LETTER
Allylic Substitution and Utilization of anti SN2′ Products
1153
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tion. TBDPS protection of 14 was followed by reduction
with DIBAL-H to afford alcohol 15, which was converted
into mesylate 16 in good yield. The mesyloxy group in 16
was removed with LiAlH4 and deprotection of the silyl
group with TBAF afforded 17 in high yield. The 1H NMR
was consistent with that reported,12f and the 13C-APT sup-
ports the structure.
Additionally, coupling reactions of 3a were examined to
elucidate the reactivity (Scheme 6). Sonogashira coupling
with phenylacetylene (18) proceeded at high temperatures
to afford 19 in 57% yield.2n On the other hand, an attempt-
ed Suzuki coupling with (Sia)2BCH=CHC3H6Ph with
Pd(PPh3)4 (10 mol%) in THF and 2 M NaOH (10 equiv)
(THF–H2O = 4:1) were unsuccessful, giving a mixture of
products consisting of (CH=CHC3H6Ph)2, which was con-
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1
firmed by H NMR analysis. Fortunately, the coupling
was driven by the use of the alkenyltrifluoroborate 20, fur-
nishing 21 in 80% yield.15 Nitrile 22 was synthesized by
reaction with CuCN at high temperatures in 82% yield.
Ph
H
18
Ph
(1.3 equiv)
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J. Chem. Soc., Perkin Trans. 1 2000, 1807.
Pd(PPh3)4 (5 mol%), CuI (10 mol%)
3aa
piperidine (2 equiv), dioxane–H2O, reflux
57%
Ph
19
Bu
20
KF3B
Bu
(1.5 equiv)
3ab
Pd(PPh3)2Cl2 (10 mol%)
Cs2CO3 (5 equiv)
THF–H2O (10:1), 70–75 °C
80%
Ph
21
22
CN
Ph
CuCN (1.2 equiv)
3ab
NMP, 160–170 ºC
82%
(4) (a) Calaza, M. I.; Hupe, E.; Knochel, P. Org. Lett. 2003, 5,
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a
b
Scheme 6 Coupling reactions of 3a. 86% ee. Racemic bromide
was used.
(5) (a) Feng, C.; Kobayashi, Y. J. Org. Chem. 2013, 78, 3755.
(b) Wang, Q.; Kobayashi, Y. Org. Lett. 2011, 13, 6252.
(c) Kaneko, Y.; Kiyotsuka, Y.; Acharya, H. P.; Kobayashi,
Y. Chem. Commun. 2010, 46, 5482. (d) Kiyotsuka, Y.;
Kobayashi, Y. J. Org. Chem. 2009, 74, 7489. (e) Hyodo, T.;
Kiyotsuka, Y.; Kobayashi, Y. Org. Lett. 2009, 11, 1103.
(f) Kiyotsuka, Y.; Katayama, Y.; Acharya, H. P.; Hyodo, T.;
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Org. Lett. 2008, 10, 1719.
In summary, allylic substitution of the 2-bromocyclohex-
2-enyl phosphate with ArCu·MgBr2 afforded the anti SN2′
products in good yields and with sufficient chirality trans-
fer. The reaction scope was examined with nine re-
agents.16
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, and Culture, Ja-
pan.
(6) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
(7) Berti, G.; Macchia, B.; Macchia, F.; Monti, L. J. Org. Chem.
1968, 33, 4045.
(8) Compound 10a in the literature7 was converted into the
known (S)-2-phenyladipic acid for elucidation of the
absolute configuration.
Supporting Information for this article is available online at
m
iotSrat
ungIifoop
r
t
(9) Additionally, our designation of the R configuration to 6
correlated the R configuration with the dextrorotatory (+)
property: [α]D20 +107 (c 0.33, CHCl3) for 74% ee of 6.
However, the S configuration was assigned to the same
dextrorotatory 6 {[α]D22 +140.8 (c 1.02, CHCl3) for 96% ee}
in the literature10 probably by speculation.
References and Notes
(1) (a) Holub, N.; Neidhöfer, J.; Blechert, S. Org. Lett. 2005, 7,
1227. (b) Nicolaou, K. C.; Ding, H.; Richard, J.-A.; Chen, D.
Y.-K. J. Am. Chem. Soc. 2010, 132, 3815.
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Synlett 2014, 25, 1150–1154