Borylstannylation of alkynes with inverse regioselectivity: Copper-catalyzed three-component coupling using a masked diboron

Article abstract of DOI:10.1039/c5cc00439j

A variety of terminal alkynes are facilely convertible into cis-boryl(stannyl)alkenes with inverse regioselectivity to those of the previous borylstannylation by the copper-catalyzed three-component reaction using a masked diboron. The synthetic utility of the resulting boryl(stannyl)alkenes has been demonstrated by chemoselective coupling reactions. This journal is

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DOI: 10.1039/C5CC00439J
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Borylstannylation
of
alkynes
with
inverse
regioselectivity: Copper-catalyzed three-component
coupling using a masked diboron
Cite this: DOI: 10.1039/x0xx00000x
H. Yoshida,*a,b Y. Takemotoa and K. Takakia
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
A variety of terminal alkynes are facilely convertible into cis-
boryl(stannyl)alkenes with regioselectivity inverse to those of
the previous borylstannylation by the copper-catalyzed three-
component reaction using a masked diboron. Synthetic
utility of the resulting boryl(stannyl)alkenes has been
demonstrated by chemoselective coupling reactions.
Pd-catalyzed borylstannylation
Me
B
N
N
Me3Sn
Me
Pd(PPh3)4
Transition metal-catalyzed dimetallation of alkynes has
commanded considerable attention,1 because it provides
convenient and direct method for constructing regio- and
stereo-defined dimetallated alkenes, whose carbon–metal bonds
are utilizable for carbon–carbon bond-forming processes2 to
give multisubstituted alkenes, which constitute an important
class of biologically and pharmaceutically active molecules.
One of the most valuable dimetallations would be
borylstannylation, in which the resulting hetero-dimetallic
moieties can tandemly undergo chemoselective cross-coupling
Sn
B
R
(pin)B B(pin)
R
Bu3SnOMe
Cu(OAc)2
PCy3
O
B(pin) =
B
O
Cu-catalyzed three-component borylstannylation
Scheme 1 Reported borylstannylation of terminal alkynes.
reactions
(Suzuki–Miyaura3
and
Migita–Kosugi–Stille
coupling4) with high functional group compatibility under
controlled reaction conditions. Since the pioneering work was
reported by Tanaka,5a the borylstannylation has hitherto been
achieved by direct insertion of alkynes into a B–Sn bond of
borylstannanes under palladium catalysis.5 On the other hand,
(Scheme 1), and thus we have focused our attention on reversal
of regioselectivity, which increases structural diversity of vic-
boryl(stannyl)alkenes and thereby broadens the synthetic utility
of the borylstannylation. Herein we report that the use of a
masked diboron9 in the copper-catalyzed three-component
borylstannylation of terminal alkynes completely inverts the
regioselectivity, and that this method provides convenient and
direct entry to unprecedented hetero-dimetallated alkenes
having masked boryl and stannyl moieties.10
we have recently disclosed
a different mode of the
borylstannylation by copper-catalyzed three-component
a
coupling using a diboron and a tin alkoxide.6-8 Irrespective of
the catalytic systems and the reaction modes, terminal alkynes
exclusively accept regioselective addition of the boryl group at
the terminal carbon and the stannyl group at the internal carbon
in a cis fashion to give (Z)-1-boryl-2-stannyl-1-alkenes
First we conducted the reaction of 1-octyne (1a) with a
masked diboron ((pin)B–B(dan), pin: pinacolato, dan:
