Reduction of alkynes into 1,2-dideuterioalkenes with hexamethyldisilane and deuterium oxide in the presence of a palladium catalyst

Article abstract of DOI:10.1039/b512245g

A combination of hexamethyldisilane and deuterium oxide was found to work as a deuterium transfer reagent for alkynes in the presence of a catalytic amount of a palladium complex to give (E)-1,2-dideuterioalkenes selectively through the corresponding (Z)-isomer. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b512245g

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Reduction of alkynes into 1,2-dideuterioalkenes with
hexamethyldisilane and deuterium oxide in the presence of a palladium
catalyst{
Eiji Shirakawa,* Hidehito Otsuka and Tamio Hayashi*
Received (in Cambridge, UK) 5th September 2005, Accepted 5th October 2005
First published as an Advance Article on the web 2nd November 2005
DOI: 10.1039/b512245g
A combination of hexamethyldisilane and deuterium oxide was
found to work as a deuterium transfer reagent for alkynes in
the presence of a catalytic amount of a palladium complex to
give (E)-1,2-dideuterioalkenes selectively through the corre-
(1)
sponding (Z)-isomer.
Alkenes deuterated at their olefinic protons are an important class
of compounds, which can be utilized for biological research and
the elucidation of reaction mechanisms. Several efforts have been
devoted to the development of the reduction of alkynes into 1,2-
deuterioalkenes with deuterium oxide, which is undoubtedly the
most inexpensive and easy to handle deuterium source. Most of
the previously reported methods, however, have failed to reconcile
Table 1 Palladium-catalyzed reduction of alkynes into alkenesa
a high deuteration ratio with high stereoselectivity.1,2 On the other
hand, combinations of a hydrosilane and a protic compound
(ROH) in the presence of a palladium catalyst have been used for
transfer hydrogenation of alkynes.3 However, both reagents have
to be deuterated as D–Si and ROD to apply this method to the
deuteration.4 No report has been available that disilanes instead of
hydrosilanes work as reductants of alkynes, in spite that only deu-
terated proton sources are required there for deuteration. Here we
report the palladium-catalyzed reduction of alkynes with hexa-
methyldisilane and deuterium oxide, which gives (E)-1,2-dideuter-
ioalkenes selectively through the corresponding (Z)-derivatives.
Treatment of diphenylacetylene (1a) with hexamethyldisilane (2:
1.5 equiv.), D2O (10 equiv.), [PdCl(g3-C3H5)]2 (5 mol% of Pd) and
PPh3 (10 mol%) in DMA at 80 uC for 24 h gave 99% yield of
(E)-stilbene-d2 (3a) in 99.1% deuterium ratio with high stereo-
selectivity (99.2% E) (eqn (1) and entry 1 in Table 1).5 Even a trace
amount of an overreduced product, 1,2-diphenyl-1,1,2,2-tetradeu-
terioethane, was not detected in the reaction mixture. DMSO as a
solvent showed comparable efficiency to DMA, whereas less polar
solvents such as 1,4-dioxane and toluene were totally ineffective.
The corresponding transfer hydrogenation using H2O (2.5 equiv.)
instead of D2O gave hydrogenation product 4a, (E)-stilbene, in
98% yield.
Yield (%)b
of 3
Yield (%)b,c
of 4
Entry R1
R2
Ph
1
2
3
4
5
6
7
8
9
10
a
Ph
99
98d
91
—
—
—
—
96
95
—
—
4-CF3C6H4
4-CF3C6H4
4-MeOCOC6H4 Ph
4-MeOC6H4
4-MeC6H4
4-MeOC6H4
2-MeC6H4
Ph
4-CF3C6H4 94
Ph
93
93
99
96
Ph
Ph
4-CF3C6H4 85
2-MeC6H4
t-Bu
88
79
64
4-n-C5H11C6H4 Me
The reaction was carried out in DMA (0.5 mL) at 80 uC for 24 h
using an alkyne (0.40 mmol), Me3SiSiMe3 (0.60 mmol) and D2O
(4.0 mmol) in the presence of [PdCl(g3-C3H5)]2 (10 mmol) and PPh3
b
c
(40 mmol). Isolated yield based on the alkyne. H2O (1.0 mmol)
was used instead of D2O. Reaction time 5 3 h.
d
Alkyl(aryl)acetylenes also participated in the deuteration (entries 9
and 10). The hydrogen transfer reaction from H2O to some of the
alkynes was conducted successfully (entries 1, 2, 7 and 8).
