Palladium-catalyzed regio- and stereoselective hydrosilylation of electron-deficient alkynes

Article abstract of DOI:10.1021/ol300279c

Highly regio- and stereoselective hydrosilylation applicable to a broad range of electron-deficient alkynes has been established using palladium catalysis. The synthetic utility of the method has been demonstrated by further transformations of α-silylalke

Full text of DOI:10.1021/ol300279c

ORGANIC
LETTERS
2012
Vol. 14, No. 6
1552–1555
Palladium-Catalyzed Regio- and
Stereoselective Hydrosilylation of
Electron-Deficient Alkynes
Yuto Sumida,* Tomoe Kato, Suguru Yoshida, and Takamitsu Hosoya*
Laboratory of Chemical Biology, Graduate School of Biomedical Science,
Institute of Biomaterials and Bioengineerings, Tokyo Medical and Dental University,
2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
sumida.cb@tmd.ac.jp; thosoya.cb@tmd.ac.jp
Received February 4, 2012
ABSTRACT
Highly regio- and stereoselective hydrosilylation applicable to a broad range of electron-deficient alkynes has been established using palladium
catalysis. The synthetic utility of the method has been demonstrated by further transformations of R-silylalkenes, particularly Hiyama coupling
and stereoinverting iododesilylation followed by SuzukiÀMiyaura coupling, which enables stereodivergent syntheses of R-arylenoates.
Silylalkenes serve as a powerful building block in or-
ganic synthesis owing to diverse types of valuable transfor-
mations, such as protodesilylation providing the corre-
sponding alkene, TamaoÀFleming oxidation producing
the carbonyl compound, and Hiyama coupling enabling
new carbonÀcarbon bond formations.1 Silylalkene also
offers advantages over other metal alkenes in terms of
stability, cost, andlow toxicity. Althoughtransition-metal-
catalyzed hydrosilylation of alkynes is one of the most
straightforward and popular methods of preparing silyl-
alkenes,2 it often results in regio- and/or stereoisomeric
mixtures that are usually difficult to separate. To address
this, enormous efforts have been made to regulate the
regio- and stereochemistry, particularly for the reaction
of internal alkynes. Accordingly, some successful methods
have been developed, including systems employing cation-
ic ruthenium3 and platinum4 catalyses as well as a smart
approach using a well-designed substrate appended with a
regioregulatory metal-coordinating group.5 Despite these
outstanding studies, however, establishing a method capa-
ble of providing a specific isomer with a broader substrate
scope remains a challenge. Here we describe highly regio-
and stereoselective hydrosilylation achieved by the use of
palladium catalysis,6 generally applicable to alkynes acti-
vated by an adjacent electron-withdrawing group, as well
(3) (a) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2001, 123, 12726–
€
12727. (b) Trost, B. M.; Ball, Z. T.; Joge, T. Angew. Chem., Int. Ed. 2003,
42, 3415–3418. (c) Trost, B. M.; Ball, Z. T.; Laemmerhold, K. M. J. Am.
Chem. Soc. 2005, 127, 10028–10038. (d) Trost, B. M.; Ball, Z. T. J. Am.
Chem. Soc. 2005, 127, 17644–17655.
(4) (a) Rooke, D. A.; Ferreira, E. M. J. Am. Chem. Soc. 2010, 132,
11926–11928. (b) After submission of this paper, Pt-catalyzed hydro-
silylation of internal alkynes including ynoates was reported: Rooke,
D. A.; Ferreira, E. M. Angew. Chem., Int. Ed. 2012, DOI: 10.1002/
anie.201108714.
(1) (a) Brook, M. A. Silicon in Organic, Organometallic and Polymer
Chemistry, Wiley: New York, 2000. (b) Trost, B. M.; Ball, Z. T. Synthesis
2005, 853–887.
(5) Kawasaki, Y.; Ishikawa, Y.; Igawa, K.; Tomooka, K. J. Am.
Chem. Soc. 2011, 133, 20712–20715.
