Regio- and stereoselectivity in stannyl- and silylcupration of alkynes and enynes using proton sources

Article abstract of DOI:10.1055/s-1998-1864

Stannylcupration of alkyne 6 was performed using different proton sources such as phenols, alcohols and water; results showed that the cuprate reagent was not affected during the reaction. In all cases tested in presence of a proton source, the vinylstann

Full text of DOI:10.1055/s-1998-1864

October 1998
SYNLETT
1129
Regio- and Stereoselectivity in Stannyl- and Silylcupration of Alkynes and Enynes Using
Proton Sources
Jean-François Betzer, Ange Pancrazi *
Laboratoire de Synthèse Organique, Ecole Polytechnique, DCSO, 91128, Palaiseau, France.
Fax: (33) 01 69 33 30 10. E-mail : pancrazi@poly.polytechnique.fr
Received 9 July 1998
6
Abstract: Stannylcupration of alkyne 6 was performed using different
proton sources such as phenols, alcohols and water; results showed that
the cuprate reagent was not affected during the reaction. In all cases
the kinetic adduct, to the (E)-derivative. Stannylation of alkynes using
the Me SnCu•Me S reagent and MeOH addition (60 equiv.) was also
reported by this author as well as the use of acetic acid as proton source!
An interesting NMR study was realized by Oehlschlager, proving that
3
2
7
tested in presence of
a
proton source, the vinylstannane 10
corresponding to a trans addition was not produced, while the distal and
proximal isomers 8 and 9 resulting from a cis addition were obtained in
good yield. The 8/9 ratio was dependent on the reaction temperature, the
acidity and the number of equivalents of the proton source. This study
was also extended to the stannylcupration of enynes and silylcupration
of alkynes and enynes.
the intermediate vinylcuprate was quenched by methanol and also that
the proximal stannyl derivative was the kinetic product in
stannylcupration of alkynes.5
,8
In this study we report stannyl- and silylcuprations of alkynes and
enynes under different conditions involving addition of different proton
sources to the cuprate solution.
Using the higher order (Bu Sn) CuCNLi cyanocuprate,9 (4 equiv.,
3
2
2
In total synthesis of natural products, the problem of stereoselective
construction of some unsaturated fragments has been resolved in many
cases by the use of vinyl- or dienylstannanes which can be considered as
important building blocks in this area. Stereoselective preparation of
dienic or trienic systems from vinyl-and/or dienylstannanes was effected
via transition-metal catalyzed cross-coupling reactions and/or tin-
lithium exchange reactions as key reactions which proceeded with total
retention of the geometry of vinyl or dienyl precursors.1 For the
stereoselective synthesis of (Z)- and/or (E)-vinylic stannanes,
THF, -10°C, 12 h) and no additive, stannylcupration of alkyne 6 gave a
30:70 mixture of vinylstannanes 8 and 10 in 82% yield (Scheme 2, table
1, entry 1).3 The pure distal derivative 8 was obtained in good yield
(70%) when MeOH (110 equiv.) was added to the cuprate solution and
when reaction was carried out at -10°C for 12 h; compound 9 was not
obtained under these conditions nor the vinylstannane isomer 10 (Table
1, entry 2).
,10
2
3
stannylcuprations and Pd-catalyzed hydrostannylations of alkynes and
enynes have become for the last ten years the most utilized methods in
total synthesis.
In a preceding work,4 an efficient preparation of pure substituted
dienylstannanes such as 3 and 4 (72% and 64% yield respectively) was
described by stannylcupration of enynols 1 and 2 using methanol as a
proton source while standard conditions did not work (Scheme 1). The
same reaction applied to alkynes 5 and 6 [(Bu Sn) CuCNLi , THF/
3
2
2
MeOH (110 equiv.), -10°C, 12h] also only gave the distal stannyl
derivatives 7 and 8 in good yields (71% and 70% respectively).
Scheme 2
Scheme 1
Addition of a proton source such as MeOH or EtOH (1 to 2 equiv.) was
first described by Piers and coworkers in 1980 for stannylcupration of
5
When phenol (30 equiv.) was added to the cuprate solution,11,12 reaction
α,β-acetylenic esters; addition of MeOH led in this case, by trapping of
performed at -10°C led to the formation of distal and proximal

1
130
LETTERS
SYNLETT
1
6
regioisomers 8 and 9 in 88% yield and a 86:14 ratio (Table 1, entry 3); in
this case the more acidic phenol (pKa = 10.0) was able to trap the kinetic
proximal stannane 9 more efficiently than methanol (pKa = 15.5).
