Copper-catalyzed α-selective hydrostannylation of alkynes for the synthesis of branched alkenylstannanes

Article abstract of DOI:10.1039/c5cc02720a

A variety of branched alkenylstannanes can directly be synthesized with excellent α-selectivity by the copper-catalyzed hydrostannylation using a distannane or a silylstannane, irrespective of the electronic and steric characteristics of terminal alkynes employed. Synthetic utility of the resulting branched alkenylstannane has been demonstrated by the total synthesis of bexarotene.

Full text of DOI:10.1039/c5cc02720a

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Copper-catalyzed α-selective hydrostannylation of
alkynes for synthesis of branched alkenylstannanes
Cite this: DOI: 10.1039/x0xx00000x
H. Yoshida,*a,b A. Shinke,a Y. Kawanoa and K. Takakia
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
A variety of branched alkenylstannanes can directly be
synthesized with excellent -selectivity by the copper-
catalyzed hydrostannylation using distannane or
α
a
a
silylstannane, irrespective of electronic and steric characters
of terminal alkynes employed. Synthetic utility of the
resulting branched alkenylstannane has been demonstrated
by total synthesis of bexarotene.
In view of high synthetic versatility of alkenylstannanes
especially in carbon–carbon bond-forming processes via
Migita–Kosugi–Stille coupling, tin–lithium exchange reaction,
etc., the development of potent methods for making
alkenylstannanes of defined structure in regio- and
stereoselective manners has continued to be a key subject in
modern synthetic organic chemistry.1 One of the most popular
and straightforward routes to alkenylstannanes would be
hydrostannylation of alkynes,2 and three isomers, namely
adduct and ( )- -adduct, can be generated in the case of
terminal alkynes (eqn (1)).3 Hence the regio- and stereocontrol
of the hydrostannylation is a pivotal issue, and ( )- or ( )-linear
alkenylstannanes have successfully been synthesized with high
α-
E/Z β
Z
E
Scheme 1 Reported α-selective hydrostannylation of terminal alkynes.
β
-selectivity under radical conditions,4 Lewis acid5 or transition
metal catalysis.6
Although selective access to branched the development of a universal system for α-selective
alkenylstannanes has also been achieved in some cases hydrostannylation of terminal alkynes, which gives us a direct
depending upon direct addition of
a
tin hydride7-9 or and efficacious way to such pharmacologically significant 1,1-
stannylmetallation–protonation sequence,10 the existing disubstituted alkenes as bexarotene11 and isocombretastatin A-
methods are still not versatile, owing to limited substrate scope 4,12 has been a long-awaited goal.
on alkynes in every reaction and the use of an excess amount of
We have recently riveted our attention on potential copper
catalysis for metallation reactions of unsaturated carbon–carbon
bonds, and have already disclosed that distannylation13 as well
as various borylations14 of alkynes and alkenes facilely occur to
afford organostannanes and –boranes of structural diversity by
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DOI: 10.1039/C5CC02720A
Table 1 Cu-catalyzed hydrostannylation with a distannanea
Table 2 Cu-catalyzed hydrostannylation with a silylstannanea
Entry
R
Time
(h)
1.5
2
Yield
(%)b
75
2:2’
Products
Entry
R
Time
(h)
43
4
2
2
2
2
3
2
Yield
(%)b
43d
73
74
74
60
48
55
44
3:3’
Products
1
2
nC12H25 (1a)
nC10H21 (1b)
98:2
97:3
2a,2’a
2b,2’b
1c
2
3
4
5
6
7
8
9
nC6H13 (1p)
nC6H13 (1p)
nC8H17 (1q)
nBu (1r)
iAmyl (1s)
iBu (1t)
NC(CH2)3 (1u)
Cl(CH2)3 (1v)
BnO(CH2)2 (1f)
Bn (1w)
>99:1
86:14
88:12
85:15
84:16
92:8
93:7
92:8
88:12
93:7
3p
89
3p,3’p
3q,3’q
3r,3’r
3s,3’s
3t,3’t
3u,3’u
3v,3’v
3f,3’f
3w,3’w
3
1.5
89
97:3
2c,2’c
(1c)
4
5
6
7
8
THPO(CH2)4 (1d)
TBSO(CH2)2 (1e)
BnO(CH2)2 (1f)
HO(CH2)8 (1g)
Br(CH2)8 (1h)
1
1.5
1
3
24
84
85
76
76
43
94:6
96:4
97:3
>99:1
89:11
2d,2’d
2e,2’e
2f,2’f
2g
2
2
55
46
10
2h,2’h
aGeneral procedure: 1 (0.45 mmol, 1.5 equiv), Me3Si–SnBu3 (0.30 mmol, 1
equiv), H2O (0.45 mmol, 1.5 equiv), Cu(OAc)2 (0.03 mol, 10 mol %), PCy3
(0.11 mmol, 35 mol %), toluene (0.2 mL). bIsolated yield. cBu3Sn–SnBu3
was used instead of Me3Si–SnBu3. H2O = 0.4 mL (74 equiv). dNMR yield.
