Copper-catalyzed three-component borylstannylation of alkynes

Article abstract of DOI:10.1002/chem.201202435

Regio- and stereoselective installation of boryl and stannyl moieties into a carbon-carbon triple bond of various alkynes has been achieved based on a three-component coupling reaction by using a diboron and a tin alkoxide with the aid of a copper(II) acetate-tricyclohexylphosphine complex, giving diverse vic-borylstannylalkenes in a straightforward manner. Carbon-tin and carbon-boron bonds of the resulting borylstannylation product are successively transformed into carbon-carbon bonds by a Migita-Kosugi-Stille and a Suzuki-Miyaura coupling, leading to the formation of (Z)-tamoxifen with anti-breast cancer activity. Borylstannylation: A copper-tricyclohexylphosphine complex was found to catalyse the three-component borylstannylation of alkynes with a diboron and a tin alkoxide to afford vic-borylstannylalkenes in a regio- and stereoselective manner. Synthetic utility of the resulting borylstannylation product was demonstrated by a three-step synthesis of (Z)-tamoxifen from commercially available substrates by successive Migita-Kosugi-Stille and Suzuki-Miyaura couplings (see scheme). Copyright

Full text of DOI:10.1002/chem.201202435

FULL PAPER
DOI: 10.1002/chem.201202435
Copper-Catalyzed Three-Component Borylstannylation of Alkynes
Yuki Takemoto, Hiroto Yoshida,* and Ken Takaki[a]
Abstract: Regio- and stereoselective
installation of boryl and stannyl moie-
ties into a carbon–carbon triple bond
of various alkynes has been achieved
based on a three-component coupling
reaction by using a diboron and a tin
alkoxide with the aid of a copper(II)
plex, giving diverse vic-borylstannylal-
kenes in straightforward manner.
Carbon–tin and carbon–boron bonds of
the resulting borylstannylation product
are successively transformed into
carbon–carbon bonds by Migita–
Kosugi–Stille and Suzuki–Miyaura
coupling, leading to the formation of
(Z)-tamoxifen with anti-breast cancer
activity.
a
a
G
a
Keywords: alkynes · boron · cop-
per · tin · total synthesis
acetate–tricyclohexylphosphine
com-
Introduction
that b-borylalkenyl–copper species could also be key inter-
mediates in a new type of borylmetalation reactions by cap-
turing with metallic electrophiles.[13] Herein, we disclose that
the use of a tin alkoxide as a third component enables the
first catalytic three-component dimetallation of unsaturated
carbon linkages to occur under copper catalysis, giving di-
verse vic-borylstannylalkenes in a regio- and stereodefined
manner. Although vic-borylstannylalkenes have been previ-
ously synthesized by the palladium-catalyzed alkyne-inser-
tion reaction into a borylstannane,[4] its extreme sensitivity
to moisture and the difficulties in its preparation impair the
synthetic utility,[4c] making the present method, which uti-
lizes stable and commercially available regents, much more
convenient and practical.
Considerable attention has been directed toward the potent
and straightforward synthesis of regio- and stereodefined di-
metallated alkenes,[1] especially hetero-dimetallated alkenes
containing B, Si and Sn.[2–4] The differences in reactivity of
À
the resulting C M(M’) bonds allow chemo- and regioselec-
tive cross-coupling reactions[5] to be carried out successively,
thus, providing direct access to tri- and tetrasubstituted al-
kenes, which constitute an important class of biologically
active compounds, such as tamoxifen,[6] droloxifene[7] and
toremifene[8] [Eq. (1)]
Results and Discussion
We first carried out the reaction of diphenylacetylene (1a)
À
with bis(pinacolato)diboron (2, (pin)B B
tin methoxide (3a) at 808C in the presence of Cu
N
U
and PCy3 (Cy=cyclohexyl), which was the most effective
catalytic system in the alkyne diborylation and observed
that three-component borylstannylation took place to afford
4a in 79% yield (Table 1, entry 1). The reaction proceeded
smoothly even at room temperature (entry 2), and, further-
more, the amount of the catalyst could be reduced to
1 mol% without apparent loss of the yield (entry 3).
