Realization of anti-SN2′ selective allylation of 4-cyclopentene-1,3-diol monoester with aryl- and alkenyl-zinc reagents

Article abstract of DOI:10.1021/ol8002354

(Chemical Equation Presented) Anti-S_N2′ mode of allylation of the monoester of 4-cyclopentene-1,3-diol with aryl and alkenyl anions was achieved, for the first time, with the MeOCH₂CO₂- group as a leaving group to which R-ZnBr and CuCl (as a catalyst) were best fitted. The aryl groups successfully installed were Ph, o- and p-MeC₆H ₄, o-MOMOC₆H₄, o-MeOC₆H₄, and p-F-C₆H₄, while cis and trans alkenyl groups were attached with retention of the olefinic stereochemistries.

Full text of DOI:10.1021/ol8002354

ORGANIC
LETTERS
2
008
Vol. 10, No. 7
345-1348
Realization of Anti-SN2′ Selective
1
Allylation of 4-Cyclopentene-1,3-diol
Monoester with Aryl- and Alkenyl-Zinc
Reagents
†
†
‡
,†
Kenya Nakata, Yohei Kiyotsuka, Tomoya Kitazume, and Yuichi Kobayashi*
Department of Biomolecular Engineering, Tokyo Institute of Technology, Box B52,
Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan, and Department of
Bioengineering, Tokyo Institute of Technology, Box B44, Nagatsuta-cho 4259,
Midori-ku, Yokohama 226-8501, Japan
ykobayas@bio.titech.ac.jp
Received December 11, 2007
ABSTRACT
Anti-S
MeOCH
Ph, o- and p-MeC
stereochemistries.
N
2
′
mode of allylation of the monoester of 4-cyclopentene-1,3-diol with aryl and alkenyl anions was achieved, for the first time, with the
CO group as a leaving group to which R-ZnBr and CuCl (as a catalyst) were best fitted. The aryl groups successfully installed were
, o-MOMOC , o-MeOC , and p-F , while cis and trans alkenyl groups were attached with retention of the olefinic
2
2
−
H
6 4
H
6 4
H
6 4
6 4
−C H
The title monoester 1 is the complementary starting material
to the well-established cyclopentenones in organic synthesis.
reactivity and the selectivity with hard carbon nucleophiles
are dependent on the type of reagents and the conditions.
The nickel-catalyzed reaction of 1A with aryl and alkenyl
1
For installation of a side chain on it, allylic substitution is a
convenient reaction in regard to accessibility of various types
borates takes place regioselectively at R site with inversion
2
5
of reagents, though the regio- and stereochemistries should
of configuration (S
N
2 type), while the palladium-catalyzed
be highly controlled. So far, this type of allylic substitution
has partially been successful with certain types of reagents.
In brief, the palladium-catalyzed allylation of monoacetate
reaction with alkyl and aryl Grignard reagents does at γ site
with retention (syn-S 2′ type) though the regioselectivity
N
6
(3) (a) Montforts, F.-P.; Gesing-Zibulak, I.; Grammenos, W.; Schneider,
1
A with soft carbon nucleophiles proceeds efficiently at R
M.; Laumen, K. HelV. Chim. Acta 1989, 72, 1852-1859. (b) Deardorff, D.
R.; Linde II, R. G.; Martin, A. M.; Shulman, M. J. J. Org. Chem. 1989, 54,
3,4
carbon with retention of configuration. On the other hand,
2
759-2762. (c) Acharya, H. P.; Kobayashi, Y. Tetrahedron Lett. 2004,
†
Department of Biomolecular Engineering.
Department of Bioengineering.