9
8
63
>99:1
2i
(1i)
BnOCH2 (1j)
2-Pyridyl (1k)
10
11
6
5.5
37
68
92:8
>99:1
2j,2’j
2k
12
13
6
68
61
86:14
>99:1
2l,2’l
(1l)
high degrees of α-selectivity in excellent yield (entries 2 and 3),
and furthermore functionalized aliphatic alkynes bearing an
4-nBuC6H4 (1m)
24
2m
acetal (1d), a silyl ether (1e) or a benzyl ether (1f) smoothly
14
2
80
>99:1
2n
underwent the
α-selective hydrostannylation, leaving these
(1n)
reactive moieties intact (entries 4–6). The high functional
group compatibility was also demonstrated by the reaction of a
hydroxyl- (1g) or a bromo-substituted alkyne (1h), and
propargyl-functionalized alkynes (1i and 1j), although the
yields became moderate in some cases (entries 7–10). The
regioselective installation of a stannyl group into an internal
carbon of aromatic terminal alkynes was achieved under the
aGeneral procedure: 1 (0.30 mmol, 1 equiv), Me3Sn–SnMe3 (0.39 mmol, 1.3
equiv), H2O (0.90 mmol, 3 equiv), Cu(OAc)2 (0.015 mol, 5 mol %), PtBu3
(0.053 mmol, 17.5 mol %), toluene (0.2 mL). bIsolated yield.
present conditions as well, and thus pyridyl (1k), naphthyl (1l
and phenyl 1m and 1n acetylenes were efficiently
transformable into the respective branched alkenylstannanes
)
(
)
employing a distannane and a diboron as a metallating reagent.
The distannylation of alkynes was found to proceed through
(
(
2k
1o
–
)
2n) (entries 11–14). An internal alkyne, diphenylacetylene
could participate in the reaction to furnish )-
intermediary formation of a
enough nucleophilicity, which was finally convertible into vic
distannylalkenes by capturing with tin electrophile.
β-stannylalkenylcopper species of
(E
-
trimethylstannylstilbene (2o) as the sole product (eqn (2)),
showing that the hydrostannylation completely proceeds in a cis
fashion.18
a
Therefore, we envisioned that a copper catalyst would also
promote hydrostannylation of alkynes in the presence of a
With the successful synthesis of diverse branched
alkenylstannanes having a trimethylstannyl moiety, we next
suitable protic reagent for trapping the β-stannylalkenylcopper
intermediate.15 Herein we report that the hydrostannylation of
terminal alkynes smoothly takes place under the copper
catalysis by use of water as a protic reagent, and that the
universal system allows a variety of branched alkenylstannanes
investigated
Although
α
-selective installation of a tributylstannyl moiety.
the reaction of 1-octyne 1p with
(
)
hexabutyldistannane in the presence of Cu(OAc)2–PCy3
catalyst19 led to regioselective formation of a branched
alkenylstannane (3p) in moderate yield (Table 2, entry 1), a
silylstannane, tributyl(trimethylsilyl)stannane turned out to
serve as a more effective and reactive stannylating reagent to
to be synthesized with excellent
electronic and steric characters of terminal alkynes.
The -selective hydrostannylation has proven to be feasible
to provide a branched (2a) and a linear (2’a) alkenylstannanes
in 75% yield (2a 2’a = 98:2), when we treated 1-tetradecyne
1a) with hexamethyldistannane and water in toluene at 110 °C
α-selectivity, irrespective of
α
afford a 74% yield of 3p and 3’p (3p:
3’p = 86:14) (entry 2).17
:
It should be noted that a silyl moiety was not incorporated into
an alkyne at all in the reaction with a silylstannane, which is in
marked contrast to the copper-catalyzed selective silyl-
incorporation reactions into unsaturated hydrocarbons with a
(
in the presence of Cu(OAc)2–PtBu3 catalyst (Table 1, entry
1).16,17 The reaction was also applicable to 1-dodecyne (1b
and an imide-substituted alkyne (1c), giving 2b and 2c with
)
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DOI: 1C0.O10M39M/CU5CNCI0C2A72T0IOA N
Scheme 2 Cu-catalyzed deuteriostannylation with deuterium oxide.
