Alkyne hydrosilylation catalyzed by a cationic ruthenium complex: Efficient and general trans addition

Article abstract of DOI:10.1021/ja0528580

The complex [Cp*Ru(MeCN)₃]PF₆ is shown to catalyze the hydrosilylation of a wide range of alkynes, Terminal alkynes afford access to α-vinylsilane products with good regioselectivity. Deuterium labeling studies indicate a clean trans

Full text of DOI:10.1021/ja0528580

Published on Web 11/19/2005
Alkyne Hydrosilylation Catalyzed by a Cationic Ruthenium
Complex: Efficient and General Trans Addition
Barry M. Trost* and Zachary T. Ball
Contribution from the Department of Chemistry, Stanford UniVersity,
Stanford, California 94305-5080
Received May 2, 2005; E-mail: bmtrost@stanford.edu
Abstract: The complex [Cp*Ru(MeCN)3]PF6 is shown to catalyze the hydrosilylation of a wide range of
alkynes. Terminal alkynes afford access to R-vinylsilane products with good regioselectivity. Deuterium
labeling studies indicate a clean trans addition process is at work. The same complex is active in internal
alkyne hydrosilylation, where absolute selectivity for the trans addition process is maintained. Several internal
alkyne substrate classes, including propargylic alcohols and R,â-alkynyl carbonyl compounds, allow
regioselective vinylsilane formation. The tolerance of a wide range of silanes is noteworthy, including alkyl-,
aryl-, alkoxy-, and halosilanes. This advantage is demonstrated in the direct synthesis of triene substrates
for silicon-tethered intramolecular Diels-Alder cycloadditions.
Metal-catalyzed simple addition reactions of alkynes are
important synthetic processes and are desirable from the
standpoint of synthetic efficiency and atom economy. Questions
of regio- and stereoselectivity become important considerations,
and pathways affording syn addition are plentiful and well-
studied. Metal catalysis of trans addition processesswhere new
bonds must be formed on opposite sides of the alkyneshave
only rarely been observed. Indeed, the possibility of creating
direct trans addition processes which do not involve initial cis
addition followed by E/Z isomerization is an exciting target.
This paper describes our work studying trans addition processes
in alkyne hydrosilylation with ruthenium catalysts to afford
vinylsilane products.
However, the utility of vinylsilanes has been inhibited by the
inconvenience of accessing stereo- and regio-defined vinylmetal
compounds. Among the possible routes to these compounds,
hydrosilylation of alkynes represents the most straightforward,
atom-economical access.6 Classical platinum catalysis7 provides
clean cis addition to (E)-vinylsilanes (2), and ligand tuning has
made this a very regioselective process as well.8 In addition,
there has been significant progress using a variety of metal-
catalyzed approaches to provide stereodefined, 1,2-substituted
vinylsilanes of the form 1 or 2. There has been no reported
general access to 1,1-disubstituted vinylsilanes9 (3), and very
little is known about selectivity in accessing trisubstituted (4,
5) vinylsilanes.10
Vinylmetal species are extremely important building blocks
in organic synthesis.1,2 Among these, vinylsilanes play a growing
role due to their low cost, low toxicity, ease of handling, and
simplicity of byproduct removal. Particularly significant is the
potential of vinylsilanes as nucleophilic partners in palladium-
catalyzed cross-coupling reactions.3 Vinylsilanes are also useful
as acceptors in conjugate addition reactions, as masked ketones
through Tamao-Fleming oxidation,4 and as terminators for
cation cyclizations.5 Unlike most other organometallic reagentss
including in many cases organoboranes and organostannaness
vinylsilanes can be readily carried through many synthetic
operations.
A large number of metal systems are effective in the
hydrosilylation of terminal alkynes to produce linear vinyl-
silanes. Some of these afford good control of olefin geometry.
The limited number of known hydrosilylations with ruthenium
(6) Hiyama, T.; Kusumoto, T. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 8, pp 763-792. Trost,
B. M.; Ball, Z. T. Synthesis 2005, in press.
(1) Ojima, I.; Li, Z.; Zhu, J. In The Chemistry of Organosilicon Compounds;
Rappoport, Z., Apeloig, Y., Eds.; John Wiley & Sons: Great Britain, 1998;
Vol. 2, pp 1687-1792.
(7) Lewis, L. N.; Sy, K. G.; Bryant, G. L.; Donahue, P. E. Organometallics
1991, 10, 3750-3759. Voronkov, M. G.; Pukhnarevich, V. B.;
Tsykhanskaya, I. I.; Ushakova, N. I.; Gaft, Y. L.; Zakharova, I. A. Inorg.
