A new approach to 4-aryl-1,3-butanediols by cobalt-catalyzed sequential radical cyclization-arylation reaction of silicon-tethered 6-iodo-1-hexene derivatives

Article abstract of DOI:10.1055/s-2006-951508

Treatment of 6-iodo-4-oxa-3-sila-1-hexene derivatives with arylmagnesium bromide in the presence of a catalytic amount of a cobalt-diamine complex in THF afforded the corresponding benzyl-substituted oxasilacyclopentanes in good yield. The products were converted to 4-aryl-1,3-diols after Tamao-Fleming oxidation. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-951508

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LETTER
3061
A New Approach to 4-Aryl-1,3-butanediols by Cobalt-Catalyzed Sequential
Radical Cyclization–Arylation Reaction of Silicon-Tethered 6-Iodo-1-hexene
Derivatives
New
A
pproac
h
to
i
4-Aryl-
d
1,3-butanedi
e
ols nori Someya, Azusa Kondoh, Akinori Sato, Hirohisa Ohmiya, Hideki Yorimitsu,* Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku,
Kyoto 615-8510, Japan
Fax +81(75)3832438; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received 19 April 2006
Dedicated to Professor Richard Heck
cyclization–arylation protocol3 yields oxasilacyclopen-
Abstract: Treatment of 6-iodo-4-oxa-3-sila-1-hexene derivatives
tanes. Finally, Tamao–Fleming oxidation4 affords 4-aryl-
1,3-butanediols. Without our cobalt-catalyzed protocol,
with arylmagnesium bromide in the presence of a catalytic amount
of a cobalt–diamine complex in THF afforded the corresponding
benzyl-substituted oxasilacyclopentanes in good yield. The prod-
synthesis of 4-aryl-1,3-diols via the conventional silicon-
ucts were converted to 4-aryl-1,3-diols after Tamao–Fleming oxi- tethered strategy using the tin-based radical reaction2a,c
dation.
necessitates (2-arylethenyl)chlorodimethylsilanes that are
not readily available. The present route admits variety in
the aryl groups by simply changing the aryl Grignard re-
agents used.
Key words: 1,3-diols, cobalt, arylation, radical reaction, silicon
1,3-Diol units are often observed in natural products, and
can be oxidized into 1,3-diketones or naturally occurring
polyketides. The synthesis of 1,3-diols is thus widely in-
vestigated.1 In light of the importance of the 1,3-diols,
here we disclose a new approach to 4-aryl-1,3-butanediols
starting from epoxides. As outlined in Scheme 1, ring
opening of epoxides with iodide followed by silylation
with chlorodimethylvinylsilane provides silicon-tethered2
6-iodo-1-hexene derivatives. Our cobalt-catalyzed radical
We first chose cyclohexene oxide as the starting material.
Cyclohexene oxide underwent ring opening by the action
of lithium iodide and acetic acid in THF to give 2-iodo-1-
cyclohexanol.5 Treatment of the crude vic-iodohydrin
with chlorodimethylvinylsilane in the presence of tri-
ethylamine in dichloromethane provided silicon-tethered
substrate 2 in 100% overall yield. Phenylative cyclization
of 2 under the catalysis of [CoCl2 (1)] afforded 3a in
excellent yield (Scheme 2).
R1
OH
R1
OH
Ar
O
R2
R2
AIBN,
Bu3SnH
R1
O
I
(ArCH=CH)Me2SiCl
SiMe2
Ar
HI
H2O2
conventional
R2
route
R1
O
R1
R2
OH
I
SiMe2
R2
Ar
Co cat.
ArMgBr
R1
R2
O
I
(CH2=CH)Me2SiCl
SiMe2
this work
Scheme 1
CoCl2 (5 mol%)
racemic 1 (24 mol%)
PhMgBr (0.75 mmol)
Me
Me
O
I
NMe2
NMe2
O
Me
Si
Si
Me
Ph
THF, 25 °C, 15 min
2 (0.5 mmol)
racemic 1
3a 93%
Scheme 2
SYNLETT 2006, No. 18, pp 3061–3064
0
3
.1
1
.2
0
0
6
Advanced online publication: 25.10.2006
DOI: 10.1055/s-2006-951508; Art ID: S09306ST
© Georg Thieme Verlag Stuttgart · New York

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3062
H. Someya et al.
LETTER
A variety of aryl Grignard reagents were employed for the alkyl iodide 8a serves as a substrate to provide the diol 10
coupling reaction (Scheme 3). All the corresponding in 66% yield. The substrate 8b bearing a diphenylvinylsi-
products could be easily transformed to diols 4 after oxi- lyl group participated in the cyclization. Unfortunately,
dation with alkaline hydrogen peroxide. Not only phenyl- the use of the corresponding bromides as substrates gave
magnesium bromide but also 4-methoxy- and 3- the desired products in no more than 5% yield.