45, 1199-1202. (d) Igarashi, J.; Katsukawa, M.; Wang, Y.-G.; Acharya,
H. P.; Kobayashi, Y. Tetrahedron Lett. 2004, 45, 3783-3786. (e) Acharya,
H. P.; Kobayashi, Y. Angew. Chem., Int. Ed. 2005, 44, 3481-3484.
(4) Reactions of substrates similar to 1 with soft nucleophiles: (a) Lackey,
J. W.; Mook, R. A., Jr.; Partridge, J. J. U.S. Patent US 90-505861, 1991;
Chem. Abstr. 1992, 116, 40967. (b) Trost, B. M.; Van Vranken, D. L.;
Bingel, C. J. Am. Chem. Soc. 1992, 114, 9327-9343. (c) Knight, S. D.;
Overman, L. E.; Pairaudeau, G. J. Am. Chem. Soc. 1995, 117, 5776-5788.
(5) Kobayashi, Y.; Murugesh, M. G.; Nakano, M.; Takahisa, E.; Usmani,
S. B.; Ainai, T. J. Org. Chem. 2002, 67, 7110-7123.
‡
(
1) Reviews: (a) Noyori, R.; Suzuki, M. Chemtracts-Org. Chem. 1990,
3
1
, 173-197. (b) Collins, P. W.; Djuric, S. W. Chem. ReV. 1993, 93, 1533-
564.
(
2) Reviews: (a) Kobayashi, Y. Curr. Org. Chem. 2003, 7, 133-147.
(
5
b) Helmchen, G.; Ernst, M.; Paradies, G. Pure Appl. Chem. 2004, 76, 495-
06. (c) Kar, A.; Argade, N. P. Synthesis 2005, 2995-3022. (d) Kobayashi,
Y. In Modern Organonickel Chemistry; Tamaru, Y., Ed.; Wiley-VCH:
Weinheim, 2005; pp 56-101.
1
0.1021/ol8002354 CCC: $40.75
© 2008 American Chemical Society
Published on Web 03/11/2008

Table 1. CuX-Catalyzed Reaction of 1A-D with PhZnXa
yields (%)b
entry substr.
R
reagentc
CuX
2ad
24
88 (75)
24
23
86
93
76
72
9
ester of 2a 3ad
4
anti-SN2′:SN2 convn (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1A
1B
1C
1D
1B
1B
1B
1B
1B
1B
1B
1B
1B
Me
PhZnBr‚LiBr‚n-BuBr CuCl
PhZnBr‚LiBr‚n-BuBr CuCl
PhZnBr‚LiBr‚n-BuBr CuCl
1
6
0
0
0
3
0
0
0
0
0
0
0
0
4
0
0
9
0
3
0
3
1
5
3
7
12
0
> 99:1
> 99:1
> 99:1
88:12
-e
CH2OMe
CH2Cl
100
f
f
26
0
7
4
7
97
94
2,6-Cl2C6H3 PhZnBr‚LiBr‚n-BuBr CuCl
CH2OMe
CH2OMe
CH2OMe
CH2OMe
CH2OMe
CH2OMe
CH2OMe
CH2OMe
CH2OMe
PhZnBr‚LiBr
PhZnBr‚LiBr‚n-BuI
PhZnBr‚LiBr‚n-BuBr CuBr
PhZnBr‚LiBr‚n-BuBr CuI
PhZnBr‚LiBr‚n-BuBr CuCN
PhZnBr‚LiBr‚n-BuBr (CuOTf)2‚C6H6 44
PhZnBr‚LiBr‚n-BuBr Cu(OAc)2
PhZnCl‚LiCl‚n-BuBr
PhZnI‚LiI‚n-BuBr
CuCl
CuCl
> 99:1
> 99:1
> 99:1
> 99:1
> 99:1
> 99:1
> 99:1
> 99:1
81:19
100
100
95
96
91
86
81
-
89
4
f
f
f
e
f
13
14
17
22
13
0
1
2
3
16
6
17
CuCl
CuCl
a
Reactions were carried out with “PhZnX” (3 equiv) in the presence of a copper catalyst (30 mol %) in THF/Et2O (2:1) at room temperature for 12 h.
b
1
c
Determined by H NMR spectroscopy with 1-bromonaphtalene as an internal standard. PhZnX‚LiX‚n-BuX′ were prepared from PhX′, n-BuLi, and ZnX2,
whereas PhZnBr‚LiBr was derived from PhLi (purchased from a company) and ZnBr2. Ar ) Ph. e Substrates 1A and 1B were recovered in 21 and 88%
d
yields in entries 1 and 12, respectively. f Unidentified products were also produced.