naphthalene-1,8-diaminato11) and tributyltin methoxide in THF
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Table 1 Ligand effect on Cu-catalyzed borylstannylation of 1-octynea
Table 2 NHC–Cu-catalyzed borylstannylation of terminal alkynes a
View Article Online
(dan)B
SnBu
(dan)B
SnBu3
DOI: 10.1039/C5CC003439J
R
nHex
Bu3SnOMe (2 equiv)
(SIPr)CuCl (2 mol%)
Bu3SnOMe (1.2 equiv)
Cu catalyst (2 mol%)
2
2a
+
:
(pin)B B(dan)
1.2
+
:
nHex
(pin)B B(dan)
1.2
R
THF, rt, 1 h
THF, rt
1
1
Bu3Sn
R
B(dan)
Bu3Sn
B(dan)
H
B
H
1
1a
nHex
N
N
2'
B(dan) =
2'a
Entry
R
Yield (%)b
2:2’c
94:6
99:1
94:6
99:1
95:5
99:1
99:1
Products
2b, 2’b
2c, 2’c
2d, 2’d
2e, 2’e
2f, 2’f
2g, 2’g
2h, 2’h
2i
2j
2k
2l
2m
1
2
3
4
5
6
7
8
nBu (1b)
iBu (1c)
78
81
74
87
79
81
73
66
66
66
69
75
R3
R1
R1
R1
R1
Ph(CH2)2 (1d)
Br(CH2)2 (1e)
NC(CH2)3 (1f)
1-Cyclohexenyl (1g)
Ph (1h)
MeOCH2 (1i)
BnOCH2 (1j)
THPOCH2 (1k)
Et2NCH2 (1l)
Me3Si (1m)
N
N
N
N
R1
R1
R1
R1
R2
R2
Cu
Cl
Cu
Cl
R2
R2
SIPr: R1 = iPr, R2 = R3 = H
SIMes: R1 = R2 = Me, R3 = H
tBu-SIPr: R1 = iPr, R2 = H, R3 = tBu
IPr: R1 = iPr, R2 = H
IPr*: R1 = Ph2CH, R2 = Me
>99:1
>99:1
>99:1
>99:1
>99:1
9
Entry Cu catalyst
Time (h)
Yield (%)b
2a:2’ac
10
11
12
1
2
3
4
(SIPr)CuCl
(SIMes)CuCl
(tBu-SIPr)CuCl
(IPr)CuCl
7
2
20
5
11
2
48
14
10
74
81
69
75
80
81
75
60
86
96:4
90:10
94:6
96:4
96:4
93:7
44:56
84:16
96:4
a
General procedure: 1 (0.30 mmol, 1 equiv), (pin)B–B(dan) (0.36 mmol, 1.2
equiv), Bu3SnOMe (0.60 mmol, 2 equiv), (SIPr)CuCl (6.0 µmol, 2 mol%),
THF (1 mL). b Isolated yield. c Determined by 1H NMR.
5
(IPr*)CuCl
6d
7
P(tBu)3, CuCl
(PPh3)3CuCl
PCy3, CuCl
(SIPr)CuCl
8d
9e
diyne
SnBu3
a
(dan)B
General procedure: 1a (0.30 mmol, 1 equiv), (pin)B–B(dan) (0.36 mmol,
1.2 equiv), Bu3SnOMe (0.36 mmol, 1.2 equiv), Cu catalyst (6.0 µmol, 2
mol%), THF (1 mL). b Isolated yield. c Determined by 1H NMR. d Ligand =
4 mol%. e Bu3SnOMe = 2 equiv.
(pin)B–B(dan) (2.4 equiv)
Bu3SnOMe (2.4 equiv)
(SIPr)CuCl (2 mol%)
THF, rt, 8 h
(dan)B
at room temperature in the presence of an N-heterocyclic
carbene (NHC)-coordinated copper complex ((SIPr)CuCl), and
found that the cis-borylstannylation took place with
regioselectivity inverse to those of the previous
borylstannylation (74% yield, 2a:2’a = 96:4), leading to the
introduction of the boryl group at the internal carbon and the
stannyl group at the terminal carbon (Table 1, entry 1). It is
noteworthy that the B(dan) moiety was solely installed in the
product, and a borylstannylation product having the B(pin)
moiety was not formed at all. The regioselectivity for the
formation of 2a was generally high with bulky ligands (SIMes,
tBu-SIPr, IPr, IPr*12 and P(tBu)3) (entries 2–6), whereas the use
of triphenylphosphine ((PPh3)3CuCl) led to the formation of
regioisomeric mixtures (2a:2’a = 44:56, entry 7). In addition,
the reaction with PCy3, used for the previous borylstannylation
with bis(pinacolato)diboron,6a also afforded 2a preferentially
(2a:2’a = 84:16, entry 8), which reveals that the choice of a
diboron as well as a ligand is the key for the present
regioselectivity.13 Since the increase in an amount of tributyltin
methoxide resulted in the increase in the yield with the highest
regioselectivity (86% yield, entry 9), we selected the conditions
for further studies.14
SnBu3
1 equiv
1n
2n: 58%
allene
Bu3SnOMe (1.2 equiv)
(IMes)CuCl (2 mol%)
B(dan)
•
+
:
(pin)B B(dan)
1.2
R
THF, rt, 1 h
R
SnBu3
1
3a: R = nOct
3b: R = Ph
4a: 72%
4b: 65%
Me
Me
N
N
Me
Me
Cu
Cl
Me
Me
(IMes)CuCl
Scheme 2 Borylstannylation of a diyne and allenes.