Similar results were obtained with acetic acid (pKa = 4.6) and 2,4-
dinitrophenol (pKa = 4.1) and stannylcupration of 6 proceeded
respectively in 78 and 85% yield, compounds 8 an 9 were produced in a
In another application of these results, silylcupration of enyne 1 was
1
7
realized by reaction with (Me PhSi) CuCNLi
2
without additive. A
2
2
73:27 mixture of isomers 13 and 14 was obtained in 95% yield (Scheme
4). The same reaction using 7 equivalents of water gave only the pure
distal silyl compound 13 in 94% yield.18
85:15 ratio (Entries 4 and 5). When a more acidic additive such as 2,4,6-
trinitrophenol (pKa = 0.3) was added to the cuprate solution no reaction
occurred (Entry 6) and the cuprate reagent seemed to be destroyed.
When stannylcupration was performed at lower temperature, - 40°C, in
the cases where MeOH and 2,4-dinitrophenol were added to the cuprate
solution, yields increased to 95% and stannane 9 was obtained in
slightly better yields (Table 1, entries 8 and 9, respectively 85:15 and
78:22 ratios).
These results clearly establish that regioisomeric control is closely
related to the reaction temperature. Addition of a proton source to the
cuprate solution as an internal quench, can then increase the yield of the
proximal stannyl derivative. The second, but important, positive effect
of the addition of the proton source is to ensure the effective quench of
the stannylcuprate adducts to give the stannyl derivatives. When the
1
3
proton source has
a
pKa
>
5
the higher cyanocuprate
(
(
Bu Sn) CuCNLi is not destroyed even under drastic conditions
-10°C, 12 h). In all the cases we examined, the vinylstannane 10
3
2
2
resulting from a trans addition was never obtained when a proton source
was used.
Scheme 4
We also decided to use water as a proton source14 and surprisingly the
When alkyne 6 was treated under the same drastic conditions (-10°C,
yield increased to 97% and vinylstannanes 8 and 9 were obtained in a
1
0 h), vinylsilane 15 was first obtained in a modest 71% yield when no
1
5
8
5:15 ratio (Entry 7). In this reaction 10 equivalents of water were
additive was used, and in 98% yield when 7 equivalents of water were
added.
added to the cuprate which was not destroyed even after 10-12h reaction
time.
Silylcuprates also could be used in presence of water even when the
reaction was carried out at -10°C for 12 h. Yields increased and the pure
distal derivative was obtained.
In this particular case, water presents an intermediate acidity between
methanol and phenol (pKa = 14), and only 10 equivalents of water were
enough to give an excellent yield. This water effect cannot be at this
time related to the pKa value and no explanation could be given without
other experiments.
In this study it was shown that alcohols, phenol, acetic acid and water
could be added to a solution of stannyl or silyl cuprate without damage
to the reaction. Moreover beneficial effects were observed such as an
increase in the overall yield and no formation of trans adduct or by-
The scope of the reaction was extended to enynes. Treatment of enyne 1
with (Bu Sn) CuCNLi gave only the distal diennylstannane 3 in 72%
3
2
2
19
products.
yield when methanol (110 equiv.) was added (Scheme 3); interestingly
In adjusting the reaction temperature, the pKa (> 4 or 5) and the number
of equivalents of the proton source, stannylcupration reactions can be
modulated either towards the formation of pure distal adduct (high
temperature) or to yield more of the proximal product (low temperature)
addition of 10 equiv. of water to the cuprate solution led to stannane 3 in
80% yield and starting material 1 was recovered in 20% yield.
Acknowledgments: The CNRS and the Ecole Polytechnique are
acknowledged for financial support and we thank Rhône-Poulenc Rorer
for a fellowship for J.-F. B and Dr Joëlle Prunet for helpful discussions.
References and Notes
(
1) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic Synthesis:
Butterworths: London 1987.
(
2) For stannylcupration of enynes see: Oehlschlager, A. C.
Tetrahedron 1991, 47, 1163. Yokokawa, F.; Hamada, Y.; Shioiri,
T. Tetrahedron Lett. 1993, 34, 6559. Barbero, A.; Cuadrado, P.;
Fleming, I.; Gonzalez, A. M; Pulido, F. J. J. Chem. Soc., Chem.