is moderate. As for copper-mediated reaction with alkyl
reagents, control at the R and γ sites with inversion (S
and anti-S 2′ type) has been successful by properly choosing
the ratio of alkyl-MgX/CuCN and the solvent among THF
discovered a reaction system consisting of methoxyacetate
1B (R ) CH OMe), aryl- and alkenylzinc bromides (abbre-
viated as sp -RZnX), and a CuCl catalyst, for the first time
N
2
2
2
N
(eq 1).
7,8
2 N
and Et O. Later, the S 2 type of the allylation was extended
9
to aryl Grignard reagents.
In contrast, application of the alkyl reagent system (RMgX/
7
CuCN) developed for the anti-S
N
2′ allylation to the phenyl
reagent of several types produced a mixture of the regio-
1
0,11
isomers.
N N
The low anti-S 2′ (high S 2) selectivity of the
aryl- and alkenyl reagents/CuX is also observed in the
literatures with other cyclopentenyl esters12 and epoxide.
13
The high anti-S
metal/CuX reagents. Nevertheless, we continued investiga-
tion to realize anti-S 2′ selective allylation, and eventually
N
N
2′ selectivity has been reported with alkyl-
14
15
(
6) Hattori, H.; Abbas, A. A.; Kobayashi, Y. Chem. Commun. 2004, 884-
85.
7) Ito, M.; Matsuumi, M.; Murugesh, M. G.; Kobayashi, Y. J. Org.
Chem. 2001, 66, 5881-5889.
8) Applications: (a) Ainai, T.; Matsuumi, M.; Kobayashi, Y. J. Org.
2
In general, sp -RZnX is the reagent used for the palladium-
8
(
and nickel-catalyzed cross-coupling with aryl and alkenyl
halides (known as the Negishi coupling), whereas the use
of sp -RZnX in palladium-catalyzed allylation of cyclic and
acyclic allylic esters has been reported. As for the copper-
assisted allylation with sp -RZnX, the low regioselectivity
and reactivity have been observed in the reaction with acyclic
16
(
2
Chem. 2003, 68, 7825-7832. (b) Yagi, K.; Nonaka, H.; Acharya, H. P.;
Furukawa, K.; Ainai, T.; Kobayashi, Y. Tetrahedron 2006, 62, 4933-4940.
17
(9) (a) Kobayashi, Y.; Nakata, K.; Ainai, T. Org. Lett. 2005, 7, 183-
2
1
86. (b) Nakata, K.; Kobayashi, Y. Org. Lett. 2005, 7, 1319-1322. (c)
Nonaka, H.; Wang, Y.-G.; Kobayashi, Y. Tetrahedron Lett. 2007, 48, 1745-
748.
10) Reaction of 1A in Et2O with PhMgBr/CuCN (cat), Ph2Cu(CN)-
1
(
(
MgBr)2, and PhCu(CN)(MgBr) gave 3a (SN2 product) in 10-60% yields
(14) (a) Curran, D. P.; Chen, M.-H.; Leszczweski, D.; Elliott, R. L.;
Rakiewicz, D. M. J. Org. Chem. 1986, 51, 1612-1614. (b) Ernst, M.;
Helmchen, G. Angew. Chem., Int. Ed. 2002, 41, 4054-4056. (c) Calaza,
M. I.; Hupe, E.; Knochel, P. Org. Lett. 2003, 5, 1059-1061. (d) Menard,
F.; Chapman, T. M.; Dockendorff, C.; Lautens, M. Org. Lett. 2006, 8, 4569-
4572. (e) Soorukram, D.; Knochel, P. Org. Lett. 2007, 9, 1021-1023.
(15) CuCl-catalyzed reactions of 1A with PhMgBr and PhZnBr (from
PhMgBr and ZnBr2) both in THF and in Et2O at room temperature for 12
h afforded a mixture of 2a and 3a in 39:61 and 64:36 ratios, respectively.