(6) For Pd-catalyzed hydrostannylation of electron-deficient
alkynes, see: (a) Cochran, J. C.; Bronk, B. S.; Terrence, K. M.; Phillips,
(2) (a) Ojima, I. In The Chemistry of Organic Silicon Compounds;
Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, UK, 1989; Vol. 1, Chapter 25.
(b) Hiyama, T.; Kusumoto, T. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 8,
Chapter 3.12. (c) Comprehensive Handbook on Hydrosilylation; Marci-
niec, B., Ed.; Pergamon Press: Oxford, 1992. (d) Marciniec, B.; Maciejewski,
H.; Pietraszuk, C.; Pawluc, P. In Hydrosilylation: A Comprehensive Review
on Recent Advances; Marciniec, B., Ed.; Advances in Silicon Science;
Springer: Berlin, 2009; Vol. 1, Chapters 2 and 3.
ꢀ
H. K. Tetrahedron Lett. 1990, 31, 6621–6624. (b) Zhang, H. X.; Guibe,
F.; Balavoine, G. J. Org. Chem. 1990, 55, 1857–1867. (c) Rossi, R.;
Carpita, A.; Cossi, P. Tetrahedron Lett. 1992, 33, 4495–4498. (d)
ꢀ
Dodero, V. I.; Koll, L. C.; Faraoni, M. B.; Mitchell, T. N.; Podesta,
ꢀ
J. C. J. Org. Chem. 2003, 68, 10087–10091.
r
10.1021/ol300279c
Published on Web 02/23/2012
2012 American Chemical Society

as some practical derivatizations of the hydrosilylated
products.
The optimized conditions were commonly applicable to
various hydrosilanes, with a few exceptions. Most tri-
alkylsilanes tested in the reaction with ynoate 1a similarly
afforded the desired adduct in excellent yield and selectiv-
ities (Table 2, entries 1À3), whereas the highly sterically
hindered silane showed poor reactivity (entry 4). Chlor-
ohydrosilane tended to deactivate the palladium catalyst,
leaving the alkyne intact (entry 5). Silanes substituted with
2-pyridyl or alkoxy groups, the products of which are
expected to be readily transformable (vide infra), reacted
more rapidly (entries 6À8). Among the dihydrosilanes
examined, t-Bu2SiH2 afforded a monohydrosilylated pro-
duct in high yield without forming an over-reacted product
(entry 10).
Initially, we explored the optimized conditions for E-R-
selective hydrosilylation of methyl 2-hexynoate (1a) with
PhMe2SiH (2a) (1.2 equiv). The reaction in toluene at room
temperature using PtCl2 (5 mol %), the effective cat-
alyst reported for E-R-selective hydrosilylation of alkynyl
ketones,4 proceeded with high efficiency but in diminished
regioselectivity (Table 1, entry 1). Adding a phosphine
ligand to this system was rather detrimental to the reaction
rate (entry 2). Other widely used catalysts, such as the
Speier, Karstedt, and Wilkinson catalysts, also gave un-
satisfying results (entries 3À5). The reaction with a cationic
ruthenium catalyst afforded (Z)-β-isomer (Z)-4a selec-
tively, as reported (entry 6).3 After extensive screening, we
found that a palladium(0) catalyst, particularly the combi-
nation of Pd(dba)2 and PCy3,7,8 worked ideally, providing
the desired (E)-R-isomer (E)-3a in an excellent yield with
extremely high regio- and stereoselectivity (entry 7).9 When
PhMe2SiD (2a-D, >99% D)10 was used instead of 2a, deu-
terium was introduced completely and exclusively to the
β-position of the product. This result indicates that the re-
action proceeds in accordance with the ChalkÀHarrod
mechanism, which involves oxidative addition of silane
to Pd(0), regio- and stereoselective hydropalladation to
the alkyne, and then reductive elimination to afford the
product.11
Table 2. Scope of Hydrosilanes
entry
Si-H
time (h)
product
yield (%)a
1
BnMe2SiH (2b)
Et3SiH (2c)
14
14
14
48
2
3b
3c
3d
3e
3f
99
2
86
3
t-BuMe2SiH (2d)
i-Pr3SiH (2e)
99
4b
5
(27)c
0
t-Bu2ClSiH (2f)
2-PyMe2SiH (2g)
(MeO)2MeSiH (2h)
(EtO)3SiH (2i)
PhMeSiH2 (2j)
t-Bu2SiH2 (2k)
Table 1. Optimization toward E-R-Selective Hydrosilylation of
R,β-Ynoate
6
14
3
3g
3h
3i
76
7
90
8
1
73 (95)c
CM
85
9
2
3j
10
2
3k
a Isolated yields; R/β=>99:1;E/Z= >99:1. CM = complex mixture.
