and the CꢀS bond of 13 as well as
the biaryl bonds at the ortho-positions of the central
functionalities of both compounds rotate rapidly on the
NMR time-scale. These results also demonstrate that
there is a large space around the central functionality to
allow free rotation of these bonds.
The application of this novel steric protection group to
the synthesis of other reactive species as well as the
development of further extended dendrimer-type sub-
stituents are currently in progress.
11. Selected spectral data for 13: mp 235–237°C (dec.). 1H
NMR (500 MHz, CDCl3) l 1.09 (d, J=6.9 Hz, 24H), 1.14
(d, J=6.9 Hz, 24H), 2.94 (m, 8H), 7.06 (t, J=1.5 Hz, 2H),
7.18–7.22 (m, 8H), 7.31–7.36 (m, 8H), 7.41–7.50 (m, 3H).
UV–vis (CHCl3) umax 330 (m 4700), 509 (250) nm.
12. Crystal data for 13: C66H77SI·C6H14, FW=1115.48, tri-
Acknowledgements
This work was partly supported by a Grant-in-Aid for
Scientific Research (No. 10740297 (K.G.)) from the
Ministry of Education, Science, Sports and Culture,
Japan, and the Sumitomo Foundation (K.G.). The
authors also thank Shin-etsu Chemical Co., Ltd. and
Tosoh Finechemical Corporation for the generous gifts
of chlorosilanes and alkyllithiums, respectively.
(
clinic, space group P1, a=16.024(5), b=19.251(7), c=
,
11.743(3) A, h=105.70(2), i=100.22(3), k=99.43(3)°,
V=3345(1) A , Z=2, Dcalcd=1.107 g/cm3, v=5.47 cm−1
,
3
,
R (Rw)=0.074 (0.074).
.