Reaction with Ph2Cu(CN)Li2 (from PhLi and CuCN) in THF produced a
34:66 mixture. Knochel reagents derived from Ph2Zn (from PhLi and ZnBr2)
and CuCN‚2LiCl in 2:1 and 1:1 ratios in THF afforded a mixture of 2a
and 3a with 54:46 and 77:23 ratios, respectively.
with 70-60% regioselectivity, whereas that with PhCu(CN)(MgCl) and
PhCu(CN)(MgBr) in THF afforded 2a (anti-SN2′ product) in ca. 20% yields
with ca. 70% regioselectivity.
(11) Low to moderate selectivities reported for allylation with aryl- and
alkenyl-MgX/CuX: (a) Tseng, C. C.; Paisley, S. D.; Goering, H. L. J. Org.
Chem. 1986, 51, 2884-2891. (b) Torneiro, M.; Fall, Y.; Castedo, L.;
Mouri n˜ o, A. J. Org. Chem. 1997, 62, 6344-6352. (c) Borthwick, S.; Dohle,
W.; Hirst, P. R.; Booker-Milburn, K. I. Tetrahedron Lett. 2006, 47, 7205-
7
208.
12) (a) Corey, E. J.; Mann, J. J. Am. Chem. Soc. 1973, 95, 6832-6833.
b) Finch, M. A. W.; Lee, T. V.; Roberts, S. M. J. Chem. Soc., Chem.
Commun. 1979, 677-678. (c) Mori, S.; Takechi, S. Heterocycles 1990,
1, 1195-1199. (d) Piarulli, U.; Daubos, P.; Claverie, C.; Roux, M.;
Gennari, C. Angew. Chem., Int. Ed. 2003, 42, 234-236.
13) Marino, J. P.; Fern a´ ndez de la Pradilla, R.; Laborde, E. J. Org. Chem.
987, 52, 4898-4913.
(
(
3
(16) (a) Negishi, E.; Liu, F. In Metal-Catalyzed Cross-Coupling Reac-
tions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998;
Chapter 1. (b) Negishi, E. Handbook of Organopalladium Chemistry for
Organic Synthesis, Vol. 1; Wiley-VCH: Weinheim, 2002.
(
1
1346
Org. Lett., Vol. 10, No. 7, 2008

substrates18 except for one cyclic case,19 whereas high anti-
2
b,14b,19,20
N
S 2′ selectivity has been reported with alkyl-ZnX/CuX.
2
Table 2. CuCl-Catalyzed Reaction of 1B (R ) CH OMe) with
2
Recently, (sp -R)
2
Zn was disclosed as the anti-S
N
2′ selective
Various Organozinc Bromidesa
reagent in allylation with acyclic esters.21
The present investigation was initiated with a finding that
reaction of allylic acetate 1A (R ) Me) with PhZnBr‚LiBr‚
2
2
n-BuBr (3 equiv), prepared from PhBr, n-BuLi, and ZnBr
in the presence of 30 mol % of CuCl at room temperature
produced anti-S 2′ product 2a (Ar ) Ph) with high regio-
2
,
N
1
selectivity of >99% by H NMR analysis, but only in 24%
yield (Table 1, entry 1). Because the reaction proceeded
incompletely, other leaving groups (RCO ) with electron-
2
withdrawing moieties in R were examined (entries 2-4). The
best result was obtained with methoxyacetate 1B to produce
2a in high yield (75% isolated yield) with >99% regiose-
lectivity (entry 2), whereas 1C and 1D afforded a mixture
of products including 2a in low yields (entries 3 and 4). We
also examined reaction of 1B with other “PhZnBr” prepared
in different ways (PhLi + ZnBr
2
2
and PhI + n-BuLi + ZnBr )
to expand reagent sources (entries 5 and 6 vs entry 2). A
similar result observed with PhZnBr‚LiBr22 (entry 5) indi-
cates no consumption of PhZnBr by perhaps conceivable
copper-catalyzed coupling with n-BuBr that was coproduced
with PhLi through the PhBr/n-BuLi exchange (entry 2). To
our surprise, even n-BuI did not interfere the reaction nor
produce any byproduct (entry 6). Examination of the reagent
quantity revealed that 3 equiv is the minimum requirement
for the high efficiency. Next, catalytic activity of copper salts
a
Reactions were carried out with organozinc bromides (4 equiv) derived
from chemicals indicated in “reagent sources” in the presence of CuCl (30
b
mol %) in THF/Et O (2:1) at room temperature for 12 h. Determined by
2
1
H NMR spectroscopy with 1-bromonaphtalene as an internal standard.
