Arylthiols as highly chemoselective and environmentally benign radical reducing agents

Article abstract of DOI:10.1021/jo801200b

(Chemical Equation Presented) Arylthiols serve as excellent environmentally benign reducing agents for organotellurium, organostibine, and organobismuthine compounds under radical conditions. Both small molecules and macromolecules possessing these heteroatom groups are reduced under moderate thermal conditions to give near quantitative yields in most cases. The reduction shows high chemoselectivity with respect to the heteroatom compounds; the reactivity decreases in the order alkylbismuthines, alkylstibines, and alkyltellurides, while simple alkyl iodides could not be reduced. Alkyltellurides are selectively reduced in the presence of alkyl iodides even when an excess amount of arylthiol is used. Furthermore, alkylstibines are also selectively reduced in the presence of alkyltellurides. Moreover, the reduction conditions are compatible with the presence of a variety of polar functional groups in the substrates, products, and solvents, which are not tolerant under ionic and metal-catalyzed conditions. Carbon-carbon bond formation is possible with use of the carbon-centered radicals that are generated. The results clearly reveal the synthetic utility of arylthiols in organic synthesis.

Full text of DOI:10.1021/jo801200b

Arylthiols as Highly Chemoselective and Environmentally Benign
Radical Reducing Agents
,
†
‡
Shigeru Yamago* and Atsushi Matsumoto
Institute for Chemical Research, Kyoto UniVersity, Uji, Kyoto 611-0011, Japan, and DiVision of Molecular
Materials Chemistry, Graduate School of Science, Osaka City UniVersity, Osaka 558-8585, Japan
yamago@scl.kyoto-u.ac.jp
ReceiVed June 10, 2008
Arylthiols serve as excellent environmentally benign reducing agents for organotellurium, organostibine,
and organobismuthine compounds under radical conditions. Both small molecules and macromolecules
possessing these heteroatom groups are reduced under moderate thermal conditions to give near quantitative
yields in most cases. The reduction shows high chemoselectivity with respect to the heteroatom compounds;
the reactivity decreases in the order alkylbismuthines, alkylstibines, and alkyltellurides, while simple
alkyl iodides could not be reduced. Alkyltellurides are selectively reduced in the presence of alkyl iodides
even when an excess amount of arylthiol is used. Furthermore, alkylstibines are also selectively reduced
in the presence of alkyltellurides. Moreover, the reduction conditions are compatible with the presence
of a variety of polar functional groups in the substrates, products, and solvents, which are not tolerant
under ionic and metal-catalyzed conditions. Carbon-carbon bond formation is possible with use of the
carbon-centered radicals that are generated. The results clearly reveal the synthetic utility of arylthiols in
organic synthesis.
Introduction
SCHEME 1. Radical-Mediated Reduction of
Organoheteroatom Compounds by Metal Hydride
The radical-mediated reduction of organoheteroatom com-
pounds (R-X), such as organohalogens and organochalcogens,
1
-4
has been widely used in organic synthesis (Scheme 1).
Tributyltin hydride (M ) SnBu3) has been most extensively
used for this purpose because it readily donates hydrogen to
carbon-centered radicals giving reduction products (step 2).
Furthermore, the high reactivity of the resulting tin radical allows
heteroatoms to be abstracted from organochalcogens or orga-
nohalides to generate carbon-centered radicals (step 1) in a
radical chain reaction.
5,6
However, the development of alternative reducing agents is
strongly desired because of the environmental concerns involved
3
,7
in using organotin compounds. For this reason alternative
reducing agents such as tris(trimethylsilyl)silane and hydrogen
*
To whom correspondence should be addressed.
Kyoto University.
Osaka City University.
8
†
‡
(
1) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; WILEY-
VCH: Weinheim, Germany, 2001.
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UK, 1991; Vol. 4.
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Butterworths: London, UK, 1987.
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(
(
(
3) Studer, A.; Amrein, S. Synthesis 2002, 835–849.
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9
9, 1991–2070.