Scheme 4 A plausible catalytic cycle for the hydrostannylation.
present
Formation of a stannylcopper species (
metathesis between a distannane (or silylstannane) and Cu–OH
would initiate the hydrostannylation (Scheme 4).22
The
resulting stannylcopper species ( ) then adds across a carbon–
carbon triple bond of a terminal alkyne (stannylcupration) to
produce a -stannylalkenylcopper species ( ), which is finally
transformed into hydrostannylation product through
protonation with water.23
The formation of branched
alkenylstannanes ( and ) with high -selectivity should be
attributable to the regioselective generation of , possessing the
α-selective hydrostannylation.
6
) via σ-bond
6
β
7
a
2
3
α
7
Scheme 3 Total synthesis of bexarotene.
stannyl moiety at the internal carbon, in the stannylcupration
step, which has already been well documented to be kinetically
favored in a stoichiometric reaction of a stannylcopper species
with a terminal alkyne.24
silylborane.20 The hydrostannylation using a silylstannane also
took place smoothly with 1-decyne (1q), 1-hexyne (1r) and
branched aliphatic terminal alkynes (1s and 1t) to provide 3q
3t with high -selectivity (entries 3–6), and furthermore
functionalized terminal alkynes bearing a cyano (1u), a chloro
1v) or a benzyloxy moiety (1f), and 3-phenyl-1-propyne (1w
–
In conclusion, we have developed the universal system for
the α-selective hydrostannylation of terminal alkynes by using
α
a distannane or a silylstannane as a stannylating reagent in the
presence of a copper–trialkylphosphine catalyst, that leads to
the convenient and straightforward method for synthesizing
diverse branched alkenylstannanes, irrespective of electronic
and steric nature of terminal alkynes employed. The resulting
branched alkenylstannane has been demonstrated to be facilely
(
)
were
transformable
into
the
respective
branched
alkenylstannanes (entries 7–10).21
Since water can serve as
a
proton source in the
hydrostannylation, we expected that the present system may be
extend to deuteriostannylation by use of deuterium oxide.
Surprisingly, the copper-catalyzed reaction of 1-tetradecyne
transformable
into
bexarotene of
pharmacologically
significance via the cross-coupling reaction. Further studies on
copper-catalyzed stannylation reactions using a distannane or a
silylstannane are in progress.
(
1a) with hexamethyldistannane in the presence of deuterium
oxide produced dideuteriostannylation product 2a-d2
predominantly (2a- 2 2a- 2a = 79:7:14, eqn (a), Scheme 2).
The formation of 2a-d2 can be rationalized by considering the
deuteriostannylation of 1-tetradecyne- 1a- ), which should be
a
(
)
d
:
d:
Notes and references
Department of Applied Chemistry, Graduate School of Engineering,
d
(
d
a
generated in situ prior to the deuteriostannylation. Actually,
hydrogen–deuterium exchange between 1a and deuterium oxide
was demonstrated to occur smoothly under the copper catalysis
(eqn (b), Scheme 2).
Hiroshima University, Higashi-Hiroshima 739-8527, Japan. Fax: +81-82-
424-5494; Tel: +81-82-424-7724; E-mail: yhiroto@hiroshima-u.ac.jp
b
ACT-C, Japan Science and Technology Agency, Higashi-Hiroshima
739-8527, Japan.
As depicted in Scheme 3, the branched alkenylstannane
†
Electronic Supplementary Information (ESI) available: Experimental
(
2n) was found to be facilely convertible into 1,1-diarylalkene
by the Migita–Kosugi–Stille coupling with ethyl 4-
iodobenzoate. Hydrolysis of the ester moiety of provided
bexarotene in 39% overall yield (3 steps, based on alkyne
4
procedures and characterization data. See DOI: 10.1039/c000000x/
4
1
(
a
) M. Pereyre, J. P. Quintard and A. Rahm, Tin in Organic
Synthesis Butterworth, London, 1987; V. Farina, V.