c
Isolated yields are shown in parentheses. d Methoxyacetate of 2. H NMR
e 1
f
1
spectra of 3 for comparison, see refs 5 and 9. 2e/ester ) 10:1 by H NMR
spectroscopy.
A zinc reagent 6 prepared by ortho lithiation23 of meth-
oxymethyl phenyl ether (5) followed by transmetallation with
ZnBr also furnished anti-S 2′ product 2h with >99:1
2 N
other than CuCl and reactivity of reagents derived from ZnX
2
(
(
X ) Cl, I) were investigated. Among the copper salts used
entries 7-11), CuBr and CuI showed slightly lower effi-
regioselectivity in 73% isolated yield (Scheme 1).
ciency in yield and in conversion. On the other hand, the
reagents derived with ZnX (X ) Cl, I) were inferior than
-based reagent (entries 12 and 13 vs entries 2, 5,
2
the ZnBr
and 6).
2
Scheme 1. Synthesis of 2h
The procedure optimized above was applied to substi-
tuted phenyl zinc bromides to afford the anti-S 2′ products
b-e efficiently (Table 2, entries 1-4). Sterically con-
gested reagents could be participants in the reaction (entries
and 3).
N
2
2
(
17) (a) Matsushita, H.; Negishi, E. J. Chem. Soc., Chem. Commun. 1982,
1
2
6
2
1
1
60-161. (b) Dunkerton, L. V.; Serino, A. J. J. Org. Chem. 1982, 47, 2812-
814. (c) Keinan, E.; Sahai, M. J. Chem. Soc., Chem. Commun. 1984, 648-
50. (d) Fiaud, J.-C.; Aribi-Zouioueche, L. J. Organometal. Chem. 1985,
95, 383-387. (e) Hayashi, T.; Yamanoto, A.; Hagihara, T. J. Org. Chem.
986, 51, 723-727. (f) Fiaud, J.-C.; Legros, J.-Y. J. Org. Chem. 1987, 52,
907-1911.
(
18) Ibuka, T.; Nakai, K.; Habashita, H.; Bessho, K.; Fujii, N. Tetra-
hedron 1993, 49, 9479-9488.
19) 2-Iodo-cycloalkenyl esters: Soorukram, D.; Knochel, P. Angew.
Chem., Int. Ed. 2006, 45, 3686-3689.
20) (a) Nakamura, E.; Sekiya, K.; Arai, M.; Aoki, S. J. Am. Chem. Soc.
989, 111, 3091-3093. (b) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J.
The present reaction was successfully extended to alkenyl
zinc reagents. As summarized in entries 5 and 6 of Table 2,
the zinc reagents prepared from the cis and trans iodides by
halogen-lithium exchange with t-BuLi followed by trans-
(
(
1
Org. Chem. 1991, 56, 1445-1453. (c) Yamamoto, Y.; Chounan, Y.; Tanaka,
M.; Ibuka, T. J. Org. Chem. 1992, 57, 1024-1026. (d) Fujii, N.; Nakai,
K.; Habashita, H.; Yoshizawa, H.; Ibuka, T.; Garrido, F.; Mann, A.;
Chounan, Y.; Yamamoto, Y. Tetrahedron Lett. 1993, 34, 4227-4230.
