Stille cross-coupling reactions using vinylcyclopropylstannanes

Article abstract of DOI:10.1055/s-0029-1217327

The Stille cross-coupling reaction between a vinylcyclopropylstannane and iodobenzene or phenol triflate provides an expedious route to 1,2-phenylvinylcyclopropanes. However, similar coupling reactions using ortho-substituted aromatic substrates also lead

Full text of DOI:10.1055/s-0029-1217327

1800
LETTER
Stille Cross-Coupling Reactions Using Vinylcyclopropylstannanes
Stille
C
ross-Coupl
e
ing
R
eactio
r
ns
U
sing
a
V
inylcycl
l
opropy
d
lstannanes Pattenden,* Davey A. Stoker
School of Chemistry, The University of Nottingham, Nottingham, NG7 2RD, UK
Fax +44(115)9513535; E-mail: gp@nottingham.ac.uk
Received 3 February 2009
tween 6 and diiodomethane in the presence of diethylzinc
at –50 °C next gave the cyclopropane methanol 7a (74%).
Oxidation of 7a to the corresponding aldehyde 7b, using
IBX and DMSO, followed by a straightforward Wittig
Abstract: The Stille cross-coupling reaction between a vinylcyclo-
propylstannane and iodobenzene or phenol triflate provides an ex-
pedious route to 1,2-phenylvinylcyclopropanes. However, similar
coupling reactions using ortho-substituted aromatic substrates also
lead to butylaromatic products, resulting from competitive sp3–sp2 reaction with methyltriphenylphosphoranylid then gave
the trans-vinylcyclopropylstannane 3.6
coupling reactions.
Key words: Stille reaction, cross-coupling, arylations, vinyl cyclo-
propanes, sp3–sp2 coupling
i
OH
Bu3Sn
OH
6
ii
iv
R
Palladium-catalysed cross-coupling reactions involving a
wide variety of saturated and unsaturated organostannane
precursors are ubiquitous in organic synthesis.1 In connec-
tion with a specific synthetic objective, that is, the synthe-
sis of 1,2-arylvinyl-substituted cyclopropanes 1, it came
as a surprise to us therefore that the Stille coupling reac-
tion between vinylcyclopropylstannanes, for example, 3
and aryl derivatives 2 (Scheme 1), had not been de-
scribed.2–4 We surmise that the absence of such a descrip-
tion in the literature may have its origins in the propensity
for vinylcyclopropanes to undergo Pd(II)-catalysed ring-
opening reactions, and/or for the arylvinylcyclopropane
products to undergo 6p-electrocyclisation in situ, leading,
in both cases, to cyclic byproducts, namely 4 and 5, re-
spectively. We have therefore evaluated the scope for
cross-coupling reactions involving the vinylcyclopropyl-
stannane 3 and a series of substituted aryl triflate and ha-
lides. Here we present the outcome of this study and draw
attention to an interesting dichotomous reaction pathway
followed by the stannane 3.
3
Bu3Sn
iii
7
a, R = CH2OH
b, R = CHO
OTf
X
Bu
X
v, 3
+
X
8
9
10
a, X = OH
b, X = (E)-CH=CHCO2Et
c, X = (E)-CH2CH=C(Me)(CH2)2CO2Et
d, X = CH2CH=CH2
Scheme 2 Reagents and conditions: i, Bu3SnH, AIBN, 100 °C, 5 h,
89%; ii, CH2I2, Et2Zn, CH2Cl2, –50 °C, 74%; iii, IBX, DMSO, 25 °C,
20 h, 96%; iv, MePPh3Br, NaHMDS, –78 °C, 97%; v, Pd(OAc)2,
Ph3As, CuI, LiCl, NMP, 24 h, 40–70%, ratios of 9/10 = ~ 1:2.
After examining a range of reaction conditions and cata-
lytic systems, we found that when a solution of the vinyl-
cyclopropylstannane 3 and phenoltriflate in NMP was
added to palladium acetate (10 mol%) which had been
premixed with triphenylarsine (60 mol%), and the result-
ing mixture was stirred and heated at 80 °C for 24 hours
in the presence of CuI (20 mol%) and LiCl (6 equiv), a
reproducible 70% yield of the phenylvinylcyclopropane 1
(R = H) could be realised. A similar outcome was seen
using iodobenzene in place of phenoltriflate.7 What came
as a surprise to us was that when we examined the cross-
coupling reactions between 3 and the phenoltriflates 8,
substituted at their ortho positions with oxy and carbon
groups, we obtained the corresponding n-butylaromatic
compounds 10 as major products.