Although a variety of the vic-hetero-dimetallated alkenes
can be synthesized by transition-metal-catalyzed direct inser-
tion reactions of alkynes[1–4] into metal–metal (M M’)
À
bonds, the search for new synthetic approaches is still of
great importance.[9] We have recently reported efficacious
access to vic-diborylalkenes by the copper-catalyzed dibory-
lation of alkynes with a diboron in which b-borylalkenyl–
copper species serve as key intermediates.[10,11] In view of
the nucleophilicity of organocopper species,[12] we envisaged
Besides 1a, variously substituted diarylalkynes could fa-
AHCTUNGTREGcNNUN ilely participate in the borylstannylation in which almost
equal amounts of regioisomers (4 and 4’) were generated
from unsymmetrical alkynes 1c–e (Table 2, entries 1–4). In
marked contrast, the reaction of a diarylalkyne 1 f bearing
an electron-donating (MeO) and an electron-withdrawing
(CF3) group proceeded with perfect regioselectivity, and the
stannyl moiety was attached in geminal position to the 4-
methoxyphenyl moiety (entry 5). The exclusive formation of
single regioisomers 4g–l, the stannyl moieties and the aryl
[a] Y. Takemoto, Prof. Dr. H. Yoshida, Prof. Dr. K. Takaki
Department of Applied Chemistry
Graduate School of Engineering
Hiroshima University
Higashi-Hiroshima 739-8527 (Japan)
Fax : (+81)82-424-5494
E-mail: yhiroto@hiroshima-u.ac.jp
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

Table 1. Cu-catalyzed borylstannylation of diphenylacetylene (1a).[a]
The use of tributyltin tert-butoxide (3c) instead of 3a in the
reaction of 1m significantly improved the yield by inhibiting
the by-product formation, and other internal aliphatic al-
kynes 1n–p were converted into the corresponding products
4n–p by using 3c (entries 14–17). It is worth noting that the
À
propargylic C O bonds in 1o remained intact throughout
the borylstannylation (entry 16), which is in contrast to the
result obtained in the tetraborylation of 1o with 2 in which
Entry
Temperature [8C]
Time [h]
Yield [%][b]
À
the propargylic C O bonds were transformed completely
1
80
RT
RT
4
18
37
79
87
82
[10]
À
into C B bonds. In addition, the reaction was applicable
2
3[c]
to terminal alkynes 1q–s to afford products bearing the
stannyl moiety at the more substituted site (entries 18–20).
Functional-group compatibility of the borylstannylation was
appreciably high and, thus, an aryl–Br bond (entry 3), an
alkyl–Cl bond (entry 9), and a cyano group (entry 12) were
tolerated under the reaction conditions.
[a] General procedure: 1a (0.30 mmol, 1 equiv), 2 (0.39 mmol, 1.3 equiv),
3a (0.39 mmol, 1.3 equiv), Cu(OAc)2 (6.0 mmol, 2 mol%), PCy3
(0.021 mmol, 7 mol%), toluene (1.0 mL). [b] Yield of isolated 4a. [c] Cu-
ACHTUNGTRENNUNG(OAc)2 (1 mol%) and PCy3 (3.5 mol%) were used.
AHCTUNGTRENNUNG
Similar to the copper-catalyzed diborylation,[10]
the b-borylalkenyl–copper species 7, which is gener-
ated by the addition of the borylcopper species 6 to
an alkyne, would be a key intermediate of the bor-
ylstannylation (step A, Scheme 1). Subsequent cap-
turing of 7 with a tributyltin alkoxide provides a
borylstannylated product and a copper alkoxide
Table 2. Cu-catalyzed borylstannylation of alkynes.[a]
(step B), which is transformed into 6 upon reaction
Entry
R
R’
Time
[h]
4
Ratio
(4/4’)
Yield
with 2 (step C). Because steps A and C are well-
known processes in the copper-catalyzed borylation
reactions of alkynes,[16,17] we conducted a reaction
of 3a with an alkenyl copper species 9, which can
G
[%][b]
1
2
3
4
5
p-tolyl