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7
300 J. Org. Chem. 2008, 73, 7300–7304
10.1021/jo801200b CCC: $40.75  2008 American Chemical Society
Published on Web 08/27/2008

Arylthiols as EnVironmentally Benign Radical Reducing Agents
9
,10
phosphates
efficient reducing agents possessing metal-hydrogen bonds,
18
have been developed, and a search for new and
TABLE 1. Reduction of Tellanylglycoside 1 with Various Thiols
11-13
14
15
16,17
such as Ge-H,
Ga-H, In-H, Zr-H,
and Cr-H,
1
9,20
is ongoing.
Thiols are excellent hydrogen donors in radical reactions, but
their use in the reduction of organohalogens has so far been
unsuccessful due to the poor reactivity of thiyl radicals toward
a
run
RSH
PhSH
temp (°C)
yield (%)
2
1
1
2
3
4
5
6
7
8
9
80
80
80
80
80
80
80
80
80
100
85
88 (100)
85 (100)
79 (100)
74 (100)
83 (100)
72 (100)
56 (100)
79 (100)
67 (100)
94 (100)
98 (100)
the abstraction of halogen atoms (step 1). Therefore, thiols
can reduce organohalogens only in the presence of silanes as
p-MeC6H4SH
p-MeOC6H4SH
p-HOC6H4SH
p-ClC H SH
2
2-24
25,26
polarity reversal catalysts
or by using silylthiols,
thus
their synthetic applications have been limited.
In contrast, we have recently reported that benzenethiol is
6
4
p-CF3C6H4SH
p-NO2C6H4SH
C6F5SH
n-C8H17SH
PhSH
able to reduce tellanylglycoside 1 with high efficiency under
27
photoirradiation. The reaction of organostibines and bismuth-
b
ines with benzenethiol to give phenylthiostibines and bismuth-
10
2
8
c
ines has also been reported. Although the fate of the carbon
residues derived from the organostibines and bismuthines was
not described in this study, it is probable that the reduction
products were formed.
11
PS-thiophenol
a
Determined by 1H NMR. The number in parentheses is the yield
based on the amount of 1 converted. PhSH (2 equiv) was used in the
presence of ACHN [1,1-azobis(cyclohexane-1-carbonitrile)] instead of
AIBN. The 10-h half-life decomposition temperatures of ACHN and
AIBN are 88 and 65 °C in toluene, respectively. Five equivalents of
polymer-supported thiophenol [3-(3-mercaptophenyl)propaneamidomethyl po-
lystyrene] was used.
b
Despite these results, the synthetic efficiencies of thiols as
reducing agents for organoheteroatom compounds are still
unknown. These studies prompted us to examine the versatility
of the thiol reduction of various organoheteroatom compounds
c
2
9-48
49,50
including organotellurides,
organostibines,
and orga-
5
1
nobismuthines under thermal conditions. These heteroatom
compounds have recently been recognized as excellent precur-
sors of carbon-centered radicals for the precision synthesis of
both small molecules and macromolecules. The development
of mild and environmentally benign reducing agents would
greatly facilitate the use of these heteroatom compounds in
organic and polymer synthesis.
(
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Results and Discussion
(
The substituent effect of thiols in the reduction was examined
with tellanylglycoside 1 as a model substrate (Table 1). A
solution of 1, AIBN (0.1 equiv), and benzenethiol (1.4 equiv)
was heated in toluene at 80 °C for 1 h, and the desired product
2 was formed in 88% yield together with a 12% recovery of 1,
1
1
1
1
(
(
(
18) Smith, D. M.; Pulling, M. E.; Norton, J. R. J. Am. Chem. Soc. 2007,
29, 770–771.
1
as determined by H NMR (Table 1, run 1). The reduction
(
(
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20) Pozzi, D.; Scanlan, E. M.; Renaud, P. J. Am. Chem. Soc. 2005, 127,
proceeded smoothly in various nonpolar and polar solvents
including trifluoromethylbenzene, dimethyl formamide, propi-
onitrile, and 2-butanone. Arylthiols with both electron-donating
and withdrawing substituents at the para-position of the aryl
group tended to decrease the reactivity more than benzenethiol
1
4204–14205.