The trans-vinylcyclopropylstannane 3 was easily accessi-
ble from propargyl alcohol using four straightforward
steps (Scheme 2). Thus, treatment of propargyl alcohol
with Bu3SnH–AIBN first led to the known (E)-vinylstan-
nane 6 in 89% yield.5 A Simmons–Smith reaction be-
OTf
Pd(0)
+
Bu3Sn
R
R
1
2
3
R
R
Thus, a palladium-catalysed coupling reaction between
the vinylcyclopropylstannane 3 and catechol monotriflate
(8a) led to a 2:1 mixture of o-butylphenol (10a) and the
phenolvinylcyclopropane (9a). Likewise, separate similar
coupling reactions between 3 and the ortho-substituted
triflates 8b, 8c, and 8d gave approximately 2:1 mixtures
4
5
Scheme 1
SYNLETT 2009, No. 11, pp 1800–1802
x
x
.x
x
.2
0
0
9
Advanced online publication: 02.06.2009
DOI: 10.1055/s-0029-1217327; Art ID: D04109ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Stille Cross-Coupling Reactions Using Vinylcyclopropylstannanes
1801
(7) Typical Stille Coupling Procedure: Pd(OAc)2 (10 mol%),
Ph3As (60 mol%), CuI (20 mol%), and LiCl (6 equiv) were
dissolved in NMP, and the mixture was then stirred at r.t.
under an argon atmosphere for 10 min. A soln of the
aryltriflate or aryliodide (1.0 equiv.) and the stannane3 (1.05
equiv) in NMP was added dropwise over 1 min, and the
mixture was then degassed and heated to 80 °C for 24 h. The
cooled mixture was poured onto H2O (50 mL) and EtOAc
(50 mL), and the separated aqueous extract was extracted
with EtOAc (3 × 100 mL). The combined organic extracts
were washed successively with H2O (3 × 20 mL), 2 M aq
HCl (10 mL) and brine (50 mL), then dried (Na2SO4) and
concentrated in vacuo to leave the coupled product (s) as a
colourless oil. Chromatographic separation and purification
was carried out on SiO2, using PE (bp 40–60 °C), then 1–6%
EtOAc in PE as eluant. The o-butylphenol (10a) showed
identical spectroscopic data to those reported in the
literature.10
of the corresponding substituted butylbenzenes 10b, 10c,
and 10d, and phenylvinylcyclopropanes 9b, 9c, and 9d,
respectively, in combined yields of approximately 40%.
Although deliberate sp3–sp2 cross-coupling reactions be-
tween butylstannanes and aryl iodides/triflates have been
used in synthesis,8 the preferential migration of the sp3-
butyl group within vinyl- and aryltributylstannanes in
Stille cross-coupling reactions is quite rare.9 This feature,
of course, is the main reason why the Stille sp2–sp2 cross-
coupling reaction has been so revered in synthesis! In the
specific cases of the coupling reactions involving the
vinylcyclopropylstannanes 3 and the ortho-substituted
triflates 8, the Stille reaction is clearly limited. We suggest
that this limitation is associated with steric impedance be-
tween the stannane 3 and the ortho substituents within the
arylpalladium species at the stage of triflate–cyclopropyl/
butyl exchange in the catalytic cycle, favouring butyl
group over cyclopropane ring migration.
Butylcinnamate 10b
IR (CHCl3): nmax = 1727cm–1. 1H NMR (360 MHz, CDCl3):
d = 0.94 (3 H, t, J = 7.0 Hz, CH2CH3), 1.35 (3 H, t, J = 7.0
Hz, OCH2CH3), 1.60–1.70 (4 H, m, CH2CH2), 2.75 (2 H, t,
J = 7.0 Hz, ArCH2), 4.28 (2 H, t, J = 7.0 Hz, OCH2CH3), 6.40
(1 H, d, J = 15.0 Hz, COCH=), 7.10–7.70 (4 H, m, ArH),
8.04 (1 H, d, J = 15.0 Hz, ArCH=) ppm. 13C NMR (90 MHz,
CDCl3): d = 13.9 (CH3), 14.3 (CH3), 22.5 (CH2), 25.6 (CH2),
33.8 (CH2), 60.5 (CH2), 119.3 (CH), 126.5 (CH), 127.3
(CH), 128.6 (CH), 130.0 (CH), 133.7 (C), 134.0 (C), 142.3
(CH), 168.0 (C) ppm.
Acknowledgment
We thank the EPSRC (Studentship to D.A.S.) and AstraZeneca for
support.