Ph
Ph
p-tolyl
1b
1c
1d
1e
1 f
1g
1h
1h
1i
1j
1k
1l
1m
1m
1n
1o
1p
1q
1r
28
15
13
2
9
3
15
0.5
24
21
22
26
6
25
24
28
18
5
4b
–
56/44
57/43
52/48
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
–
72
85
86
75
66
71
82
69
81
68
74
70
48[d]
72
42
62
53
63
36
41
4-MeOC6H4
4-BrC6H4
2-thienyl
3,5-(F3C)2C6H4
Me
4c+4’c
4d+4’d
4e+4’e
4 f
4g
4h
5h
4i
4j
4k
Ph
be formed in situ by transmetalation between boryl-
[18]
4-MeOC6H4
Ph
Ph
Ph
Ph
4-MeOC6H4
4-F3CC6H4
4-NCC6H4
nPr
nPr
nBu
CH2OMe
nPent
Ph
nHex
Me3Si
À
stilbene 8 and Cu X (X=OAc or OMe). As de-
6
7
picted in Scheme 2, the reaction led to the smooth
formation of stannylstilbene 10, which confirms the
validity of step B and the proposed catalytic
cycle.[19,20]
Et
Et
8[c]
9
A
10
11
12
13
14[e]
15[e]
16[e]
17[e]
18
19[e]
20
nBu
nBu
nBu
nPr
nPr
nBu
CH2OMe
Me
The generation of the by-product hexabutylditin
(Table 2, entry 13) would be ascribable to the di-
minished reactivity of an aliphatic alkyne toward 6
(step A, Scheme 1), resulting in the formation of
borylstannane 11 through the reaction of 6 with 3a
(Scheme 3). Then, 11 undergoes s-bond metathesis
with a copper methoxide to give stannylcopper spe-
cies 12,[21] which is converted into hexabutylditin by
reaction with 3a. Accordingly, the steric hindrance
of 3c reduces the by-product formation with retard-
ing the interaction with 6, leading to the selective
generation of 4m (Table 2, entry 14).[22]
4l
4m
4m
4n
–
–
–
4o
4p+4’p
4q+4’q
4r+4’r
88/12
93/7
83/17
>99/1
H
H
H
7
27
1s
[a] General procedure: (0.30 mmol, 1 equiv),
(0.39 mmol, 1.3 equiv), CuACHUTNGTERN(NUNG OAc)2 (6.0 mmol, 2 mol%), PCy3 (0.021 mmol, 7 mol%),
toluene (1.0 mL). [b] Yield of isolated product. [c] Trimethyltin tert-butoxide (3b) was
used instead of 3a. [d] NMR yield. [e] Tributyltin tert-butoxide (3c) was used instead
of 3a.
1
2 (0.39 mmol, 1.3 equiv), 3a
Finally, the synthetic utility of the borylstannyla-
tion products was demonstrated by the total synthe-
moieties of which were invariably geminal, was also ob-
served in the reactions of alkyl(aryl)alkynes 1g–l (entries 6–
sis of (Z)-tamoxifen,[23] which has been widely used for the
À
N
treatment of breast cancer (Scheme 4). Thus, the C Sn bond
12).[14] Moreover, a trimethylstannyl moiety could be intro-
duced into product 5h with the same regioselectivity by
using trimethyltin tert-butoxide (3b, entry 8).[15] Aliphatic al-
kynes were found to be less reactive toward the borylstanny-
lation compared to aryl-substituted alkynes: the reaction of
4-octyne (1m) provided 4m in 48% yield, accompanied by
the formation of hexabutylditin as a by-product (entry 13).
of 4h selectively underwent a C C bond-forming reaction
À
under Migita–Kosugi–Stille coupling conditions to afford 13,
which was then transformed into (Z)-tamoxifen (14, 36%
overall yield based on 1h) through a Suzuki–Miyaura cou-
pling with perfect regio- and stereoselectivity.
&
2
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Borylstannylation of Alkynes
FULL PAPER
Scheme 4. Total synthesis of (Z)-tamoxifen: a) see Table 2, entry 8. b) 4h
(1 equiv), 2-(4-iodophenoxy)-N,N-dimethylethanamine (1.5 equiv),
[Pd
(40 mol%), LiCl (10 equiv), DMF, 1008C, dark, 10 h. c) 13 (1 equiv), PhI
(1.5 equiv), [Pd(dba)2] (10 mol%), P(tBu)3 (20 mol%), aqueous KOH
(3m, 3 equiv), THF, 608C, 24 h.
ACHTUNGTREN(UNGN dba)2] (10 mol%, dba=dibenzylideneacetone), CuI (10 mol%), PPh3
A
ACHTUNGTRENNUNG
over, the excellent regio- and stereoselectivity of the boryl-
Scheme 1. A plausible catalytic cycle for the borylstannylation.