b Reaction conducted at 80 °C. c 1H NMR yields in parentheses.
A broad substrate scope of alkynes was represented, as
well (Table 3). Not only β-alkylated ynoates but also
β-aryl- and trimethylsilyl-substituted compounds performed
well as substrates (entries 1À4). A siloxymethyl group,
which could give a low selectivity because of the electronic
effect, did not interfere with the regioselectivity, in sharp
contrast with the platinum catalytic system (entry 5).4
A substrate without a β-substituent as well as one having
another terminal alkynyl group could also be employed,
although the isolated yields of these products were mod-
erate on account of their instability (entries 6 and 7).
Moreover, our system was widely applicable to alkynes
activated by other electron-withdrawing groups including
ynones, ynal, and ynamide (entries 8À11). Alkynyl sulfone
also acted as a good substrate, although the product was
hard to isolate because protodesilylation occurred easily
during purification on silica gel (entry 12). Unfortunately,
entry
catalyst
yield (%)a
ratio of 3a/4aa
1
PtCl2
87
8c
82/18
ND
2b
3
PtCl2/PCy3
H2PtCl6 4H2O
89
83/17
79/21
44/56
2/98e
>99/1
3
4
Pt(dvds)
27
5
RhCl(PPh3)3
15
6d
7b
[Cp*Ru(MeCN)3]PF6
Pd(dba)2/PCy3
96
96 (90)f
a Combined yields and ratio of hydrosilylated products determined
by 1H NMR. In terms of stereochemistry, unless otherwise noted,
(E)-isomer (E/Z = >99:1) was obtained. ND = not determined.
b Phosphine (10 mol %) was used. c Unreacted 1a (87%) remained.
d Reaction performed using 3 mol % of the catalyst in acetone for 2 h.
e The E/Z ratio of β-isomer was 6/94. f Isolated yield in parentheses.
(7) Pd2(dba)3/PCy3-catalyzed hydrosilylation of terminal alkynes:
Motoda, D.; Shinokubo, H.; Oshima, K. Synlett 2002, 1529–1531.
(8) Other electron-rich ligands such as P(n-Bu)3, P(c-C5H9)3, and
IMes HCl were also effective. See Supporting Information for details.
(11) (a) Chalk, A. J.; Harrod, J. F. J. Am. Chem. Soc. 1965, 87, 16–21.
(b) Harrod, J. F.; Chalk, A. J. J. Am. Chem. Soc. 1965, 87, 1133–1135. (c)
Hayashi, T.; Hirate, S.; Kitayama, K.; Tsuji, H.; Torii, A.; Uozumi, Y. J.
Org. Chem. 2001, 66, 1441–1449.
3
(9) See Supporting Information for characterization of the isomers.
(10) PhMe2SiD (2a-D) was prepared according to: Caseri, W.;
Pregosin, P. S. J. Organomet. Chem. 1988, 356, 259–269.