trifluoromethylphenylmagnesium bromides participated
OH
in the reaction. Methyl substitution at the 2-position did
not retard the reaction. The cyclization–arylation with 2-
naphthyl Grignard reagent proceeded smoothly. Employ-
ing mesityl Grignard reagent did not give a satisfactory re-
sult. The products were always 1:1 mixtures of
diastereomers, which originate from the relationship be-
tween the cis-fused bicyclic system and arylmethyl group.
Me
O
O
Me
Me
Me
cat. Co
Si
[O]
Si
OH
Ph
PhMgBr
I
Ph
7
6
5
73% (2:1)
Hex
OH
R
Hex
O
Hex
I
O
R
R
cat. Co
Si
[O]
Si
OH
Ph
OH
R
KF, KHCO3,
30% aq H2O2
ArMgBr
cat. CoCl2/racemic 1
PhMgBr
Ph
OH
Ar
2
3
8a,b
THF, 25 °C, 15 min
9a,b
MeOH–THF (1:1)
10
(1:1)
R = Me (8a) 66% yield from 8a
R = Ph (8b) 68% yield from 8b
4 (1:1)
a: Ar = Ph, 74% yield
b: Ar = 2-naphthyl, 61% yield
c: Ar = 2-MeC6H4, 73% yield
Scheme 4
d: Ar = 4-MeOC6H4, 41% yield
e: Ar = 3-CF3C6H4, 44% yield
The new approach to 4-aryl-1,3-butanediols is applicable
for the construction of an intermediate 16a in the synthe-
sis of 18, an antagonist of human CCR5 receptor.6 The
synthesis is outlined in Scheme 5. Construction of the ep-
oxide group in 13 was performed from 11 in two steps.
Ring opening of epoxide 13 with iodide followed by sily-
lation with chlorodimethylvinylsilane provided silicon-
Scheme 3
Other silicon-tethered substrates, similarly prepared from
the corresponding epoxides, were examined (Scheme 4).
The reaction of iodide 5 with five-membered ring showed
higher diastereoselectivity than that of 2. The primary
O
OHC
Me3S+(O)I–, NaH
PCC
HO
NBoc
NBoc
NBoc
CH2Cl2, r.t.
70%
DMSO, r.t.
61%
12
13
11
Me Me
Me
cat. CoCl2
Me
cat. racemic 1
Si
O
1) LiI, MeCOOH
THF, r.t.
Si
O
ArMgBr
2) (CH2=CH)Me2SiCl
Et3N, CH2Cl2, r.t.
67% in 2 steps
THF, 25 °C
15 min
Ar
I
NBoc
NBoc
14
15
N
N
OH OH
Tamao–Fleming oxidation
NH
Ar
NBoc
16
17
from 16a
a: Ar = Ph, 83% yield from 14
b: Ar = 2-naphthyl, 58% yield from 14
c: Ar = 2-MeC6H4, 39% yield from 14
N
COOH
N
N
N
F
18
Scheme 5
Synlett 2006, No. 18, 3061–3064 © Thieme Stuttgart · New York

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LETTER
New Approach to 4-Aryl-1,3-butanediols
3063
tethered 6-iodo-1-hexene derivatives 14 in 67% overall
yield. Treatment of 14 under the cobalt-catalyzed condi-
tions led to sequential radical cyclization–cross-coupling
reaction to afford a phenylated product 15a. Oxidation of
15a provided diol 16a, which will be converted into 17, a
key intermediate of 18. In addition, the protocol offered
easy accesses to 2-naphthyl- and 2-tolyl-substitued ana-
logues 16b and 16c by simply changing the aryl Grignard
reagents used.
References and Notes
(1) (a) Bode, S. E.; Wolberg, M.; Müller, M. Synthesis 2006,
557. (b) Oishi, T.; Nakata, T. Synthesis 1990, 635.
(c) Schneider, C. Angew. Chem. Int. Ed. 1998, 37, 1375.
(d) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev.
1993, 93, 1307. (e) Hoffmann, R. W. Angew. Chem. Int. Ed.
2000, 39, 2054. (f) Rychnovsky, R. D. Chem. Rev. 1995, 95,
2021. (g) Norcross, R. D.; Paterson, I. Chem. Rev. 1995, 95,
2041.
(2) (a) Bols, M.; Skrydstrup, T. Chem. Rev. 1995, 95, 1253.