2 N
metallation with ZnBr produced the anti-S 2′ products 2f
and 2g in good yields without isomerization of the double
1
bond. The anti-S
analysis. The alkenyl zinc reagent derived from stannane 7
also furnished anti-S 2′ product 2i in 55% isolated yield with
99% regioselectivity (Scheme 2). Compounds similar to
N N
2′/S 2 selectivity was >99:1 by H NMR
(
21) (a) Harrington-Frost, N.; Leuser, H.; Calaza, M. I.; Kneisel, F. F.;
Knochel, P. Org. Lett. 2003, 5, 2111-2114. (b) Perrone, S.; Knochel, P.
Org. Lett. 2007, 9, 1041-1044.
N
(22) The phenylzinc reagents derived from PhX, n-BuLi, and ZnX2 and
>
from pure PhLi from ZnX2 are drawn as PhZnX‚LiX‚n-BuBr and PhZnX‚
LiX, respectively. Other organometallic reagents used herein are indicated
in a similar way.
(23) Snieckus, V. Chem. ReV. 1990, 90, 879-933.
Org. Lett., Vol. 10, No. 7, 2008
1347

25
manner with almost complete regioselectivity. Application
of the present method to the synthesis of biologically
important molecules is now in progress.
Scheme 2. Synthesis of 2i
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Science, Sports, and Culture, Japan. We thank Ms. M.
Ishikawa of Center for Advanced Materials Analysis, Tech-
nical Department, Tokyo Institute of Technology, for HRMS
analysis.
Supporting Information Available: Experimental pro-
cedures and spectral data of compounds described herein.
This material is available free of charge via the Internet at
http://pubs.acs.org.
2
i were synthesized previously as prostaglandin intermediates
24
with low to moderate yields.
Finally, we applied the above reaction system to an alkyl
reagent. As shown in eq 2, n-BuZnBr‚LiBr, selected as a
typical reagent of alkyl zinc bromides, proceeded with high
OL8002354
(
24) (a) Stork, G.; Isobe, M. J. Am. Chem. Soc. 1975, 97, 4745-4746.
regioselectivity to afford anti-S
N
2′ product 8 in 82% yield.
(b) Bradbury, R. H.; Walker, K. A. M. J. Org. Chem. 1983, 48, 1741-
1750. (c) Donaldson, R. E.; Saddler, J. C.; Byrn, S.; McKenzie, A. T.; Fuchs,
P. L. J. Org. Chem. 1983, 48, 2167-2188.
(25) Typical procedure: to an ice-cold solution of PhBr (0.126 mL, 1.20
mmol) in Et2O (1.0 mL) was added n-BuLi (0.69 mL, 1.75 M in hexane,
3
No difference in regioselectivity and reactivity between sp -C
2
(
alkyl) and sp -C (aryl, alkenyl) reagents were thus estab-
lished.
1.20 mmol). After 30 min, a solution of ZnBr2 (2.70 mL, 0.45 M in THF,
1.21 mmol) was added. The solution was stirred at 0 °C for 30 min, and
CuCl (9 mg, 0.09 mmol) was added to it. After 20 min, a solution of
methoxyacetate 1B (52 mg, 0.30 mmol) in THF (1 mL) was added. The
solution was stirred at room temperature for 12 h and diluted with saturated
NH4Cl with vigorous stirring. The resulting mixture was extracted with
EtOAc four times. The combined extracts were dried over MgSO4 and
concentrated. The residue was purified by chromatography on silica gel
(
hexane/EtOAc ) 4:1) to furnish 2a (36 mg, 75%). The spectral data were
identical with those reported: (a) Echavarren, A. M.; Tueting, D. R.; Stille,
J. K. J. Am. Chem. Soc. 1988, 110, 4039-4041. (b) Tueting, D. R.;
Echavarren, A. M.; Stille, J. K. Tetrahedron 1989, 45, 979-992.
In conclusion, we have presented a new reagent system
for delivering aryl, alkenyl, and alkyl groups in an anti-S 2′
N
1348
Org. Lett., Vol. 10, No. 7, 2008