À
stannylation and the distinct reactivity of the resulting C
B(Sn) bonds enables the three-step total synthesis of (Z)-ta-
moxifen, which is of pharmacological significance, from
commercially available substrates. Further studies on three-
component borylation reactions with other electrophiles
under copper catalysis, as well as total synthesis of pharma-
cologically active tetrasubstituted alkenes by using boryl-
stannylation products are in progress.
Experimental Section
General procedure for the copper-catalyzed borylstannylation of alkynes:
A Schlenk tube equipped with a magnetic stirring bar was charged with
CuACTHNUTRGEN(NUG OAc)2 (6.0 mmol), tricyclohexylphosphine (20 wt% solution in tol-
Scheme 2. Transformation of an alkenyl–Cu bond into an alkenyl–Sn
bond.
uene, 0.021 mmol) and MeOH (1.0 mL). After the mixture was stirred at
808C for 0.5 h, the solvent was removed in vacuo at room temperature.
An alkyne (0.30 mmol), bis(pinacolato)diboron (0.39 mmol), a tin alkox-
ide (0.39 mmol) and toluene (1.0 mL) were added to the residue, and the
resulting mixture was stirred at room temperature. The mixture was di-
luted with ethyl acetate and filtered through a Celite plug. The organic
solution was washed with brine, dried over MgSO4 and evaporated. The
residual tin alkoxide was removed by column chromatography (10% w/w
anhydrous K2CO3/silica gel; eluent: ethyl acetate), and the product was
isolated by silica-gel column chromatography (eluent: hexane/ethyl ace-
tate). Experimental details and characterization data are provided in the
Supporting Information.
Acknowledgements
We thank Furukawa Technology Promotion Foundation and SEI Group
CSR Foundation for financial support.
Scheme 3. Generation of hexabutylditin.
[1] For reviews, see: a) I. Beletskaya, C. Moberg, Chem. Rev. 1999, 99,
3435; b) M. Suginome, Y. Ito, Chem. Rev. 2000, 100, 3221; c) I. Be-
letskaya, C. Moberg, Chem. Rev. 2006, 106, 2320.
Conclusion
[2] For Si and Sn, see: a) B. L. Chenard, C. M. Van Zyl, J. Org. Chem.
1986, 51, 3561; b) T. N. Mitchell, R. Wickenkamp, A. Amamria, R.
Dicke, U. Schneider, J. Org. Chem. 1987, 52, 4868; c) M. Murakami,
H. Amii, N. Takizawa, Y. Ito, Organometallics 1993, 12, 4223; d) M.
Murakami, T. Matsuda, K. Itami, S. Ashida, M. Terayama, Synthesis
2004, 1522.
We have demonstrated that a copper–phosphine catalytic
system of high availability efficaciously promotes the three-
component borylstannylation of alkynes to provide diverse
vic-borylstannylalkenes in a straightforward manner. More-
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

H. Yoshida et al.
[3] For B and Si, see: a) M. Suginome, H. Nakamura, Y. Ito, Chem.
Commun. 1996, 2777; b) S.-y. Onozawa, Y. Hatanaka, M. Tanaka,
Chem. Commun. 1997, 1229; c) M. Suginome, T. Matsuda, H. Naka-
mura, Y. Ito, Tetrahedron 1999, 55, 8787; d) T. Ohmura, M. Sugi-
nome, Bull. Chem. Soc. Jpn. 2009, 82, 29.
[4] For B and Sn, see: a) S.-y. Onozawa, Y. Hatanaka, T. Sakakura, S.
Shimada, M. Tanaka, Organometallics 1996, 15, 5450; b) L. Weber,
H. B. Wartig, H. G. Stammler, A. Stammler, B. Neumann, Organo-
metallics 2000, 19, 2891; c) R. R. Singidi, T. V. Ra-janBabu, Org.
Lett. 2010, 12, 2622.
[5] Metal-Catalyzed Cross-Coupling Reactions, (Eds: A. de Meijere, F.
Diederich), Wiley-VCH, Weinheim, 2004.
[6] a) R. A. Magarian, L. B. Overacre, S. Singh, K. L. Meyer, Curr.
Med. Chem. 1994, 1, 61; b) V. C. Jordan, J. Med. Chem. 2003, 46,
1081.
[7] a) P. C. Ruenitz, J. R. Bagley, C. M. Mokler, J. Med. Chem. 1982, 25,
1056; b) A. Howell, J. F. R. Robertson, J. Quaresma Albano, A.