21) Sulfur-Centered Radicals; Bertrand, M. P., Ferreri, C., Eds.; WILEY-
VCH: Weinheim, Germany, 2001; Vol. 2.
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(
22) Roberts, B. P. Chem. Soc. ReV. 1999, 28, 25–35.
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989, 1387–1388.
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Perkin Trans. 1 1991, 103–112.
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J. Chem. Soc., Chem. Commun. 1991, 586–587.
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342.
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2524–2526.
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(43) Yamago, S.; Iida, K.; Yoshida, J. J. Am. Chem. Soc. 2002, 124, 2874–
2875.
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4
(
(
2
(
(
(
(
(
28) Davies, A. G.; Hook, S. C. W. J. Chem. Soc. B 1970, 4, 735–737.
29) Yamago, S. Synlett 2004, 1875–1890.
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31) Yamago, S. Proc. Jpn. Acad., Ser. B 2005, 81, 117–128.
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Yoshida, J. J. Am. Chem. Soc. 2003, 125, 8720–8721.
(46) Yusa, S.; Yamago, S.; Sugahara, M.; Morikawa, S.; Yamamoto, T.;
Morishima, Y. Macromolecules 2007, 40, 5907–5915.
(47) Sugihara, Y.; Kagawa, Y.; Yamago, S.; Okubo, M. Macromolecules
2007, 40, 9208–9211.
Russell, C. G.; Singh, A.; Wong, C. K.; Curtis, N. J. J. Am. Chem. Soc. 1980,
02, 4438–4447.
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R. I. J. Am. Chem. Soc. 1994, 116, 8937–8951.
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Kwak, Y.; Goto, A.; Fukuda, T. J. Am. Chem. Soc. 2004, 126, 13908–13909.
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J. Org. Chem. Vol. 73, No. 18, 2008 7301

Yamago and Matsumoto
SCHEME 3. Chemoselectivity of Thiol Reduction
SCHEME 2. Formation and Stability of
Phenyl(p-tolyltellanyl)sulfane
TABLE 2. aReduction of Organoheteroatom Compounds with
Benzenethiol
azo
PhSH conditions
yield
(%)
b
c
run
substrate
initiator (equiv) (°C/h)
product
1
2
3
4
5
6
7
8
9
n-C12H25TePh
i-PrTePh (3)
t-BuTePh (4)
PhCH(Me)TeMe
Me2C(CO2Et)TeMe none
Me2C(CN)TeMe (5) AIBN
PhCOTeMe
(n-C12H25)3Sb
i-Pr3Sb (6)
V-30
ACHN 2.0
none
none
5.0
120/2
100/5
30/1
30/1
30/1
80/1
100/5
80/0.5 n-C12H26
80/0.5 i-PrH
30/1
80/8
120/5
30/1
80/5
120/5
80/2
n-C12H26
37
99
100
100
i-PrH
t-BuH
PhEt
Me2CHCO2Et 100
Me2CHCN
PHCHO
1.2
1.2
1.2
1.2
100
95
296
295
2
sp carbon-tellurium bonds in aryltellurides are inert under
ACHN 5.0
AIBN
AIBN
d
d
these conditions, and selective and quantitative reduction of the
3.5
3.5
1.1
1.2
5.0
1.1
1.1
5.0
1.4
3
sp carbon-tellurium bond occurred. An acyl telluride, which
2
1
1
1
1
1
1
1
0 Me2C(CO2Et)SbMe2 none
Me2CHCO2Et 100
Me2CHCN
t-BuPh
Me2CHCO2Et 100
Me2CHCN
possesses an sp carbon-tellurium bond yet liberates a stabilized
1 Me2C(CN) SbMe2
2 (t-BuC6H4)3Sb
3 Me2C(CO2Me)BiMe2 none
4 Me2C(CN) BiPh2
5 (t-BuC6H4)3Bi
6 EtOCOCH2I
none
V-30
99
<6
acyl radical, was efficiently reduced to the corresponding
aldehyde (run 7). Polar functional groups in the substrates and/
or products, such as aldehyde, ester, and cyano groups, were
not affected because the reaction proceeded under neutral
conditions.