(b) Gauthier, D. R. Jr.; Zandi, K. S.; Shea, K. J. Tetrahedron
1998, 54, 2289. (c) Fensterbank, L.; Malacria, M.; Sieburth,
S. M. Synthesis 1997, 813.
(3) Ohmiya, H.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc.
2006, 128, 1886.
(4) (a) Tamao, K.; Nakajima, T.; Kumada, M. Organometallics
1984, 3, 1655. (b) Fleming, I.; Henning, R.; Plaut, H. J.
Chem. Soc., Chem. Commun. 1984, 29.
We reported cobalt-catalyzed intramolecular Heck-type
reaction of 6-halo-1-hexene derivatives.7,8 We next turned
our attention to the Heck-type reaction of the silicon-teth-
ered substrates. Trimethylsilylmethylmagnesium chloride
(2.0 mmol, 1.7 M THF solution) was added to a mixture
of cobalt(II) chloride (0.05 mmol) and 1,4-bis(diphen-
ylphosphino)butane (0.06 mmol) in THF. The resulting
mixture was stirred for 5 minutes, and substrate 2 (0.5
mmol) was added at 0 °C. The mixture was heated at re-
flux for 10 minutes, usual work-up followed by silica gel
column purification afforded the alcohol 19 in 65% yield
(Scheme 6). In this process, the Heck-type reaction of-
fered methyleneoxasilacyclopentane 18, which was then
alkylated with trimethylsilylmethyl Grignard reagent,
yielding 19. This Heck-type reaction was applicable to the
primary iodide 8a to yield 21. We attempted the synthesis
of b-hydroxyketone. However, Tamao–Fleming oxida-
tion of 19 and 21 resulted in failure.
(5) Bajwa, J. S.; Anderson, R. C. Tetrahedron Lett. 1991, 32,
3021.
(6) (a) Shen, D.-M.; Shu, M.; Mills, S. G.; Chapman, K. T.;
Malkowitz, L.; Springer, M. S.; Gould, S. L.; DeMartino, J.
A.; Siciliano, S. J.; Kwei, G. Y.; Carella, A.; Carver, G.;
Holmes, K.; Schleif, W. A.; Danzeisen, R.; Hazuda, D.;
Kessler, J.; Lineberger, J.; Miller, M. D.; Emini, E. A.
Bioorg. Med. Chem. Lett. 2004, 14, 935. (b) Conlon, D. A.;
Jensen, M. S.; Palucki, M.; Yasuda, N.; Um, J. M.; Yang, C.;
Hartner, F. W.; Tsay, F.; Hsiao, Y.; Pye, P.; Rivera, N. R.;
Hughes, D. L. Chirality 2005, 17, S149.
(7) (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn.
1971, 44, 581. (b) Heck, R. F.; Nolley, J. P. Jr. J. Org. Chem.
1972, 37, 2320.
CoCl2 (10 mol%)
Me
(8) (a) Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K. J.
Am. Chem. Soc. 2002, 124, 6514. (b) Fujioka, T.;
Nakamura, T.; Yorimitsu, H.; Oshima, K. Org. Lett. 2002, 4,
2257. (c) Affo, W.; Ohmiya, H.; Fujioka, T.; Ikeda, Y.;
Nakamura, T.; Yorimitsu, H.; Oshima, K.; Imamura, Y.;
Mizuta, T.; Miyoshi, K. J. Am. Chem. Soc. 2006, 128, 8068.
(9) General Procedure for Sequential Cyclization–Cross-
Coupling Reaction.
O
O
DPPB (12 mol%)
Me
Me
Me
Si
Si
Me3SiCH2MgCl (2.0 mmol)
I
THF, reflux, 10 min
Me3SiCH2MgCl
18
2 (0.5 mmol)
OH
Me Me
Si
SiMe3
Anhyd CoCl2 (3.2 mg, 0.025 mmol) was placed in a 20-mL
reaction flask and was heated with a hair dryer in vacuo for
2 min. After the color of the cobalt salt became blue, anhyd
THF (2 mL) and racemic 1 (20 mg, 0.12 mmol) were
sequentially added under argon. The mixture was stirred for
3 min and 6-halo-4-oxa-3-sila-1-hexene derivative 2 (155
mg, 0.5 mmol) was added. Phenylmagnesium bromide (1.0
M THF solution, 0.75 mL, 0.75 mmol) was then added over
5 s to the reaction mixture at 25 °C. While the Grignard
reagent was being added, the mixture turned brown. After
being stirred for 15 min at 25 °C, the reaction mixture was
poured into sat. NH4Cl solution. The products were
extracted with hexane (2 × 20 mL). The combined organic
layer was dried over Na2SO4 and concentrated to provide a
yellow oil. The 1H NMR analysis with dibromomethane as
an internal standard indicated the formation of the desired
oxasilacyclopentane 3a in 93% yield. Then, KF (58 mg, 1.0
mmol) and KHCO3 (100 mg, 1.0 mmol) were dissolved in
MeOH–THF (5 mL, 1:1 mixture). The crude product and
30% aq H2O2 (0.52 mL) were successively added. After
being stirred at r.t. for 12 h, the reaction mixture was poured
into sat. Na2S2O3 solution. The product was extracted with
EtOAc (2 × 20 mL). The combined organic layer was dried
over Na2SO4 and concentrated. Purification by silica gel
column chromatography (hexane–EtOAc = 2:1) provided
the diol 4a (81 mg, 0.37 mmol) in 74% isolated yield.