Commun. 1992, 351. For carbometallation of enynes see: Uenishi,
J.-I.; Kawahama, R.; Tanio, A.; Wakabayashi, S. J. Chem. Soc.,
Chem. Commun. 1993, 1438. For stannylmetallation of alkynes
see: Hibino, J.-I.; Matsubara, S.; Morizawa, Y.; Oshima, K.;
Nozaki, H. Tetrahedron Lett. 1984, 25, 2151. Barbero, A.;
Cuadrado, P.; Fleming, I.; Gonzales, A. M.; Pulido, F. J.; Rubio,
Scheme 3
When the homologous enyne 11 was treated under the same conditions,
stannyl derivative 12 was obtained as the only isomer in 73% yield
(methanol addition) and 78% yield (water addition). In the case of water
addition starting material 11 was recovered in 15% yield.

October 1998
SYNLETT
1131
R. J. Chem. Soc., Perkin Trans I 1993, 1657. Beaudet, I.; Launay,
V.; Parrain, J.-L.; Quintard, J.-P. Tetrahedron Lett. 1995, 36, 389.
solution was stirred at -40°C until was obtained of a yellow
solution and cooled to -78°C. Then water (280 µL, 15.6 mmol, 10
equiv.) was added and the the yellow solution turn to a red gel.
The temperature was allowed to warm to -40°C for 15 min, until
obtention of a red solution. The red solution was cooled to -78°C
before the addition via cannula of alkyne 6 (110 mg, 1.56 mmol)
in solution in THF (3 mL). The mixture was allowed to warm to
the appropriate temperature and when the starting material had
been consumed, the mixture was quenched by addition of brine.
The aqueous phase was extracted with diethyl ether. The
combined organic extracts were washed with brine, dried over
(
3) Zhang, H. X.; Guibé, F.; Balavoine, G. J. Org. Chem. 1990, 55,
1
857. Trost, B. M.; Li, C.-J. Synthesis 1994, 1267. Ichinose, Y.;
Oda, H.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1987, 60,
468. Kikukawa, K.; Umekawa, H.; Wada, F.; Matsuda, T. Chem.
3
Lett. 1988, 881. Zhang, H. X.; Cochran, J. C.; Bronk, B. S.;
Terrence, K. M.; Phillips, H. K. Tetrahedron Lett. 1990, 31, 6621.
Rossi, R.; Carpita, A.; Cossi, P. Synth. Commun. 1993, 23, 143.
For trans hydrostannylation of alkynes, see also: Asao, N.; Liu, J.-
X.; Sudoh, T.; Yamamoto, Y. J. Chem. Soc., Chem. Commun.
MgSO , filtered and concentrated in vacuo. The crude product
1995, 2405. For silastannylation see: Hada, M.; Tanaka, Y.; Ito,
4
was purified by flash chromatography on basic silica gel (diethyl
ether/petroleum ether 0:100 to 50:50) to give compounds 8 (460
mg, 82% yield) and 9 (91 mg, 16% yield). Compounds 1-10 are
described in ref 10.
M.; Murakami, M.; Amii, H.; Ito, Y.; Nakatsuji, H. J. Am. Chem.
Soc. 1994, 116, 8754.
(
4) Betzer, J.-F.; Ardisson, J.; Lallemand, J.-Y.; Pancrazi, A.
Tetrahedron Lett. 1997, 38, 2279.
(
16) For silylcupration of alkynes see : Fleming, I.; Newton, T. W.;
Roessler, F. J. Chem. Soc., Perkin Trans. I 1981, 2527. Fleming, I.;
Roessler, F. J. Chem. Soc., Chem. Commun. 1980, 276.
(
5) Piers, E.; Morton, H. E. J. Org. Chem. 1980, 45, 4263. Piers, E.;
Chong, J. M.; Morton, H. E. Tetrahedron Lett. 1981, 22, 4905.
Piers, E.; Chong, J. M. J. Chem. Soc., Chem. Commun. 1983, 934.
Piers, E.; Chong, J. M.; Keay, B. A. Tetrahedron Lett. 1985, 26,
(
(
17) Taylor, R. J. K. "Organocopper Reagents : a practical approach"
6265. Piers, E.; Chong, J. M. Can. J. Chem. 1988, 66, 1425. Piers,
Oxford University Press 1994. See also ref 16
E.; Chong, J. M.; Morton, H. E. Tetrahedron. 1989, 45, 363. Piers,
E.; Wong, T.; Ellis, K. A. Can. J. Chem. 1992, 70, 2058.
18) 13: To a suspension of CuCN (215 mg, 2.4 mmol, 2.5 equiv.) in
dry THF (1 mL) was added via syringe the red solution of
(
6) Thermodynamic and kinetic products in stannylcupration of
alkyne correspond to the stannylvinyl cuprate intermediates, see
ref 5 and 8. In this paper the corresponding hydrolyzed products
are also named thermodynamic and kinetic for greater
convenience.