none
V-30
AIBN
100
288
d
t-BuPh
EtOCOCH3 100
a
We next examined the reduction of organostibines and
organobismuthines, and found that these heteroatom compounds
were also excellent substrates (Table 2, runs 8-15). It should
be noted that the thiol reduction of these compounds takes place
much faster than that of organotellurium compounds. Thus, both
primary and secondary alkylstibines were reduced at 80 °C. All
The reaction was carried out by heating a solution of the substrate
with benzenethiol in the presence or absence of an azo-initiator (0.1
equiv) in C6D6 or toluene. V-30: 2-(carbamoylazo)isobutyronitrile. The
0-h half-life decomposition temperature of V-30 is 104 °C in toluene.
Determined by H NMR or GLC. Yield based on an assumption that
mol of substrate generates 3 mol of reduction products.
b
1
c
1
d
1
3
of the sp carbon-antimony bonds in trialkylstibines were
reduced virtually quantitatively (runs 8 and 9). tert-
(
runs 2-8). Because the rate-determing step is the abstraction
of the tolyltellanyl group by the thiyl radical (step 1 in Scheme
), this step is slightly affected by the electronic effects. An
alkylthiol also showed lower reactivity than benzenethiol (run
). Better results occurred with the use of 2 equiv of ben-
zenethiol at 100 °C (run 10). Polymer-supported thiophenol was
also effective and gave 2 in quantitative yield (run 11).
The reduction by benzenethiol also generated a byproduct,
which was tentatively identified as phenyl(p-tolyltellanyl)sulfane
Alkyl-antimony bonds were also effectively reduced at 30-80
°C. The reduction occurred selectively at the carbon-antimony
bond to liberate most stable radicals when unsymmetrical
substrates were used, and gave the reduction products in
quantitative yields by employing 1 equiv of benzenethiol (runs
10 and 11). tert-Alkyl-bismuth bonds were also reduced
quantitatively under mild conditions (runs 13 and 14). The
aryl-antimony bond could not be reduced even at 120 °C (run
12), but the aryl-bismuth bond was reduced quantitatively under
the same conditions (run 15). While simple alkyl iodides were
shown to be completely inert in benzenethiol (vide infra), an
iodide possessing a radical-stabilizing ester group at the
R-carbon position was successfully reduced in quantitative yield
(run 16).
The high chemoselectivity of the current reduction process
should be emphasized. Benzenethiol was completely unable to
reduce tert-butyl iodide (7), tert-butyl bromide, or tert-butyl
phenyl selenide under similar conditions. Indeed, a competition
experiment in which the reduction of a mixture of tert-butyl
phenyl telluride (4) and 7 was attempted resulted in the selective
reduction of 4, even when 2 equiv of benzenethiol was
employed. Iodide 7 was recovered completely intact (Scheme
3a). In contrast, the same competition experiment with 1 equiv
of tributyltin hydride took place nonselectively, leaving equal
amounts of unreacted 4 and 7. A competition experiment
involving tri-isopropylstibine (6) and isopropyl phenyl tel-
luride (3) resulted in the selective reduction of 6 (Scheme
3b). These results indicate that thiols can be used as highly
chemoselective reducing agents.
1
9
1
by H NMR spectroscopy in an experiment carried out in C6D6.
However, this compound is thermally labile and underwent
disproportionation to ditolyl ditelluride and diphenyl disulfide
(
Scheme 2). Equilibrium was finally reached, at which the so-
lution contained a 25:75 ratio of the tellanylsulfane and the
ditelluride/disulfide mixture. The ditelluride and disulfide were
both isolated in pure form by silica gel chromatography, but
attempts to isolate the tellanylsulfane were unsuccessful because
it is unstable under the chromatography conditions.