Org. Lett., Vol. 14, No. 6, 2012
1553

the reaction of dimethyl acetylene dicarboxylate, which
has an extra electron-withdrawing group, resulted in a
complex mixture even though the reaction was carried out
at 0 °C.12
As we attempted to prepare silylalkenes in larger amounts,
we encountered a problem: low reproducibility in stereo-
selectivity of the product was observed in certain cases.13
After careful studies, we found that silylalkene (E)-3i could
be partially isomerized by treatment with triethoxysilane (2i)
under the same conditions as those used for hydrosilylation
of alkynes.14 This result suggests that the undesired isomer-
ization is triggered by the second hydrosilylation of initially
formed silylalkene with redundant hydrosilane, followed by
β-hydride elimination (Scheme 1).15 On the basis of this
observation, we succeeded in preparing a sufficient amount
of stereoisomerically pure silylalkenes with high reproduc-
ibility, merely by using an equimolar amount of hydrosilane.
Table 3. Scope of Electron-Deficient Alkynes
Scheme 1. Plausible Mechanism for Partial Isomerization of
Silylalkene via Second Hydrosilylation
Silylalkenes were demonstrated to be capable of conver-
sion to alkene derivatives by forming a new CÀH or CÀC
bond with a high degree of stereochemical retention. For
example, ethyl cis-cinnamate (5) was obtained efficiently
from (E)-R-silylalkene (E)-3n by protodesilylation using
TBAF in water-containing THF (Figure 1, eq 1). Moreover,
after the conditions were fine-tuned, Hiyama coupling16 was
accomplished under mild conditions without decreasing the
E/Z ratio: adding (E)-3n slowly to a mixture of 4-iodoani-
sole, PdCl2(PPh3)2, AgF,17 and K2CO3 in MeCN afforded
R-arylated cinnamate (Z)-6 in high yield (eq 2). To our
knowledge, this is the first example of Hiyama coupling at
the R-position of R,β-unsaturated carbonyl compounds. The
dimethoxysilyl group worked as well as the triethoxysilyl
(13) Low reproducibility was also observed in 0.25 mmol scale. The
reactions of ynoate 1a (0.25À5 mmol) with 1.2 equiv of 2i under the
optimized conditions always gave the product in high yields (>90% by
1H NMR), but the E/Z ratio randomly oscillated between 64/36 and
>99/1. Partial isomerization was frequently observed particularly when
electron-deficient hydrosilane was used and/or the hydrosilylated pro-
duct was highly reactive, such as triethoxysilylalkenyl sulfone 3w.
(14) No isomerization of (E)-3i was observed when any one of the
reagents among Pd(dba)2, PCy3, or triethoxysilane was absent.
(15) (a) Mori, A.; Takahisa, E.; Kajiro, H.; Nishihara, Y.; Hiyama,
T. Polyhedron 2000, 19, 567–568. (b) Mori, A.; Takahisa, E.; Yamamura,
Y.; Kato, T.; Mudalige, A. P.; Kajiro, H.; Hirabayashi, K.; Nishihara, Y.;
Hiyama, T. Organometallics 2004, 23, 1755–1765.
a Isolated yields unless otherwise noted; R/β = >99:1; E/Z =
>99:1. b Reaction performed with 5 mmol of 1d using Pd(OAc)2 instead
of Pd(dba)2. c Product contained a small amount of protodesilylated
product. d Yields determined by 1H NMR in parentheses. e Isolated yield
after derivatization to the corresponding allyl alcohol by Luche reduc-
tion. f 1.0 equiv of 2i was used.
(16) (a) Hiyama, T. In Metal Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998;
Chapter 10. (b) Denmark, S. E.; Sweis, R. F. In Metal Catalyzed Cross-
Coupling Reactions; 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-
VCH: Weinheim, Germany, 2004; Chapter 4.
(12) The reaction of 1-phenyl-1-propyne, an unactivated alkyne, with
triethoxysilane (2i) afforded the product in poor regioselectivity (66%
yield, R/β = 74/26, determined by 1H NMR).
(17) Using AgF as a FÀ source was crucial. All attempts to use TBAF,
which is generally used in Hiyama coupling, under various palladium/
phosphine ligand systems were unsuccessful.