Chim. Acta 1983, 68, 103-105.
(2) Langkopf, E.; Schinzer, D. Chem. ReV. 1995, 95, 1375-1408.
(3) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845-853. Hiyama, T. In Metal-
catalyzed Cross-coupling Reactions; Diederich, F., Stang, P., Eds.; Wiley-
VCH: Weinheim, 1998. Mowery, M.; DeShong, P. Org. Lett. 1999, 1,
2137-2140. Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835-
846.
(8) Green, M.; Spencer, J. L.; Stone, F. G. A.; Tsipis, C. A. J. Chem. Soc.,
Dalton Trans. 1977, 1525-1529. Tsipis, C. A. J. Organomet. Chem. 1980,
187, 427-446. Takahashi, K.; Minami, T.; Ohara, Y.; Hiyama, T.
Tetrahedron Lett. 1993, 34, 8263-8266. Denmark, S. E.; Wang, Z. G.
Org. Lett. 2001, 3, 1073-1076.
(4) Tamao, K.; Maeda, K. Tetrahedron Lett. 1986, 27, 65-68. Jones, G. R.;
(9) For an approach see: Sharma, S.; Oehlschlager, A. C. Tetrahedron Lett.
1988, 29, 261-264.
(10) Molander, G. A.; Retsch, W. H. Organometallics 1995, 14, 4570-4575.
Landais, Y. Tetrahedron 1996, 52, 7599-7662.
(5) Blumenkopf, T. A.; Overman, L. E. Chem. ReV. 1986, 86, 857-873.
9
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10.1021/ja0528580 CCC: $30.25 © 2005 American Chemical Society

Alkyne Hydrosilylation Catalyzed by [Cp*Ru(MeCN)3]PF6
A R T I C L E S
Table 1. Optimization of Terminal Alkyne Hydrosilylationa
catalysts give the analogous linear products.11,12 Free alcohols12
and carbonyl groups13 have been shown to direct hydrosilylation
to provide internal silanes, presumably through coordination.
However, at the time this work was conducted and published,14-16
there were no reports of nondirected terminal alkyne hydro-
silylation to afford preferentially the R-vinylsilane (3),17 and
there remain no alternate hydrosilylation methods to prepare
trisubstituted (Z)-vinylsilanes (4).
Reaction Discovery, Optimization, and Markovnikov
Hydrosilylation of Terminal Alkynes
We have for some time pursued a research program targeting
the discovery of new simple addition reactions catalyzed by
cyclopentadienylruthenium complexes such as [CpRu(MeCN)3]-
PF6 (6) for the formation of C-C and C-X bonds.18 From this
general goal came the discovery that [CpRu(MeCN)3]PF6 (6)
and the related complex [Cp*Ru(MeCN)3]PF6 (7) catalyze the
hydrosilylation of alkynes (Table 1).14-16
Hydrosilylation of terminal alkynes occurs at or below room
temperature, catalyzed by the ruthenium complex 6, to afford
the 1,1-disubstituted R-vinylsilane. This finding is noteworthy
as a means of accessing R-vinylmetal species in general. Access
to R-vinylsilanes12,19,20 or to other R-metalloid species (boron,
tin, etc.) in a general and efficient manner is quite limited.20,21
Complex 6 provides generally excellent results with trialkyl-
silanes, but regioselectivity is significantly diminished when
alkoxysilanes are employed as substrates (Table 1, entry 6).
Alkoxysilanes are crucial for many important synthetic applica-
tions of vinylsilanes, and poor reactivity or selectivity upon
switching to alkoxysilane substrates plagues many extant
catalytic systems. In the case at hand, switching to the
pentamethylcyclopentadienyl analogue 7 afforded increased
selectivity (entry 9). This increased selectivity with complex 7
is general. Reaction scope and turnover numbers are very similar
for the two catalysts, and so complex 7 is the superior catalyst
for all reaction classes thus far examined.
a All reactions were performed on 0.2-0.5 mmol scale. Solid catalyst
was added to all other reagents at 0 °C, the ice bath was immediately
removed, and the solution was allowed to warm to room temperature unless
otherwise indicated. Reactions were generally complete within 30 min.
b Ratio of regioisomers determined by crude NMR and/or GC, where
applicable. The amount of â isomers refers to the sum of cis and trans
isomers. c Isolated yield for the mixture of R and â isomers unless otherwise
indicated. d Yield refers to isolated pure R product. e This reaction was nearly
identical to entry 6 by crude NMR. The product was not isolated.