The synthetic scope of the thiol reduction was examined by
using various organoheteroatom compounds with benzenethiol,
and the results are summarized in Table 2. The required reaction
conditions strongly depend on the stability of the carbon-
centered radicals that are liberated from the substrates. Thus,
while the reduction of simple primary alkyl tellurides was slow
and did not complete within a reasonable period of time even
with 5 equiv of benzenethiol (Table 2, run 1), secondary alkyl
tellurides were reduced almost quantitatively at 100 °C with 2
equiv of benzenethiol (run 2). The reduction of simple tert-
alkyl tellurides and of tellurides possessing a radical-stabilizing
group at the R-carbon position took place quantitatively even
at room temperature in the absence of AIBN (runs 3-6). We
could not observe the formation of benzene derived from the
reduction of benzenetellanyl group (runs 1 and 2). Therefore,
The above results clearly indicate that the reactivity of the
organoheteroatom compounds decreases in the order bismuth-
ines, stibines, tellurides, and iodides. This order of reactivity is
7
302 J. Org. Chem. Vol. 73, No. 18, 2008

Arylthiols as EnVironmentally Benign Radical Reducing Agents
SCHEME 4. Reductive Intramolecular Cyclization
To verify the reaction mechanism, intramolecular cyclization
was examined by using the organotellurium compound 10
4
0
(
Scheme 4). When 10 was treated with benzenethiol in the
presence of 1,1′-azobis(cyclohexane-1-carbonitrile) (ACHN), the
cyclized product 12 was formed in 86% yield with complete
cis-selectivity with respect to the ring junction and with 1:2.3
endo/exo selectivity for the benzilic position. The selectivity
was identical with that obtained from the tributyltin hydride-
promoted cyclization of 10 within an experimental error with
an endo/exo ratio of 1:2.2. These results clearly indicate that
the thiol reduction also proceeds via radical intermediate 11.
Conclusion
Arylthiols serve as excellent reducing agents for organotel-
lurium, stibine, and bismuthine compounds. The mild reaction
conditions, high yields, and high chemoselectivity of this
reduction method suggest that it will find many synthetic
applications in radical-mediated synthetic transformations.
FIGURE 1. (a) Synthesis and (b) TOF-MS spectrum of ω-end-reduced
polystyrene 8. Molecular ion mass, as indicated by the average mass
number, is observed as the silver ion-added form (M + Ag) . The MS
analysis indicated 1.4% formation of R,ω-(2-cyano-2-propyl)-substituted
polystyrene, which formed by the coupling of the polymer-end radical
with 2-cyano-2-propyl radical generated from AIBN.
+
Experimental Section
Typical Experimental Procedure for the Reduction of Tel-
lanyl Glycoside 1: Synthesis of 1-Deoxy-2,3,4,6-tetra-O-acetyl-
5
4
ꢀ
-D-glucopyranoside (2). Benzenethiol (30.9 mg, 0.28 mmol)
55
identical with that observed in the homolytic substitution
reaction of heteroatom compounds with carbon-centered radicals
was added to a solution of 1 (110.0 mg, 0.20 mmol) and AIBN
(3.3 mg, 0.02 mmol) in toluene (0.6 mL) under a nitrogen
atmosphere, and the resulting reaction mixture was heated at 80
4
5,51,52
49,53
obtained experimentally
and computationally,
and is
°
3
C for 1 h. The solvent was removed in vacuo, and CDCl and
consistent with the rate-determining step of the reduction being
the abstraction of the heteroatom from the substrate (step 2 in
Scheme 1). However, the difference in reactivity toward carbon-
centered radicals is relatively small (the reactivity differs by
1
,1,2,2-tetrachloroethane (10.5 µL; an internal standard) were
introduced. The reduction product 2 was formed in 88% yield
together with a 12% recovery of 1, as determined by H NMR
1
analysis. The pure product 2 was obtained by flash chromatography
4
9,51,52
no more than ten times),
and further investigation is
1
on silica gel, using 35% ethyl acetate/hexane as an eluent. H NMR
required to clarify the origin of the extremely large difference
in reactivity with respect to reduction.