References and Notes
Butylaromatic Compound 10c
1H NMR (360 MHz, CDCl3): d = 0.96 [3 H, t, J = 7.0 Hz,
(CH2)2CH3], 1.30 (3 H, t, J = 7.5 Hz, OCH2CH3), 1.33 (2 H,
m, CH2CH2CH3), 1.62 (2 H, app. pent., J = ca. 7 Hz,
CH2CH2CH2) 1.71 (3 H, s, CH=CCH3), 2.20–2.40 (4 H, m,
CH2CH2CO2Et), 2.55 (2 H, t, J = 7.0 Hz, ArCH2), 3.22 (2 H,
d, J = 6.0 Hz, ArCH2CH=), 4.12 (2 H, q, J = 7.5 Hz,
OCH2CH3), 5.80 (1 H, t, J = 6.0 Hz, =CHCH2), 6.90–7.05 (4
H, m, ArH) ppm. 13C NMR (90 MHz, CDCl3): d = 14.1
(2 × CH3), 17.1 (CH3), 22.4 (CH2), 29.6 (CH2), 31.9 (CH2),
33.8 (CH2), 34.6 (CH2), 35.2 (CH2), 61.3 (CH2), 122.8 (CH),
125.6 (CH), 125.9 (CH), 128.1 (CH), 128.9 (CH), 135.5 (C),
136.5 (C), 136.6 (C), 173.1 (C) ppm.
(1) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
(b) Farina, V.; Krishnamurthy, V.; Scott, W. K. In Organic
Reactions, Vol. 50; Wiley: New York, 1997. (c) Mitchell,
T. N. In Metal-Catalyzed Cross-Coupling Reactions;
de Meijere, A.; Diederich, F., Eds.; Wiley-VCH: Weinheim,
2004, Chapt. 3.
(2) For a Negishi cross-coupling involving a
vinylcyclopropylstannane and a vinyl iodide, see: Piers, E.;
Jean, M.; Marrs, P. S. Tetrahedron Lett. 1987, 43, 5075.
(3) For zirconium-catalysed and Negishi cross-coupling
reactions using vinylcyclopropyl halides and vinyl
substrates, see: (a) Thomas, E.; Kasatkin, A. N.; Whitby,
R. J. Tetrahedron Lett. 2006, 52, 9181. (b) Piers, E.; Coish,
P. D. G. Synthesis 2001, 251.
(4) For some Suzuki cross-coupling reactions using cyclopropyl
boronic acids, see: (a) Baba, D.; Yang, Y.-J.; Uang, B.-J.;
Fuchigami, T. J. Fluorine Chem. 2003, 1, 93. (b) Rubina,
M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2003, 24,
7198. (c) Wallace, D. J.; Chen, C.-Y. Tetrahedron Lett.
2002, 39, 6987. (d) Zhou, S.-M.; Deng, M.-Z.; Xia, L.-J.;
Tang, M.-H. Angew. Chem. Int. Ed. 1998, 20, 2845.
(5) Oda, H.; Kobayashi, T.; Kosugi, M.; Migita, T. Tetrahedron
1995, 51, 695.
(6) The vinylcyclopropylstannane 3 was obtained as a
colourless oil. IR (CHCl3): nmax = 3083, 1631 cm–1. 1H NMR
(400 MHz, CDCl3): d = 0.11 (1 H, ddd, J = 10.5, 8.5, 5.5 Hz,
CHSnBu3), 0.70–0.76 (2 H, m, CHCH2CH), 0.81 (6 H, t, J =
8.0 Hz, SnCH2), 0.89 (9 H, t, J = 7.5 Hz, CH2CH3), 1.25–
1.36 (6 H, m, CH3CH2), 1.36–1.44 (1 H, m, CH2=CHCH),
1.44–1.56 (6 H, m, SnCH2CH2), 4.80 (1 H, dd, J = 10.0, 1.5
Hz, HHC=CH), 5.05 (1 H, dd, J = 17.0, 1.5 Hz, HHC=CH),
5.29 (1 H, ddd, J = 17.0, 10.0, 9.0 Hz, CH2=CH) ppm.
13C NMR (100 MHz, CDCl3): d = 2.6 (CH), 8.7 (CH2), 11.5
(CH2), 13.7 (CH3), 19.4 (CH), 27.3 (CH2), 29.1 (CH2), 110.5
(CH2), 144.6 (CH) ppm. MS (EI): m/z C13H25Sn [M+ – Bu]:
301.0978; 301.0986.