A variety of terminal alkynes proved amenable to the reaction,
including those with substantial steric bulk (Table 2). The
reaction is tolerant to a wide range of functional groups,
including halides, alkenes, esters, free alcohols, protected
amines, and even free carboxylic acids. Overall, good yields
and good regioselectivity are maintained through a wide range
of substrates. Limitations of the method include R-quaternary
centers (entry 11), where we presume that steric demands are
too great to allow reactivity, and acyclic 1,6-diynes (entry 12),
presumably due to chelation to the metal center.
(11) Esteruelas, M. A.; Herrero, J.; Oro, L. A. Organometallics 1993, 12, 2377-
2379.
In general, terminal alkynes are significantly more reactive
than internal alkynes (though electronics and neighboring
substitution also play significant roles). This reactivity profile
allows for diyne 32 to react exclusively at the terminal alkyne,
even in the presence of a homopropargylic hydroxyl group at
the internal alkyne to give vinylsilane 33 (eq 1).
(12) Na, Y.; Chang, S. Org. Lett. 2000, 2, 1887-1889.
(13) Murai, T.; Kimura, F.; Tsutsui, K.; Hasegawa, K.; Kato, S. Organometallics
1998, 17, 926-932.
(14) (a) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2001, 123, 12726-12727.
(b) Trost, B. M.; Ball, Z. T.; Joege, T. J. Am. Chem. Soc. 2002, 124, 7922-
7923. (c) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2004, 126, 13942-
13944.
(15) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2003, 125, 30-31.
(16) (a) Trost, B. M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5, 1895-
1898. (b) Trost, B. M.; Ball, Z. T.; Jo¨ge, T. Angew. Chem., Int. Ed. 2003,
42, 3415-3418.
(17) Kawanami, Y.; Sonade, Y.; Mori, T.; Yamamoto, K. Org. Lett. 2002, 4,
2825-2827.
(18) Trost, B. M.; Pinkerton, A. B. Angew. Chem., Int. Ed. 2000, 39, 360-362.
Trost, B. M.; Pinkerton, A. B. J. Am. Chem. Soc. 1999, 121, 1988-1989.
Trost, B. M.; Fraisse, P. L.; Ball, Z. T. Angew. Chem., Int. Ed. 2002, 41,
1059-1061.
(19) Fleming, I.; Newton, T. W.; Roessler, F. J. Chem. Soc., Perkin Trans. 1
1981, 2527-2532.
The use of benzyldimethylsilane (BDMS-H) in alkyne
hydrosilylations was deemed especially useful (entries 9 and
10). The BDMS group of vinylsilane 29 is activated in under
10 min upon treatment with TBAF in DMF at 0 °C through
protodesilylation of the benzyl group, affording an Si-X
(20) Betzer, J. F.; Pancrazi, A. Synlett 1998, 1129.
(21) Betzer, J. F.; Delaloge, F.; Muller, B.; Pancrazi, A.; Prunet, J. J. Org. Chem.
1997, 62, 7768-7780. Stoltz, B. M.; Kano, T.; Corey, E. J. J. Am. Chem.
Soc. 2000, 122, 9044-9045. Kazmaier, U.; Schauss, D.; Pohlman, M. Org.
Lett. 1999, 1, 1017-1019. Kazmaier, U.; Pohlman, M.; Schauss, D. Eur.
J. Org. Chem. 2000, 2761-2766.
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A R T I C L E S
Trost and Ball
Table 2. Hydrosilylation of Terminal Alkynes To Afford Markovnikov Addition Productsa
a All reactions were performed 0.5 M in CH2Cl2 on 0.2-0.5 mmol scale with 1.2 equiv of silane unless otherwise indicated. Reactions were generally
complete within 1 h. b Ratio of branched (b) to linear (l) regioisomers determined by crude NMR and GC, where applicable. c Isolated yield for the mixture
of branched and linear isomers unless otherwise indicated. d Yield refers to isolated pure branched product. e 100% conversion. f The complicated olefinic
1
region of the crude H NMR made a reliable determination of the product ratios difficult, though significant linear material was not isolated. g The solvent
for this reaction was acetone.
Scheme 1. Synthetic Utility of Benzyldimethylsilanes
terminal alkynes with a wide variety of silanes including alkoxy,
trialkyl, aryl, and benzylic, and even halosilanes (see below).