(E)-Isomers were found to be produced by isomerization of the
initially formed (Z)-isomers. Thus, the reaction of diphenylacety-
lene (1a) with Me3SiSiMe3 (1.5 equiv.) and H2O (2.5 equiv.) in the
presence of [PdCl(g3-C3H5)]2–PPh3 (5 mol% of Pd, PPh3/Pd 5 2)
at 80 uC for 30 min gave the (Z)-isomer predominantly (E : Z 5
14 : 86) with 37% conversion, and heating the reaction mixture for
another 2.5 h at 80 uC changed the E : Z ratio to .99 : 1 with full
conversion of 1a (eqn (2)).
The deuteration with Me3SiSiMe3–D2O was applied to various
symmetrical and unsymmetrical internal alkynes, giving high yields
of (E)-1,2-dideuterioalkenes with .97% deuterium ratios and
.98% (E)-selectivities (Table 1). In addition to diphenylacetylene,
those having one or two electron-withdrawing and/or -donating
substituents accepted the addition of deuterium atoms (entries 2–8).
Department of Chemistry, Graduate School of Science, Kyoto
University, Sakyo, Kyoto 606-8502, Japan.
E-mail: shirakawa@kuchem.kyoto-u.ac.jp; Fax: 81 75 753 3988
{ Electronic supplementary information (ESI) available: experimental
details. See DOI: 10.1039/b512245g
ð2Þ
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 5885–5886 | 5885

View Article Online
As described so far, [PdCl(g3-C3H5)]2–PPh3 is an effective
catalyst for the reduction of alkynes. In contrast, the present
reaction was not catalyzed by Pd(PPh3)4 or Pd(PPh3)2 generated
from PdCp(g3-C3H5) and PPh3 (1 : 2). However, addition of HCl
to the PdCp(g3-C3H5)–PPh3 system activated the catalyst and the
hydrogenation was completed within 1 h. From these observa-
tions, a combination of a palladium(0) complex and HCl seems to
be important, giving
a
species like H–Pd–Cl.6 Actually,
PdH(Cl)(PPh3)2 was found to be as effective as [PdCl(g3-
C3H5)]2–PPh3 as a catalyst for the reduction. The high activity
of the H–Pd–Cl species was found to be ascribed to the ability to
cleave Si–Si bonds.7 Thus, 85% of hexamethyldisilane (2) was
converted to hexamethyldisiloxane (5) on treatment with [PdCl(g3-
C3H5)]2–PPh3 and H2O at 80 uC for 3 h in the absence of an
alkyne, whereas PdCp(g3-C3H5)–PPh3 did not catalyze the
reaction at all (eqn (3)). A plausible catalytic cycle of the cleavage
of the Si–Si bond is shown in Scheme 1. s-Bond metathesis
between H–Pd–Cl and disilane 2 cleaves the Si–Si bond to give
Me3SiCl and H–Pd–SiMe3 6. Reductive elimination from 6 gives
Me3SiH and a palladium(0) complex. Then oxidative addition of
HCl, generated by the reaction of Me3SiCl with H2O, to the
palladium(0) complex regenerates H–Pd–Cl. Me3SiH generated
here should undergo the dehydrogenative coupling with H2O in
the absence of an alkyne to give Me3SiOH,8 which is dehydrated
into 5 (eqn (4)).
Scheme 2
H–Pd–Cl complex, and the following b-hydride elimination gives
the thermodynamically more stable (E)-isomer.9
In conclusion, we have disclosed that (E)-1,2-dideuterioalkenes
are selectively obtained from alkynes using the most inexpensive
deuterium source, D2O, and hexamethyldisilane with the aid of a
palladium catalyst.