(
3
400 MHz, CDCl ) δ 2.02-2.05 (m, 9 H), 2.10 (s, 3 H), 3.31
(t, J ) 10.8 Hz, 1 H), 3.60 (ddd, J ) 10.0, 4.8, 2.4 Hz, 1 H), 4.13
The synthetic utility of the thiol reduction was further
examined by carrying out the reduction of the heteroatom group
of a polymer end. Polystyrene 8 bearing a methyltellanyl group
at the ω-end of the polymer was prepared from organotellurium
compound 5 and 30 equiv of styrene in the presence of AIBN
(dd, J ) 12.8, 2.4 Hz, 1 H), 4.16 (dd, J ) 11.2, 5.6 Hz, 1 H), 4.21
(
dd, J ) 12.4, 4.8 Hz, 1 H), 5.02 (ddd, J ) 10.4, 10.0, 5.6 Hz, 1
H), 5.04 (t, J ) 9.6 Hz, 1 H), 5.21 (t, J ) 9.6 Hz, 1 H).
Typical Experimental Procedure for the Reduction When a
Volatile Product Is Generated: Reduction of Isopropylphenyl-
telluride (3). A solution of 3 (49.6 mg, 0.20 mmol), benzenethiol
4
5
(
Figure 1a). It was reduced with benzenethiol (1.2 equiv) at
(
6 6
44.1 mg, 0.40 mmol), and ACHN (4.9 mg, 0.02 mmol) in C D
0.6 mL) was heated at 100 °C for 5 h in a sealed NMR tube. The
8
2
0 °C for 1 h to give end-protonated polystyrene 9 with Mn )
(
800 and PDI ) 1.12, where Mn is the number-average
1
H NMR analysis indicated the complete disappearance of 3 and
1
molecular weight and PDI is the polydispersity index obtained
by the gel permeation chromatography analysis. When matrix-
assisted laser desorption ionization time-of-flight (MALDI-TOF)
mass spectroscopy was carried out on 9, the selective formation
of end-reduced polystyrene was revealed (Figure 1b). In view
of the apparently high reactivities of organostibines and bis-
muthines, we expect that polymer end groups possessing these
heteroatoms would also be reduced by benzenethiol.
the formation of propane in 99% yield. H NMR (400 MHz, C D )
6
6
0.85 (t, J ) 7.2 Hz, 6 H), 1.25 (sept, J ) 7.2 Hz, 2 H).
Synthesis of End-Reduced Polystyrene 9. Polystyrene 8 was
prepared by heating a solution of 5 (21.1 mg, 0.10 mmol), AIBN
(
16.9 mg, 0.10 mmol), and styrene (312.5 mg, 3.0 mmol) at 60 °C
45
for 12 h under a nitrogen atmosphere in a glovebox. A small
portion of the reaction mixture was withdrawn and dissolved in
3
CDCl . The conversion of the monomer (98%) was determined by
(
54) Beckwith, A. L. J.; Duggan, P. J. J. Chem. Soc., Perkin Trans. 2 1993,
1673–1679.
(55) Yamago, S.; Kokubo, K.; Masuda, S.; Yoshida, J. Synlett 1996, 929–
930.
(
52) Kwak, Y.; Goto, A.; Fukuda, T.; Yamago, S.; Ray, B. Z. Phys. Chem.
005, 219, 283–293.
53) Schiesser, C. H.; Wild, L. M. Tetrahedron 1996, 52, 13265–13314.
2
(
J. Org. Chem. Vol. 73, No. 18, 2008 7303

Yamago and Matsumoto
1H NMR. Trifluoromethylbenzene (1.0 mL) was added to the rest
of the reaction mixture, which was shaken until it became a
homogeneous solution. Benzenethiol (13.2 mg, 0.12 mmol) was
added, and the resulting mixture was heated at 80 °C for 2 h. The
mixture was poured into methanol (200 mL) with vigorous stirring.