16
dimethyl(phenyl)silyl lithium (0.6M solution in dry THF, 8.8
mL, 5.3 mmol, 5.5 equiv.) at -50°C. The suspension was stirred
for 45 min at 0°C until a purple solution was obtained and cooled
to -50°C. Then water (120 µL, 6.7 mmol, 7 equiv.) was added.
The temperature was allowed to warm to between -20°C and
(7) Piers, E.; Morton, H. E.; Chong, J. M. Can. J. Chem. 1987, 65, 78.
-10°C for 10 min until the solution became deep-red. The deep-
(
8) Singer, R. D.; Hutzinger, M. W.; Oehlschlager, A. C. J. Org.
Chem. 1991, 56, 4933. See also: Cummins, C. H.; Gordon, E. J.
Tetrahedron Lett. 1994, 35, 8133.
red solution was cooled to -50°C before addition via cannula of
enyne 1 (105 mg, 0.94 mmol) in dry THF (3 mL). The mixture
was allowed to warm to -10°C and after the starting material had
been consumed, the mixture was quenched by addition of brine.
The aqueous phase was extracted with diethyl ether. The
combined organic extracts were washed with brine, dried over
(
(
(
9) Aksela, R.; Oehlschlager, A. C. Tetrahedron 1991, 47, 1163. Still,
W. C. J. Am. Chem. Soc. 1977, 99, 4836.
10) Betzer, J.-F.; Delaloge, F.; Muller, B.; Pancrazi, A.; Prunet. J. J.
Org. Chem. 1997, 62, 7768.
MgSO , filtered and concentrated in vacuo. The crude product
4
was purified by flash chromatography on silica gel (diethyl ether/
petroleum ether 0:100 to 50:50) to give compound 13 (222 mg,
11) Addition of MeOH, phenol and water was reported in the case of
PhMe SiBEt Li addition to alkyne by: Nozaki, K.; Wakamatsu,
2
3
9
1
7
6
1
0
4% yield).
K.; Nanaka, T.; Tückmantel, W.; Oshima, K.; Utimoto, K.
Tetrahedron Lett. 1986, 27, 2007.
1
3: H NMR (200 MHz, CDCl ) δ 7.61-7.52 (m, 2H, H-arom),
.44-7.33 (m, 3H, H-arom), 6.24 (s, 1H, H-4), 5.60 (tq, 1H, J =
.7, 1.6 Hz, H-2), 4.29 (d, 2H, J = 6.7 Hz, H -1), 2.09 (s, 1H, OH),
.89 (d, 3H, J = 1.6 Hz, CH , CH -3), 1.84 (s, 3H, CH , H -6),
3
(
12) For germylation of alkynes using a proton source, see: Oda, H.;
2
Morizawa, Y.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1984, 25,
3
13
3
3
3
3217.
.41 (s, 6H, 2CH , Me Si). C NMR (50 MHz, CDCl ) δ 142.1
3
2
3
(
(
13) Cox, S.D.; Wudl, F. Organometallics 1983, 2, 184.
(C-2 or C-4), 138.1 (C-arom), 136.0 (C-3 or C-5), 135.7 (C-3 or
C-5), 133.9 (C-arom), 129.0 (C-arom), 128.9 (C-2 or C-4), 127.7
14) The use of water as proton source was first evoked by Oshima K.;
see ref 11 and 12.
(
C-arom), 59.1 (C-1), 17.0 (CH , CH -3 or CH , C-6), 16.6 (CH ,
3 3 3 3
CH -3 or CH , C-6), -3.5 (2CH , Me Si).
3
3
3
2
(
1
15) Typical procedure, Table entry 7: To a solution of
hexabutylditin (7.2 g, 12.5 mmol, 8.0 equiv.) in dry THF (20 mL)
was added n-BuLi (1.6M solution in hexane, 7.8 mL, 12.5 mmol,
(19) In some cases, stannylcupration of alkyne functions led to
formation of bis-stannyl derivatives: see ref 8, 10 and Zweifel, G.;
Leong, W. J. Am. Chem. Soc. 1987, 109, 6409. Oxidative coupling
reaction could also take place, see: Corey, E. J.;
Katzenellenbogen, J. A. J. Am. Chem. Soc. 1969, 91, 1851.
8
.0 equiv.) at -78°C. The solution was stirred for 30 min at -40°C.
Then the mixture was added via cannula to a suspension of CuCN
560 mg, 6.2 mmol, 4.0 equiv.) in dry THF (2 mL) at -78°C. The
(