Krishnamurthy and W. J. Scott, Org. React., 1997, 50, 1; ( ) A. Orita
5
,
(b)
1n), which is widely used as a treatment for cutaneous T-cell
lymphoma,11 demonstrating the synthetic significance of the
c
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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5CC02720A
and J. Otera, Tin in Organic Synthesis, in Main Group Metals in 14 (
Organic Synthesis, ed. H. Yamamoto and K. Oshima, Wiley-VCH,
Weinheim, 2004, pp. 621–720; ( ) T. N. Mitchell, Organotin
a
) H. Yoshida, S. Kawashima, Y. Takemoto, K. Okada, J. Ohshita
and K. Takaki, Angew. Chem. Int. Ed., 2012, 51, 235; (
Takemoto, H. Yoshida and K. Takaki, Chem. Eur. J., 2012, 18
14841; ( ) H. Yoshida, I. Kageyuki and K. Takaki, Org. Lett., 2013,
15, 952; ( I. Kageyuki, H. Yoshida and K. Takaki, Synthesis, 2014,
46, 1924; ( ) H. Yoshida, Y. Takemoto and K. Takaki, Chem.
Commun., 2014, 50, 8299; ( ) Y. Takemoto, H. Yoshida and K.
Takaki, Synthesis, 2014, 46, 3024; ( ) H. Yoshida, Y. Takemoto and
K. Takaki, Asian J. Org. Chem., 2014, , 1204; ( ) H. Yoshida, Y.
Takemoto and K. Takaki, Chem. Commun., 2015, 51, 6297.
b) Y.
d
,
Reagents in Cross-Coupling Reactions, in Metal-Catalyzed Cross-
Coupling Reactions, ed. A. de Meijere and F. Diederich, Wiley-VCH,
c
d
)
Weinheim, 2004, pp. 125–161;
Chemistry, Wiley-VCH, Weinheim, 2004.
) N. D. Smith, J. Mancuso and M. Lautens, Chem. Rev., 2000, 100
3257; ( ) B. M. Trost and Z. T. Ball, Synthesis, 2005, , 853.
For leading references, see: ( ) Y. Ichinose, H. Oda, K. Oshima and
K. Utimoto, Bull. Chem. Soc. Jpn., 1987, 60, 3468; ( ) K. Kikukawa, 15 For stoichiometric formation of a
H. Umekawa, F. Wada and T. Matsuda, Chem. Lett., 1988, 881; (
(e
)
A. G. Davies, Organotin
e
f
2
3
(a
,
g
b
6
3
h
a
b
β-stannylalkenylcopper species,
c
)
followed by its capture with an electrophile including proton, see: (a)
H. X. Zhang, F. Guibé and G. Balavoine, J. Org. Chem., 1990, 55
,
A. Barbero, P. Cuadrado, I. Fleming, A. M. González and F. J.
Pulido, J. Chem. Soc., Chem. Commun., 1992, 351; ( ) A. Barbero, P.
1857.
b
4
(
a
) E. Nakamura, D. Machii and T. Inubushi, J. Am. Chem. Soc.,
1989, 111, 6849; ( ) E. Nakamura, Y. Imanishi and D. Machii, J.
Org. Chem., 1994, 59, 8178; (
N. Fujisawa and A. Hosomi, J. Org. Chem., 2003, 68, 8730; (
Cuadrado, I. Fleming, A. M. González, F. J. Pulido and R. Rubio, J.
Chem. Soc., Perkin Trans. 1, 1993, 1657.
b
c
) K. Miura, D. Wang, Y. Matsumoto, 16 B. Hammond, F. H. Jardine and A. G. Vohra, J. Inorg. Nucl. Chem.
) K. 1971, 33, 1017.
,
d
Miura, D. Wang, Y. Matsumoto and A. Hosomi, Org. Lett., 2005,
7,
17 For optimization of reaction conditions (ligand, protic reagent,
solvent, etc.), see ESI.
503.
5
6
7
(a) N. Asao, J.-X. Liu, T. Sudoh and Y. Yamamoto, J. Chem. Soc., 18 The reaction of 1-phenyl-1-butyne did not give a hydorostannylation
Chem. Commun., 1995, 2405; (
Y. Yamamoto, J. Org. Chem., 1996, 61, 4568; (
X. Liu and Y. Yamamoto, Chem. Commun., 1998, 37.
) R. E. Maleczka, Jr., L. R. Terrell, D. H. Clark, S. L. Whitehead, 20 For representative examples, see: (
W. P. Gallagher and I. Terstiege, J. Org. Chem., 1999, 64, 5958; ( J. Am. Chem. Soc., 2010, 132, 2898; (
A. Darwish, A. Lang, T. Kim and J. M. Chong, Org. Lett., 2008, 10 Angew. Chem. Int. Ed., 2010, 49, 8513; (
861. See also ref. 3 T.-P. Loh, J. Am. Chem. Soc., 2011, 133, 1254; (
) U. Kazmaier, D. Schauss and M. Pohlman, Org. Lett., 1999,
1017; (
Chem., 2000, 2761; (
Chem., 2002, 641, 26; (
J. Org. Chem., 2004, 69, 468; (
Org. Chem., 2007, 2839; ( ) N. Jena and U. Kazmaier, Eur. J. Org.