borylstannylation with high degrees of regioselectivity to give
2b, 2c and 2d in 78, 81 and 74% yield (entries 1–3). The
functional group compatibility of the reaction was sufficiently
high, and thus a C–Br bond15 in 1e and a cyano group in 1f
remained intact throughout the reaction (entries 4 and 5). The
present regioselectivity was also observed by using enyne 1g
and phenylacetylene 1h (entries 6 and 7), and furthermore the
reaction of propargyl ethers (1i and 1j) or a THP-protected
propargyl alcohol (1k) resulted in the exclusive formation of
2i–2k (entries 8–10). In addition, propargyl amine 1l and
trimethylsilylacetylene 1m accepted the addition of the B(dan)
moiety at their internal carbon with perfect regioselectivity
(entries 11 and 12).16 The versatility of the borylstannylation
With the optimum conditions in hand (Table 1, entry 9), the
substrate scope on alkynes was next investigated (Table 2).
Such aliphatic terminal alkynes as 1-hexyne (1b), 4-methyl-1-
pentyne (1c) and 4-phenyl-1-butyne (1d) also underwent the
2 | J. Name., 2012, 00, 1-3
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(SIPr)Cu–Cl
(dan)B
R
SnBu3
(dan)B
R
SnBu3
Bu3SnOMe
Bu3SnCl
View Article Online
DOI: 10.1039/C5CC00439J
2
(SIPr)Cu–OMe
4-MeC6H4I (1.2 equiv)
Pd2(dba)3 (1 mol%)
XPhos (3 mol%)
LiCl (1 equiv)
CuCl (2.5 equiv)
DMF, rt, 3 h
(pin)B B(dan)
Bu3SnOMe
DMF, 100 °C, 1 h
step C
Me
(SIPr)Cu OMe
(dan)B B(pin)
(dan)B
R
Cu(SIPr)
R
(dan)B
R
(dan)B
B(dan)
MeO
step B
step A
5: 82%
6: R = nHex, 97%
7: R = Ph, 90%
8: R = CH2OMe, 90%
R
(pin)BOMe
(SIPr)Cu–B(dan)
pinacol (8 equiv)
6M H2SO4 (6 equiv)
THF, 50 °C, 48 h
Scheme 3 A plausible catalytic cycle for borylstannylation.
‡
Ph
(dan)B
CuL
(pin)B
Ph
B(pin)
R
R
(dan)B
SnBu3
52%
+
R
4-MeC6H4I (2.6 equiv)
PdCl2(dppf)•CH2Cl2 (5 mol%)
K3PO4 (12 equiv)
LCu
B(dan)
LCu–B(dan)
DMSO, 45 °C, 24 h
R
Me
Scheme 4 Regioselectivity in the borylcupration.
Ph
was further expanded by application to 1,7-octadiyne17 (1n) and
allenes18 (3a and 3b): both of the triple bonds were convertible
regioselectively into the borylstannylalkenes in the former case,
and the regio- and stereoselective reaction proceeded to provide
(Z)-1-stannyl-2-boryl-2-alkenes (4a and 4b) as the single
product, although the regioselectivity is similar to that of the
previous borylstannylation with bis(pinacolato)diboron6b in the
latter case (Scheme 2).
Ph
Me
9: 65%
Scheme 5 Transformation of borylstannylation products.
Synthetic utility of the boryl(stannyl)alkenes was
demonstrated by the chemoselective cross-coupling: a C–Sn
bond of 2i was solely convertible into a C–C bond by the
palladium-catalyzed Migita–Kosugi–Stille reaction to provide
an 82% yield of 5 with a masked boryl moiety remaining intact
(Scheme 5). Furthermore, the masking enabled the copper-
mediated oxidative homocoupling to take place at the C–Sn
bond selectively, affording 1,4-diboryl-1,3-butadienes (6–8)
stereoretentively in high yield. Unmasking of the resulting 1,4-
diboryl-1,3-butadiene, followed by the Suzuki–Miyaura
reaction with 4-iodotoluene furnished 1,1,4,4-tetraarylbutadiene
9.