The precipitate was collected by filtration and dried under reduced
pressure at 40 °C to give 280.1 mg of polystyrene (90% yield).
chromatography (5% ethyl acetate/hexane) followed by preparative-
recycling GPC afforded 11 as a 1:2.2 mixture in 86% yield (185.1
mg). The same experiment performed with Bu SnH instead of PhSH
3
gave 11 in 88% yield as a 1:2.2 mixture of endo and exo isomers
by the GC analysis. IR (neat) 705, 760, 920, 940, 1030, 1060, 1460,
20
1500, 1720, 2870, 2940; HRMS (GC-MS, EI) m/z calcd for C15H O
+
1
(M) , 215.1436, found 215.1430 (endo), 215.1430 (exo); H NMR
(400 MHz, CDCl ) δ 1.06-1.42 (m, 3.0 H), 1.41-1.64 (m, 3.7
Analytical GPC indicated that the polymer formed with M
n
) 2800
3
and PDI ) 1.12. The MALDI-TOF MS analysis indicated the
H), 1.68-1.90 (m, 2.0 H), 1.93-2.01 (m, 0.3 H, endo), 2.24-2.34
(m, 0.7 H, exo), 2.55-2.65 (m, 0.3 H, endo), 2.597 (dd, J ) 14.0,
8.4 Hz, 0.7 H, exo), 2.66-2.81 (m, 0.7 H, endo), 2.772 (dd, J )
14.0, 7.6 Hz, 0.7 H, exo), 3.527 (dd, J ) 8.8, 4.8 Hz, 0.7 H, exo),
3.65 (dd, J ) 10.0, 8.4 Hz, 0.3 H, endo), 3.90 (t, J ) 8.4 Hz, 0.3
H, endo), 3.93-3.99 (m, 0.3 H, endo), 4.017 (dt, J ) 4.8, 4.4 Hz,
0.7 H, exo), 4.073 (t, J ) s8.4 Hz, 0.7 H, exo), 7.14-7.25 (m, 3
formation of the end-protonated polystyrene with M
PDI ) 1.04.
n
) 2600 and
trans-2-Phenyltellanylcyclohexyl Cinnamyl Ether (10). Sodium
hydride (0.56 g, 60% mineral oil dispersion, 14 mmol) was placed
in a dry, two-necked round-bottomed flask, which was flushed with
nitrogen. The mineral oil was washed off by adding anhydrous
hexane (2 mL), which was withdrawn after stirring. This procedure
was repeated three times. Anhydrous THF (30 mL) and 2-hydroxy-
1
3
H), 7.26-7.32 (m, 2 H); C NMR (100 MHz, CDCl
3
) δ 20.4 (CH
, endo), 23.6 (CH , exo), 24.5
, exo), 28.6 (CH , endo),
2
,
endo), 21.1 (CH
(CH , endo), 27.4 (CH
33.5 (CH
exo), 45.5 (CH, endo), 45.6 (CH, exo), 70.9 (CH
2
, exo), 22.1 (CH
2
2
56
cyclohexyl phenyl telluride were added at room temperature, and
the resulting mixture was stirred for approximately 2 h at room
temperature. (E)-Cinnamyl bromide (2.37 g, 12 mmol) was added,
and the resulting solution was stirred for 14 h. Water was added,
and the organic phase was extracted with hexane. The combined
2
2
, exo), 28.3 (CH
2
2
2
, endo), 39.7 (CH
2
, exo), 39.9 (CH, endo), 42.9 (CH,
2
, endo), 71.9 (CH ,
2
exo), 76.1 (CH, exo), 78.3 (CH, endo), 125.9 (CH, exo), 126.0 (CH,
endo), 128.37 (CH, exo), 128.40 (CH, endo), 128.7 (CH, exo), 128.9
(CH, endo), 140.6 (C, exo), 140.9 (C, endo). The stereochemistry
of the ring junction was determined by analogy with structurally
organic phase was washed with saturated aqueous NH
and saturated aqueous NaCl solution, dried over MgSO
4
Cl solution
, and
4
3
8
filtrated. The solvent was removed in vacuo, and the residue was
purified by flash chromatography (2% ethyl acetate/hexane followed
by 5% ethyl acetate/hexane) to afford 3.40 g (81%) of 10 as a light
related 4-substituted 2-oxa-bicyclo[3.4.0]nonane derivatives and
NOESY experiments, and the stereochemistry of the 4-position by
NOESY experiments as shown below. Cross peaks are observed
1
10
10′
5
yellow oil. IR (neat) 693, 735, 968, 1075, 1020, 1433, 1447, 1575,
between H -H , H and H -phenyl ortho-protons in the cis-
1 4
+
2
4
1
1
860, 2940, 3030, 3070; HRMS (EI) m/z calcd for C21
H24OTe (M) ,
exo-isomer and between H -H in the cis-trans-isomer.