Diol 4a (1:1 mixture of diastereomers): white solid; mp 69–
19 65%
Hex
OH
Me Me
Hex
Me
Me
O
Hex
I
O
Me
Me
Si
Si
Si
SiMe3
21 63%
20
8a
Scheme 6
In summary, we have developed an access to a variery of
4-aryl-1,3-diols by a combination of the silicon-tethered
strategy and the cobalt-catalyzed radical arylative cycliza-
tion reaction. The silicon-tethered substrates also enjoyed
intramolecular Heck-type reaction upon treatment with
trimethylsilylmethylmagnesium chloride under cobalt ca-
talysis.9
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and Tech-
nology, Government of Japan.
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3064
H. Someya et al.
LETTER
72 °C. IR (nujol): 3345, 2924, 973, 743 cm–1. 1H NMR (300
MHz, CDCl3): d = 1.21–1.32 (m, 1 H), 1.32–1.52 (m, 3.5 H),
1.56–1.87 (m, 4.5 H), 2.23–2.29 (br s, 2 H), 2.71–2.94 (m, 2
H), 3.86 (m, 0.5 H), 4.04–4.08 (m, 1 H), 4.40 (m, 0.5 H),
7.20–7.35 (m, 5 H). 13C NMR (125.7 MHz, CDCl3): d =
18.63, 19.97, 20.35, 25.00, 25.83, 25.88, 33.23, 33.87,
41.38, 41.97, 44.23, 44.77, 67.40, 72.43, 76.59, 77.62,
126.66, 126.75, 128.82, 128.88, 129.44, 129.50, 138.82,
138.83.
A Typical Procedure for Heck-Type Reaction.
The CoCl2 (6.5 mg, 0.05 mmol) was placed in a 20-mL
reaction flask and was heated with a hair dryer in vacuo for
2 min. Then, DPPB (26 mg, 0.06 mmol) and anhyd THF (0.1
mL) were added under argon. After the mixture being stirred
for about 5 min at r.t., trimethylsilylmethylmagnesium
chloride (1.7 M THF solution, 1.2 mL, 2.0 mmol) and 2 (155
mg, 0.5 mmol) were sequentially added dropwise to the
reaction mixture at 0 °C. The resulting mixture was heated at
reflux for 10 min. After the mixture was cooled to r.t., the
reaction mixture was poured into sat. NH4Cl solution. The
products were extracted with EtOAc (2 × 20 mL). The
combined organic layer was dried and concentrated in
vacuo. Chromatographic purification on silica gel afforded
the alcohol 19 (87 mg, 0.32 mmol) in 65% isolated yield.
Alcohol 19: oil. IR (neat): 3567, 1447, 1249, 1051, 837 cm–1.
1H NMR (300 MHz, C6D6): d = –0.24 (s, 2 H), 0.05 (s, 9 H),
0.11 (s, 3 H), 0.12 (s, 3 H), 1.16–1.42 (m, 6 H), 1.74–1.95
(m, 2 H), 2.08 (m, 1 H), 2.37 (dm, J = 12.3 Hz, 1 H), 3.86
(m, 1 H), 5.45 (d, J = 2.7 Hz, 1 H), 5.64 (dd, J = 2.7, 1.2 Hz,
1 H). 13C NMR (125.7 MHz, C6D6): d = 0.22, 0.48, 1.87,
2.86, 20.40, 24.98, 27.11, 33.18, 47.22, 66.98, 125.68,
156.10. Anal. Calcd for C14H30Si2O: C, 62.15; H, 11.18.
Found: C, 62.39; H, 11.44.
Synlett 2006, No. 18, 3061–3064 © Thieme Stuttgart · New York