Aschermannova, L. Mauriac, U. R. Kleeberg, I. Vergote, B. Erik-
stein, A. Webster, C. Morris, J. Clin. Oncol. 2002, 20, 3396.
[8] a) J. Ellmꢁn, P. Hakulinen, A. Partanen, D. F. Hayes, Breast Cancer
Res. Treat. 2003, 82, 103; b) M. Kusama, K. Miyauchi, H. Aoyama,
M. Sano, M. Kimura, S. Mitsuyama, K. Komaki, H. Doihara, Breast
Cancer Res. Treat. 2004, 88, 1.
the synthesis of allenylboranes) and capture by boron (in the dibory-
lation); for the Cu-catalyzed hydroboration of alkynes, see: a) K. Ta-
kahashi, T. Ishiyama, N. Miyaura, J. Organomet. Chem. 2001, 625,
47; b) J.-E. Lee, J. Kwon, J. Yun, Chem. Commun. 2008, 733; c) Y.
Lee, H. Jang, A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 18234;
d) H.-R. Kim, I.-G. Jung, K. Yoo, K. Jang, E.-S. Lee, J. Yun, S.-U.
Son, Chem. Commun. 2010, 46, 758; e) H.-R. Kim, J. Yun, Chem.
Commun. 2011, 47, 2943; f) Y. Sasaki, Y. Horita, C. Zhong, M. Sa-
wamura, H. Ito, Angew. Chem. 2011, 123, 2830; Angew. Chem. Int.
Ed. 2011, 50, 2778; for the Cu-catalyzed synthesis of allenylboranes,
see: g) H. Ito, Y. Sasaki, M. Sawamura, J. Am. Chem. Soc. 2008,
130, 15774; for the Cu-catalyzed diborylation of alkynes, see ref.
[10].
[14] The palladium-catalyzed borylstannylation of alkylACTHNUTRGENUGN(aryl)alkynes
generally produces a mixture of regioisomers, which is in contrast to
the results described herein; see refs. [4a,c].
[15] The observed regioselectivity in the reaction of alkylACTHNUTRGNE(UNG aryl)alkynes is
ascribable to the exclusive generation of gem-(aryl)alkenyl–copper
species (7, R=Ar, Scheme 1) induced by the electronic directing
effect of the aryl moieties.
[16] a) H. Jang, A. R. Zhugalin, Y. Lee, A. H. Hoveyda, J. Am. Chem.
Soc. 2011, 133, 7859; b) K. Semba, T. Fujihara, J. Terao, Y. Tsuji,
Chem. Eur. J. 2012, 18, 4179; see also ref. [13].
[9] For the synthesis of gem-dimetallated alkenes by insertion reactions
of carbenoids into metal–metal bonds, see: a) T. Hata, H. Kitagawa,
H. Masai, T. Kurahashi, M. Shimizu, T. Hiyama, Angew. Chem.
2001, 113, 812; Angew. Chem. Int. Ed. 2001, 40, 790; b) T. Kuraha-
shi, T. Hata, H. Masai, H. Kitagawa, M. Shimizu, T. Hiyama, Tetra-
hedron 2002, 58, 6381.
[10] H. Yoshida, S. Kawashima, Y. Takemoto, K. Okada, J. Ohshita, K.
Takaki, Angew. Chem. 2012, 124, 239; Angew. Chem. Int. Ed. 2012,
51, 235.
[17] For a computational study, see: L. Dang, H. Zhao, Z. Lin, T. B.
Marder, Organometallics 2008, 27, 1178.
[18] a) A. M. Whittaker, R. P. Rucker, G. Lalic, Org. Lett. 2010, 12, 3216;
b) R. Shintani, K. Takatsu, T. Hayashi, Chem. Commun. 2010, 46,
6822; see also refs. [12a–c].
[19] The present borylstannylation does not proceed through diboryla-
À
tion and subsequent transformation of a C B bond of a diborylal-
À
kene into a C Sn bond, because the Cu-catalyzed diborylation of al-
kynes was found not to occur at room temperature.
[11] For recent examples on Cu-catalyzed reactions by using a diboron,
see: a) H. Ito, Y. Kosaka, K. Nonoyama, Y. Sasaki, M. Sawamura,
Angew. Chem. 2008, 120, 7534; Angew. Chem. Int. Ed. 2008, 47,
7424; b) C. Kleeberg, L. Dang, Z. Lin, T. B. Marder, Angew. Chem.