1554
Org. Lett., Vol. 14, No. 6, 2012

group: the alkene (E)-3h was successfully coupled with an
electron-deficient aryl iodide, 1-iodo-2-nitrobenzene, fur-
nishing the desired product (Z)-7, which was reported to
be readily convertible to indole derivatives (eq 3).18 In addi-
tion, the coupling reaction of silylalkene (E)-3i with phenyl
acetylene also proceeded smoothly under almost the same
conditions providing eneyne (Z)-8 efficiently (eq 4).19
Scheme 2. Stereodivergent Syntheses of R-Arylenoates from the
Same R-Silylenoate
mechanism is unclear, the characteristics of the triethox-
ysilyl group are presumed to contribute greatly to the high
levels of stereoinversion.21 Stereoinverted R-iodoenoate
served as a good substrate in SuzukiÀMiyaura coupling:
Pd/SPhos22-catalyzed reaction of (Z)-9 with p-anisylbo-
ronic acid afforded (E)-R-arylenoate (E)-11 stereospecifically.
Meanwhile, as described above, the counterpart (Z)-isomer
(Z)-11 could be obtained directly by Hiyama coupling of
silylalkene (E)-3i with 4-iodoanisole. Considering that both
(E)-11 and (Z)-11 originate from the same starting material,
this approach offers a rational method of preparing both
stereoisomers of an R-arylenoate expeditiously.
In summary, we found an efficient palladium catalytic
system for highly regio- and stereoselective hydrosilylation
applicable to a broad range of electron-deficient alkynes
and hydrosilanes. Highly stereocontrolled transforma-
tions of the hydrosilylated products clearly demonstrated
the utility of the method. Specifically, Pd-catalyzed cou-
pling reactions in combination with stereoinverting iodo-
desilylation of silylalkene offers a great advantage in
preparing both stereoisomers of R-substituted R,β-unsatu-
rated carbonyl compounds.
Figure 1. Stereoretaining transformations of silylalkenes.
Gratifyingly, the stereodivergentsyntheses ofR-aryleno-
ates were achieved with the aid of iododesilylation of
R-silylenoate, providing R-iodoenoate, the geometry of
which is almost completely inverted. Thus, treating (E)-3i
with 2.0 equiv of ICl (1.0 M solution in CH2Cl2), which is
the general condition previously reported for stereoconver-
gent iododesilylation of R-trimethylsilylenones,20 afforded
the desired product (Z)-9 with inverted geometry and high
stereoselectivity (E/Z = 3/97) (Scheme 2). When only an
equimolar amount of ICl was employed at a lower tem-
perature, iodochlorinated ester 10 was unexpectedly ob-
tained as a single diastereomer, along with a small amount
of (E)-9. Compound 10 was more stable than anticipated
and, by treating with TBAF at À78 °C, could also be
converted into (Z)-9 also in a highly regiocontrolled man-
ner. This result indicates that 10is a possible intermediateof
the stereoinverting iododesilylation. Although the precise
Acknowledgment. The authors thank Dr. Hiroyuki
Masuno and Ms. Ayako Hosoya at Tokyo Medical and
Dental University for HRMS analyses.
€
(18) Soderberg, B. C. G.; Banini, S. R.; Turner, M. R.; Minter, A. R.;
Arrington, A. K. Synthesis 2008, 903–912.
(19) For Pd-catalyzed cross-coupling of ArSi(OMe)3 with terminal
alkyne in the presence of AgF and base, see: Ye, Z.; Liu, M.; Lin, B.; Wu,
H.; Ding, J.; Cheng, J. Tetrahedron Lett. 2009, 50, 530–532.
(20) Alimardanov, A.; Negishi, E.-i. Tetrahedron Lett. 1999, 40,
3839–3842.
(21) When R-triethylsilylenoate 3c was treated with 2.0 equiv of ICl,
the R-iodoenoate was obtained as a mixture of stereoisomers (E/Z = 40/
60) in 98% yield (1H NMR).
Supporting Information Available. Experimental pro-
cedures and characterization data, including copies of
1H and 13C NMR spectra, are provided. This material
is available free of charge via the Internet at http://
pubs.acs.org.
(22) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461–1473.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 6, 2012
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