Reaction efficiency and catalyst loading are generally best with
trialkylsilanes. Extremely hindered silanes (i-Pr3SiH) fail to
react, as does diethylsilane. This last failure is interesting and
may be mechanistically important in light of recent proposals
for unique reaction pathways available to dihydridosilanes.26
Hydrosilylation catalyzed by complex 7 succeeds in a wide
variety of solvents. Our initial screen with trialkylsilanes
indicated that chlorinated, ethereal, and even homogeneous
aqueous mixtures are successful. Only DMF resulted in a
particularly poor reaction. Our initial solvent of choice was
species, likely the silanol.22 This reactive silane intermediate
can then be used in situ under mild conditions, such as in
palladium-catalyzed cross-coupling (Scheme 1).16a
dichloromethane. However, we became interested in the hy-
drosilylation of internal alkynes with the rather sluggish
BDMS-H for the purposes of obtaining ketone products after a
subsequent oxidation.16b In CH2Cl2, turnover was insufficient,
even in the presence of rather large excesses of silane (Scheme
2, condition a). A brief re-examination of the reaction led to
the use of acetone as a solvent, which gave significantly better
turnover at lower catalyst loading (condition b). Acetone
provides negligible changes in regioselectivity, and it is
important to note that although acetone provides better turnover
The broad utility of structurally dissimilar silanes is note-
worthy in reactions catalyzed by complexes 6 and 7. Maintaining
selectivity across electronically differentiated silanes is generally
difficult. For example, many of the catalysts developed for trans
addition to terminal alkynessforming the â-vinylsilanessucceed
only for alkyl- and arylsilanes and are poorly selective when
synthetically important alkoxysilanes are employed.23,24 Solu-
tions to this problem have been rare.25 In contrast, we observe
exclusively trans addition products and good R-selectivity for
(24) Tanke, R. S.; Crabtree, R. H. Organometallics 1991, 10, 415-418. Tanke,
R. S.; Crabtree, R. H. J. Am. Chem. Soc. 1990, 112, 7984-7989. Esteruelas,
M. A.; Nurnberg, O.; Olivan, M.; Oro, L. A.; Werner, H. Organometallics
1993, 12, 3264-3272. Ojima, I.; Kumagai, M.; Nagai, Y. J. Organomet.
Chem. 1974, 66, C14-C16.
(25) Faller, J. W.; D’Alliessi, D. G. Organometallics 2002, 21, 1743-1746.
(26) Glaser, P. B.; Tilley, T. D. J. Am. Chem. Soc. 2003, 125, 13640-13641.
(22) Denmark, S.; Wehrli, D.; Choi, J. Org. Lett. 2000, 2, 2491-2494.
(23) Jun, C. H.; Crabtree, R. H. J. Organomet. Chem. 1993, 447, 177-187.
Ojima, I.; Clos, N.; Donovan, R. J.; Ingallina, P. Organometallics 1990, 9,
3127-3133.
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Alkyne Hydrosilylation Catalyzed by [Cp*Ru(MeCN)3]PF6
A R T I C L E S
1-cyclohexenyl-triethylvinylsilane reported elsewhere.28 This
result indicates that the trans addition phenomenon is generals
that it applies to terminal alkynes in addition to internal alkynes.
The importance of the result with the sterically demanding
terminal alkynes is mechanistically significant. Pathways operat-
ing by cis addition/isomerization mechanisms would be expected
to show an erosion in stereochemistry as the steric bulk of the
alkyne substituent is increased. Indeed, in other reports of clean
trans additions to terminal alkynes (to provide (Z)-â-vinylsilane
products), substantial increases in the steric bulk of the alkyne
substituents led to erosion in Z/E selectivity. This observation
was ascribed to the relative similarity of steric bulk between
silyl and R groups.23 However, we observed no cis addition
products by deuterium incorporation for the quite hindered
alkyne 26 (Scheme 3, eq ii), making it unlikely that the
hydrosilylation proceeds through a species such as 42.