2009, 121, 5454; Angew. Chem. Int. Ed. 2009, 48, 5350; c) M. Tobisu,
H. Fujihara, K. Koh, N. Chatani, J. Org. Chem. 2010, 75, 4841; d) H.
Ito, T. Toyoda, M. Sawamura, J. Am. Chem. Soc. 2010, 132, 5990;
e) C. Zhong, S. Kunii, Y. Kosaka, M. Sawamura, H. Ito, J. Am.
Chem. Soc. 2010, 132, 11440; f) C.-T. Yang, Z.-Q. Zhang, H. Tajud-
din, C.-C. Wu, J. Liang, J.-H. Liu, Y. Fu, M. Czyzewska, P. G. Steel,
T. B. Marder, L. Liu, Angew. Chem. 2012, 124, 543; Angew. Chem.
Int. Ed. 2012, 51, 528.
[12] For reactions of alkenyl– or aryl–copper species with carbon electro-
philes, see: a) J. Takaya, S. Tadami, K. Ukai, N. Iwasawa, Org. Lett.
2008, 10, 2697; b) T. Ohishi, M. Nishiura, Z. Hou, Angew. Chem.
2008, 120, 5876; Angew. Chem. Int. Ed. 2008, 47, 5792; c) C.-T.
Yang, Z.-Q. Zhang, T.-C. Liu, L. Liu, Angew. Chem. 2011, 123,
3990; Angew. Chem. Int. Ed. 2011, 50, 3904; d) T. Fujihara, T. Xu,
K. Semba, J. Terao, Y. Tsuji, Angew. Chem. 2011, 123, 543; Angew.
Chem. Int. Ed. 2011, 50, 523.
[20] No traces of distannylated alkenes were observed in the present re-
action, which shows that the borylstannylation products do not un-
dergo this boron to tin transformation, probably because of the
steric bulk of the stannyl moieties.
[21] Formation of a silyl copper species by s-bond metathesis between a
copper alkoxide and a borylsilane has been reported; see: a) K.-S.
Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2010, 132, 2898; b) D. J.
Vyas, R. Frçhlich, M. Oestreich, Org. Lett. 2011, 13, 2094; c) P.
Wang, X.-L. Yeo, T.-P. Loh, J. Am. Chem. Soc. 2011, 133, 1254.
[22] The steric hindrance of 3c does not inhibit the interaction of 3c
with 7, which is in contrast to the case with 6. At present, the exact
reason for the different reactivity of 3c toward 6 or 7 is unclear.
[23] For representative examples on the synthesis of (Z)-tamoxifen, see:
a) K. Itami, T. Kamei, J.-i. Yoshida, J. Am. Chem. Soc. 2003, 125,
14670; b) M. Shimizu, C. Nakamaki, K. Shimono, M. Schelper, T.
Kurahashi, T. Hiyama, J. Am. Chem. Soc. 2005, 127, 12506; c) Y.
Nishihara, M. Miyasaka, M. Okamoto, H. Takahashi, E. Inoue, K.
Tanemura, K. Takagi, J. Am. Chem. Soc. 2007, 129, 12634; d) N.
Ishida, Y. Shimamoto, M. Murakami, Org. Lett. 2009, 11, 5434; e) Z.
He, S. Kirchberg, R. Frçhlich, A. Studer, Angew. Chem. 2012, 124,
3759; Angew. Chem. Int. Ed. 2012, 51, 3699.
[13] To date, b-borylalkenyl–copper intermediates have been captured
by protons in the Cu-catalyzed borylations of alkynes with a diboron
to give hydroboration products, except for b-oxygen elimination (in
Received: July 9, 2012
Published online: && &&, 0000
&
4
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Copper-Catalyzed Borylstannylation of Alkynes
FULL PAPER
Synthetic Methods
Y. Takemoto, H. Yoshida,*
K. Takaki ...................... &&&& — &&&&
Copper-Catalyzed Three-Component
Borylstannylation of Alkynes
Borylstannylation: A copper–tricyclo-
hexylphosphine complex was found to
catalyse the three-component boryl-
stannylation of alkynes with a diboron
and a tin alkoxide to afford vic-boryl-
stannylalkenes in a regio- and stereo-
selective manner. Synthetic utility of
the resulting borylstannylation product
was demonstrated by a three-step syn-
thesis of (Z)-tamoxifen from commer-
cially available substrates by successive
Migita–Kosugi–Stille and Suzuki–
Miyaura couplings (see scheme).
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!