1
3
22.0889, found 422.0910; H NMR (400 MHz, CDCl ) δ
.14-1.38 (m, 3 H), 1.48-1.62 (m, 2H), 1.75-1.86 (m, 1H),
.90-2.00 (m, 1 H), 2.11-2.22 (m, 1 H), 3.48 (dt, J ) 9.2, 4.0
Hz, 1 H), 3.60 (ddd, J ) 10.8, 9.2, 4.0 Hz, 1 H), 4.12 (ddd, J )
2.8, 6.0, 1.2 Hz, 1 H), 4.30 (ddd, J ) 12.8, 6.0, 1.2 Hz, 1 H),
.29 (dt, J ) 16.0, 6.0 Hz, 1 H), 6.60 (d, J ) 16.0 Hz, 1 H),
.14-7.35 (m, 6 H), 7.37-7.43 (m, 2 H), 7.80-7.86 (m, 2 H);
1
3
3
) δ 24.0 (CH
2 2
), 27.4 (CH ), 32.2
2
2
), 69.3 (OCH ), 82.5 (TeCH), 111.3
2
Acknowledgment. This work was partly supported by a
Grant-in-Aid for Scientific Research from the Japan Society for
the Promotion of Science. We thank Dr. Takeshi Yamada and
Mr. Eiichi Kayahara of Kyoto University for experimental
assistance, Prof. Masaru Nakahara and Dr. Ken Yoshida of
Kyoto University for the stereochemical assignment of com-
pound 11, and Messrs. Hikaru Umemoto and Takeshi Ka-
meshima of Otsuka Chemical Co. for the TOF-MS measurement.
4
-Benzyl-2-oxabicyclo[3.4.0]nonane (12). Benzenethiol (30.9
mg, 0.28 mmol) was added to a solution of 10 (84.0 mg, 0.20 mmol)
and ACHN (4.9 mg, 0.02 mmol) in toluene (2.0 mL) under a
nitrogen atmosphere, and the resulting reaction mixture was heated
at 100 °C for 6 h. ACHN (9.8 mg, 0.04 mmol) was added in two
portions (0.02 mmol each after 2 and 4 h) during the reaction. The
solvent was removed in vacuo, and CDCl
an internal standard for GC analysis), and 1,1,2,2-tetrachloroethane
10.5 µL, an internal standard for H NMR analysis) were added.
The cyclized product 12 formed as a 1:2.3 mixture of two isomers
as determined by the GC analysis, and 10 was recovered in 14%
yield as determined by the H NMR analysis. Purification by flash
3
, hexadecane (10.0 µL,
1
(
Supporting Information Available: Synthesis and reduction
of organotellurium, stibine, and bismuthine substrates and NMR
spectra for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
1
(
56) White, J. M.; Lambert, J. B.; Spiniello, M.; Jones, S. A.; Gable, R. W.
Chem. Eur. J. 2002, 8, 2799–2811.
JO801200B
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304 J. Org. Chem. Vol. 73, No. 18, 2008