Notes and references
1 For examples, see: E. M. Richards, J. C. Tebby, R. S. Ward and
D. H. Williams, J. Chem. Soc. C, 1969, 1542–1544; Y. Kataoka, K. Takai,
K. Oshima and K. Utimoto, J. Org. Chem., 1992, 57, 1615–1618;
M. A. G. M. Tinga, G. Schat, O. S. Akkerman, F. Bickelhaupt, E. Horn,
H. Kooijman, W. J. J. Smeets and A. L. Spek, J. Am. Chem. Soc., 1993,
115, 2808–2817; K. Harada, H. Urabe and F. Sato, Tetrahedron Lett.,
1995, 36, 3203–3206; T. Nishikawa, H. Shinokubo and K. Oshima,
Tetrahedron, 2003, 59, 9661–9668.
2 Deuterium sources other than D2O have been used. D2 with the Lindlar
catalyst: W. M. Kwok, C. Ma, D. Phillips, A. Beeby, T. B. Marder,
´
R. LI. Thomas, C. Tschuschke, G. Baranovic, P. Matousek, M. Towrie
ð3Þ
and A. W. Parker, J. Raman Spectrosc., 2003, 34, 886–891. ND3 in the
Birch reduction: S. H. Courtney, M. W. Balk, L. A. Philips, S. P. Webb,
D. Yang, D. H. Levy and G. R. Fleming, J. Chem. Phys., 1988, 89,
6697–6707.
3 (a) B. M. Trost and R. Braslau, Tetrahedron Lett., 1989, 30, 4657–4660;
(b) H. Sakurai, J. Abe and K. Sakamoto, Main Group Met. Chem., 1990,
13, 203–209; (c) For a review, see: F. Sato, in Handbook of
Organopalladium Chemistry for Organic Synthesis, ed. E. Negishi,
Wiley, New York, 2002, pp. 2759–2765.
4 A Ph2SiD2–MeOD system was reported to transform diphenylacetylene
into (Z)-stilbene-d2 in 89% deuterium ratio. See reference 3b.
1
5 Deuterium ratio and stereoselectivity were determined by H NMR and
GC/GC-MS, respectively.
6 [PdCl(g3-C3H5)]2–PPh3 must be reduced to a palladium(0) complex by
Me3SiSiMe3, leaving Me3SiCl as a by-product, which gives Me3SiOH
(then Me3SiOSiMe3) and HCl on reaction with H2O. For the reaction of
p-allylpalladium complexes with disilanes, see: Y. Tsuji, M. Funato,
M. Ozawa, H. Ogiyama, S. Kajita and T. Kawamura, J. Org. Chem.,
1996, 61, 5779–5787. For a review, see: Y. Tsuji, in Handbook of
Organopalladium Chemistry for Organic Synthesis, ed. E. Negishi, Wiley,
New York, 2002, pp. 1913–1916.
Scheme 1
7 Yamamoto and Kumada reported that the Si–Si bonds of disilanes such
as PhMe2SiSiMe3 are cleaved by ethanol in the presence of a catalytic
amount of PdCl2(PEt3)2 to give ethoxysilanes with evolution of molecular
hydrogen. Disilanes lacking a p-substituent are inert there. K. Yamamoto,
M. Kumada, I. Nakajima, K. Maeda and N. Imaki, J. Organomet.
Chem., 1968, 13, 329–341; K. Yamamoto and M. Kumada, J. Organomet.
Chem., 1972, 35, 297–302.
8 For the palladium-catalyzed dehydrogenative coupling of hydrosilanes
with alcohols to give alkoxysilanes, see: L. H. Sommer and J. E. Lyons,
J. Am. Chem. Soc., 1967, 89, 1521–1522.
ð4Þ
With a H–Pd–Cl complex and Me3SiH in our hands, it is most
likely that the reduction of alkynes with Me3SiSiMe3–D2O follows
essentially the same catalytic cycle (Scheme 2, exemplified by the
reduction of diphenylacetylene) as proposed by Trost for the
palladium-catalyzed reduction of alkynes with a hydrosilane and
acetic acid.3a Anionic ligand X stands for OAc for Trost or Cl for
us. Initially formed (Z)-4a should insert into the H–Pd bond of the
9 R. Cramer and R. V. Lindsey, Jr., J. Am. Chem. Soc., 1966, 88,
3534–3544.
5886 | Chem. Commun., 2005, 5885–5886
This journal is ß The Royal Society of Chemistry 2005