In conclusion, we have disclosed that the borylstannylation
of terminal alkynes proceeds with inverse regioselectivity by
the copper-catalyzed three-component reaction using a masked
diboron, which gives us convenient and potent approach to
diverse cis-boryl(stannyl)alkenes bearing the masked boryl
moiety at the internal carbons. Moreover, synthetic versatility
of the resulting boryl(stannyl)alkenes has been shown by the
chemoselective coupling reactions depending on the difference
in the reactivity between the masked boryl and the stannyl
moieties. Further studies on copper-catalyzed borylation
Similarly
to
the
previous
copper-catalyzed
borylstannylation with bis(pinacolato)diboron,6 generation of a
borylcopper species, Cu–B(dan), from Cu–OMe and a masked
diboron commences the reaction (Scheme 3, step A).
Subsequent insertion of an alkyne into the Cu–B(dan) bond
which produces a β-borylalkenylcopper species (borylcupration,
step B),19 followed by capturing with a tin methoxide furnishes
the product (step C).20 The formation of Cu–B(dan) (vs. Cu–
B(pin)) can be rationally explained by selective interaction
between the Lewis acidic B(pin) moiety of (pin)B–B(dan) and
the methoxy moiety of Cu–OMe in step A, leading to the
exclusive introduction of the masked boryl moiety across the
triple bond of alkynes. The orientation of a borylcopper species
in the borylcupration step entirely governs the regiochemical
outcome of the borylstannylation (Scheme 4), and the mode of
the borylcupration with Cu–B(dan) would simply be controlled
by steric repulsion between a substituent on alkynes and a
bulkier copper moiety as was the case with the
hydroboration.10a Hence, the B(dan) moiety is solely installed
into the internal carbon of terminal alkynes,21,22 which results in
the inverse regioselectivity in the present borylstannylation.
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reactions by use of a masked diboron as well as on details of
the mechanism are in progress.
12 (a) G. Berthon-Gelloz, M. A. Siegler, A. L. Spek, B. Tinant, J. N. H.
Reek and I. E. Markó, Dalton Trans., 2010, 39, 1444; (b) J. Balogh,
View Article Online
A. M. Z. Slawin and S. P. Nolan, Organometallics, 2012, 31, 3259.
DOI: 10.1039/C5CC00439J
13 A boryl moiety is selectively installed into a terminal carbon of 1-
octyne in the borylstannylation with bis(pinacolato)diboron under the
Cu–PCy3 catalysis, which is in marked contrast to the results
described herein. See ref. 6a.
Notes and references
Department of Applied Chemistry, Graduate School of Engineering,
a
Hiroshima University, Higashi-Hiroshima 739-8527, Japan. Fax: +81-82-
424-5494; Tel: +81-82-424-7724; E-mail: yhiroto@hiroshima-u.ac.jp
14 The alkyne (1a) had already been consumed at the time indicated in
Table 1, and thus the yields would not change if the reactions are left
longer.
b
ACT-C, Japan Science and Technology Agency, Higashi-Hiroshima
739-8527, Japan.
†
Electronic Supplementary Information (ESI) available: Experimental
15 For copper-catalyzed borylation of alkyl halides with a diboron, see:
(a) C.-T. Yang, Z.-Q. Zhang, H. Tajuddin, C.-C. Wu, J. Liang, J.-H.
Liu, Y. Fu, M. Czyzewska, P. G. Steel, T. B. Marder and L. Liu,
Angew. Chem. Int. Ed., 2012, 51, 528; (b) H. Ito and K. Kubota, Org.
Lett., 2012, 14, 890.
procedures and characterization data. See DOI: 10.1039/c000000x/
1
For reviews, see: (a) I. Beletskaya and C. Moberg, Chem. Rev., 1999,
99, 3435; (b) M. Suginome and Y. Ito, Chem. Rev., 2000, 100, 3221;
(c) I. Beletskaya and C. Moberg, Chem. Rev., 2006, 106, 2320.
Metal-Catalyzed Cross-Coupling Reactions, ed. A. de Meijere and F.
Diederich, Wiley-VHC, Weinheim, 2004.
16 The reaction of ethyl propiolate did not produce the borylstannylation
product at all.
2
3
17 For palladium-catalyzed cyclizative borylstannylation of diynes with
a borylstannane, see: (a) R. R. Singidi and T. V. RajanBabu, Org.
Lett., 2008, 10, 3351; (b) R. R. Singidi, A. M. Kutney, J. C. Gallucci
and T. V. RajanBabu, J. Am. Chem. Soc., 2010, 132, 13078. See also
ref. 5b.
(a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457; (b) N.
Miyaura, Top. Curr. Chem., 2002, 219, 11.
4
5
V. Farina,V. Krishnamurthy and W. J. Scott, Org. React., 1997, 50, 1.
(a) S. Onozawa, Y. Hatanaka, T. Sakakura, S. Shimada and M.