Arylvinylcyclopropane 9b
1H NMR (360 MHz, CDCl3): d = 1.15–1.30 (2 H, m,
CHCH2CH), 1.60 (3 H, t, J = 7.0 Hz, CH2CH3), 1.60–1.75 (1
H, m, CHCH2CH), 2.10–2.20 (1 H, m, CHCH2CH), 4.30 (2
H, q, J = 7.0 Hz, CH2CH3), 5.10 (1 H, d, J = 11.0 Hz,
CH=CHH), 5.20 (1 H, d, J = 16.0 Hz, CH=CHH), 5.70 (1 H,
ddd, J = 16.0, 11.0, 8.0 Hz, CH=CH2), 6.40 (1 H, d, J = 15.0
Hz, ArCH=CH), 7.00–7.60 (4 H, m, ArH), 8.30 (1 H, d, J =
15.0 Hz, ArCH=CH) ppm.
Vinylcyclopropane 9c
IR (CHCl3): nmax = 3011 (s), 1727 (s), 1634 (m), 1602 (w)
cm–1. 1H NMR (400 MHz, CDCl3): d = 1.05 (1 H, app dt,
J = 8.5, 5.0Hz, ArCHCHH), 1.22 (3 H, t, J = 7.0 Hz,
OCH2CH3), 1.24–1.27 (1 H, m, ArCHCHH), 1.54–1.59 (1
H, m, H2C=CHCH), 1.72 (3 H, app s, C=CCH3), 1.96 (1 H,
ddd, J = 8.5, 5.5, 5.0 Hz, ArCH), 2.36 (2 H, t, J = 7.0Hz,
O=CCH2CH2), 2.43 (2 H, t, J = 7.0 Hz, O=CCH2CH2), 3.43
(1 H, dd, J = 16.0, 7.0 Hz, ArCHH), 3.49 (1 H, dd, J = 16.0,
7.0 Hz, ArCHH), 4.10 (2 H, q, J = 7.0 Hz, OCH2CH3), 4.96
(1 H, dd, J = 10.0, 1.5 Hz, HC=CHH), 5.13 (1 H, dd, J =
17.0, 1.5 Hz, HC=CHH), 5.34 (1 H, app tq, J = 7.0, 1.5 Hz,
C=CH), 5.58 (1 H, ddd, J = 17.0, 10.0, 8.5 Hz, H2C=CH),
6.99 (1 H, dd, J = 6.0, 2.0 Hz, ArH), 7.12–7.15 (3 H, m,
3 × ArH) ppm. 13C NMR (100 MHz, CDCl3): d = 14.2
(CH3), 14.6 (CH2), 16.2 (CH3), 23.0 (CH), 25.7 (CH), 31.6
Synlett 2009, No. 11, 1800–1802 © Thieme Stuttgart · New York

1802
G. Pattenden, D. A. Stoker
LETTER
(CH2), 33.2 (CH2), 34.7 (CH2), 60.3 (CH2), 112.4 (CH2),
123.6 (CH), 125.7, 126.0, 126.1 (3 × CH), 128.4 (CH), 134.4
(C), 139.5 (C), 140.9 (C), 141.0 (CH), 173.4 (C) ppm.
MS (ES): m/z C20H26O2Na [M + Na+]: 321.1825; found:
321.1817.
(9) For examples of some competitive alkyl vs aryl couplings
involving aryltributylstannane precursors, see: (a) Yasuda,
N.; Yang, C.; Wells, K. M.; Jensen, M. S.; Hughes, D. L.
Tetrahedron Lett. 1999, 3, 427. (b) O’Neill, D. J.; Shen, L.;
Prouty, C.; Conway, B. R.; Westover, L.; Wu, J. Z.; Zhang,
H. C.; Maryanoff, B. E.; Murray, W. V.; Demarest, K. T.;
Kuo, G. H. Bioorg. Med. Chem. 2004, 12, 3167.
(8) For some examples, see: (a) Allegretti, M.; Bertini, R.;
Cesta, M. C.; Bizzarri, C.; Di Bitondo, R.; Di Cioccio, V.;
Galliera, E.; Berdini, V.; Topai, A.; Zampella, G.; Russo, V.;
Di Bello, N.; Nano, G.; Nicolini, L.; Locati, M.; Fantucci, P.;
Florio, S.; Colotta, F. J. Med. Chem. 2005, 13, 4312.
(b) Tamayo, N.; Echavarren, A. M.; Paredes, M. C.; Fariña,
F.; Noheda, P. Tetrahedron Lett. 1990, 36, 5189.
(c) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987,
18, 5478.
(c) Paintner, F. F.; Gorler, K.; Voelter, W. Synlett 2003,
522. (d) Ito, S.; Okujima, T.; Morita, N. J. Chem. Soc.,
Perkin Trans. 1 2002, 16, 1896.
(10) Ohe, K.; Yokoi, T.; Miki, K.; Nishino, F.; Uemura, S. J. Am.
Chem. Soc. 2002, 124, 526.
Synlett 2009, No. 11, 1800–1802 © Thieme Stuttgart · New York