) H. Lin and U. Kazmaier, Eur. J. Org. Chem.
b
) N. Asao, J.-X. Liu, T. Sudoh and
product.
c
) V. Gevorgyan, J.- 19 The use of such Cu(I) source as CuCl (with NaO
thiophene-2-carboxylate resulted in lower yield.
) A. H. Hoveyda and K.-S. Lee,
) D. J. Vyas and M. Oestreich,
) P. Wang, X.-L. Yeo and
) T. Fujihara, Y.
tBu) and Cu(I)-
(a
a
b
)
b
,
c
c
.
d
(a
1
,
Tani, K. Semba, J. Terao and Y. Tsuji, Angew. Chem. Int. Ed., 2012,
51, 11487.
b
) U. Kazmaier, M. Pohlman and D. Schauß, Eur. J. Org.
c
) S. Braune and U. Kazmaier, J. Organomet. 21 The relatively lower yields with TMSSnBu3 compared with those
d
) S. Braune, M. Pohlman and U. Kazmaier,
) H. Lin and U. Kazmaier, Eur. J.
with Me3SnSnMe3 are ascribable to formation of Bu3SnSnBu3 as a
by-product, which has been demonstrated to occur only in the
presence of a Cu catalyst and a proton source. See ESI for details.
22 For generation of a stannylcopper species by use of a distannane or a
e
f
Chem., 2008, 3852; (
g
,
2009, 1221.
silylstannane, see: (
Aksela, S. Sharma and S. M. Singh, Tetrahedron Lett., 1990, 31, 165;
) B. H. Lipshutz, D. C. Reuter and E. L. Ellsworth, J. Org. Chem.
1989, 54, 4975.
23 Addition of a stannylcopper species to an alkyne and subsequent
protonation of the resulting -stannylalkenylcopper species have been
established steps in the stoichiometric stannylcupration of alkynes.
See: ( ) A. Barbero and F. J. Pulido, Chem. Soc. Rev., 2005, 34, 913;
) F. J. Pulido and A. Barbero, Silyl and Stannyl Derivatives of
a) A. C. Oehlschlager, M. W. Hutzinger, R.
8
9
A. Hamze, D. Veau, O. Provot, J.-D. Brion and M. Alami, J. Org.
Chem., 2009, 74, 1337.
(
b
,
I. Shibata, T. Suwa, K. Ryu and A. Baba, J. Am. Chem. Soc., 2001,
123, 4101.
10 (
Tetrahedron Lett., 1984, 25, 2151; (
Morizawa, K. Oshima and H. Nozaki, J. Organomet. Chem., 1985,
285, 163; (c) S. Sharma and A. C. Oehlschlager, Tetrahedron Lett.
1986, 27, 6161; ( ) S. Sharma and A. C. Oehlschlager, Tetrahedron
Lett., 1988, 29, 261; ( ) S. Sharma and A. C. Oehlschlager, J. Org.
Chem., 1989, 54, 5064.
a
) J. Hibino, S. Matsubara, Y. Morizawa, K. Oshima and H. Nozaki,
β
b
) S. Matsubara, J. Hibino, Y.
a
,
(b
d
Organocopper Compounds, in The Chemistry of Organocopper
Compounds, ed. Z. Rappoport and I. Marek, John Wiley & Sons,
Chichester, 2009, pp. 775–856.
e
11 T. Illidge, C. Chan, N. Counsell, S. Morris, J. Scarisbrick, D. Gilson, 24 R. D. Singer, M. W. Hutzzinger and A. C. Oehlschlager, J. Org.
B. Popova, P. Patrick, P. Smith, S. Whittaker and R. Cowan, Br. J.
Cancer, 2013, 109, 2566.
Chem., 1991, 56, 4933.
12 J. Aziz, E. Brachet, A. Hamze, J.-F. Peyrat, G. Bernadat, E. Morvan,
J. Bignon, J. Wdzieczak-Bakala, D. Desravines, J. Dubois, M. Tueni,
A. Yassine, J.-D. Brion and M. Alami, Org. Biomol. Chem., 2013,
11, 430.
13 H.Yoshida, A. Shinke and K. Takaki, Chem. Commun., 2013, 49
,
11671.
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