Tanaka, Organometallics, 1996, 15, 5450; (b) S. Onozawa, Y.
Hatanaka, N. Choi and M. Tanaka, Organometallics, 1997, 16, 5389;
(c) L. Weber, H. B. Wartig, H.-S. Stammler, A. Stammler and B.
Neumann, Organometallics, 2000, 19, 2891; (d) R. R. Singidi and T.
V. RajanBabu, Org. Lett., 2010, 12, 2622.
18 Palladium-catalyzed borylstannylation of an allene with
a
borylstannane is accompanied by dimerization of an allene. See: S.
Onozawa, Y. Hatanaka and M. Tanaka, Chem. Commun., 1999, 1863.
19 Generation of a borylcopper species (step A) and insertion of an
alkyne into the Cu–B bond (step B) have been widely accepted as
fundamental elementary steps in the copper-catalyzed borylation
reactions of alkynes with diborons. See ref. 8.
6
7
(a) Y. Takemoto, H. Yoshida and K. Takaki, Chem. Eur. J., 2012, 18,
14841; (b) Y. Takemoto, H. Yoshida and K. Takaki, Synthesis, 2014,
46, 3024.
20 We have already verified that an alkenylcopper species is facilely
captured with a tin methoxide to produce an alkenylstannane. See ref.
6a.
We have also reported copper-catalyzed borylation and stannylation
reactions of alkynes and alkenes. See: (a) H. Yoshida, S. Kawashima,
Y. Takemoto, K. Okada, J. Ohshita and K. Takaki, Angew. Chem. Int.
Ed., 2012, 51, 235; (b) H. Yoshida, I. Kageyuki and K. Takaki, Org.
Lett., 2013, 15, 952; (c) H. Yoshida, A. Shinke and K. Takaki, Chem.
Commun., 2013, 49, 11671; (d) I. Kageyuki, H. Yoshida and K.
Takaki, Synthesis, 2014, 46, 1924.
21 Installation of a B(pin) moiety into a terminal carbon of terminal
alkynes is commonly observed in copper-catalyzed hydroboration
with (pin)B–B(pin). See: (a) J.-E. Lee, J. Kwon and J. Yun, Chem.
Commun., 2008, 733; (b) Y. Lee, H. Jang and A. H. Hoveyda, J. Am.
Chem. Soc., 2009, 131, 18234; (c) H. Jang, A. R. Zhugralin, Y. Lee
and A. H. Hoveyda, J. Am. Chem. Soc., 2011, 133, 7859.
8
9
For a review on copper-catalyzed borylation reactions of alkynes with
diborons, see: (a) J. Yun, Asian. J. Org. Chem., 2013, 2, 1016; (b) T.
Fujihara, K. Semba, J. Terao and Y. Tsuji, Catal. Sci. Technol., 2014,
4, 1699.
22 α-Selective hydroboration of terminal alkynes with (pin)B–B(pin)
proceeds in the presence of a copper catalyst coordinated by a
sterically demanding ligand (P(tBu)3, SIMes or SIPr), however, the
substrate scope is limited to propargyl-functionalized and electron-
deficient aryl ones, being in marked contrast to the results described
herein. See: A. L. Moure, P. Mauleón, R. G. Arrayás and J. C.
Carretero, Org. Lett., 2013, 15, 2054. See also ref. 21c.
(a) N. Iwadate and M. Suginome, J. Am. Chem. Soc., 2010, 132,
2548; (b) N. Miralles, J. Cid, A. B. Cuenca, J. J. Carbó and E.
Fernández, Chem. Commun., 2015, 51, 1693.
10 We have recently reported copper-catalyzed hydroboration of alkynes
and alkenes with a masked diboron. See: (a) H. Yoshida, Y.
Takemoto and K. Takaki, Chem. Commun., 2014, 50, 8299; (b) H.
Yoshida, Y. Takemoto and K. Takaki, Asian J. Org. Chem., 2014, 3,
1204.
11 For boron-masking strategy with 1,8-diaminonaphthalene, see: (a) H.
Noguchi, K. Hojo and M. Suginome, J. Am. Chem. Soc., 2007, 129,
758; (b) H. Noguchi, T. Shioda, C.-M. Chou and M. Suginome, Org.
Lett., 2008, 10, 377; (c) N. Iwadate and M. Suginome, Org. Lett.,
2009, 11, 1899; (d) N. Iwadate and M. Suginome, Chem. Lett., 2010,
39, 558.
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