Scheme 2. Solvent Optimization
Scheme 3. Deuterium Labeling of Terminal Alkynes
Internal Alkynes
Many of the most important extant alkyne hydrosilylation
catalysts are unreactive toward internal alkynes, and there is a
dearth of useful hydrosilylation catalysts for this substrate
class.1,10 We were pleased to find that the same catalyst and
conditions which provided regioselective hydrosilylation of
terminal alkynes induced clean hydrosilylation of internal
alkynes to provide trisubstituted vinylsilanes (Table 3). The
observed products are exclusively (Z)-vinylsilane isomers, the
product of a trans addition process. This selectivity has been
extremely robust; in extensive examination of a wide range of
internal alkynes, we have not observed the formation of any
(E)-vinylsilanes.29,30 This finding is the only reported direct trans
addition in the intermolecular hydrosilylation of alkynes.31
Functional group tolerance and reaction scope for the reaction
are similar to those of terminal alkynes (Table 3). Internal
alkynes often produce nearly quantitative yields (>95%)shigher
than those of terminal alkynessperhaps reflecting that, for a
terminal alkyne, there exists the possibility for alkynyl C-H
insertion and/or vinylidene-based side reactions and catalyst
decomposition pathways not possible with internal alkynes.32
In pursuing regioselectivity with internal alkynes, an initial
screen of a few alkynes provided somewhat mixed results (Table
3). Both 1,5- and 1,6-enynes provided very good regioselectivity
(entries 1 and 2). At first, the basis for this selectivity seemed
to be coordination of the pendant olefin in some sense, though
how the observed regiochemistry fits with a mechanistic picture
developed later33 is not obvious, and other factors may be at
play. In addition, pendant C-C unsaturation with the op-
portunity for chelation to a ruthenium center also results in
decreased reactivity, turnover, and yield, and so it has not proven
to be a general approach to obtaining regiocontrol in the
hydrosilylation of internal alkynes.
numbers, we do not have reliable data on changes in reaction
rate with solvent. The effect is general for all-carbon-substituted
silanes, and acetone is the solvent of choice for these silanes.
Yields for hydrosilylations with alkoxysilanessincluding in-
tramolecular reactions15sare significantly reduced in acetone
and in protic solvents as a result of extensive decomposition,
and so dichloromethane remains the better choice for these
reactions. This is presumably due to the difficulty in obtaining
truly anhydrous acetone and to the hydrolytic instability of
alkoxysilanes in the presence of a Lewis-acidic ruthenium
complex.
The stereochemistry of addition is not pertinent with terminal
alkynes in cases where R-silane formation is predominant, but
the observation of a trans addition process with internal alkynes
led us to establish the stereochemistry for terminal cases by
means of a deuterium labeling experiment. Pleasantly, reaction
of the alkyne 8 with triethylsilane-d and complex 7 provided a
1
single product, 40 (Scheme 3, eq i). Analysis with H NMR
indicated 100% incorporation of deuterium at a single vinyl
position resulting from trans addition.27 The same experiment
with rather hindered alkyne 26 gave the same result (Scheme
3, eq ii). The assignment of trans addition stereochemistry in
(28) Kang, S. K.; Hong, Y. T.; Lee, J. H.; Kim, W. Y.; Lee, I.; Yu, C. M. Org.
Lett. 2003, 5, 2813-2816. Fuerstner, A.; Kollegger, G.; Weidmann, H. J.
Organomet. Chem. 1991, 414, 295-305.
(29) Small amounts (ca. 5%) of the (E)-vinylsilanes have been reported by
Fu¨rstner in the hydrosilylation of rather small macrocyclic alkynes (12-
14 members) with complex 7. Larger rings resulted in only (Z)-vinylsilane
products. See ref 30.
(30) Fu¨rstner, A.; Radkowski, K. Chem. Commun. 2002, 2182-2183. Lacombe,
F.; Radkowski, K.; Seidel, G.; Fu¨rstner, A. Tetrahedron 2004, 60, 7315-
7324.
1
silane 40 is based on H NMR shifts of related compounds.
The cis (δ 5.28-5.37) and trans (δ 5.65-5.75) protons relative
to silicon of R-triethylsilyl vinylsilanes are quite distinct, both
for other substrates in this study and in closely related
(27) Notably, a single experiment repeating these results with complex 6 appears
to contain 15-20% 1H at the trans addition position. We have not ruled
whether H-D exchange with the terminal alkyne prior to hydrosilylation
is to blame for this anomaly, though it is possible that under some conditions
a cis addition might be a minor, competing pathway.
(31) Denmark, S. E.; Pan, W. Org. Lett. 2003, 5, 1119-1122.
(32) Trost, B. M.; Rhee, Y. H. J. Am. Chem. Soc. 2003, 125, 7482-7483. Trost,
B. M.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124, 2528-2533.
(33) Chung, L. W.; Wu, Y.-D.; Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc.
2003, 125, 11578-11582.
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A R T I C L E S
Trost and Ball
Table 3. Hydrosilylation of Internal Alkynes with Complex 7a
a All reactions were performed 0.5 M in CH2Cl2 on 0.2-0.5 mmol scale; 1.2 equiv of silane and 1 mol % complex 7 were employed unless otherwise
indicated. Reactions were generally complete within 1 h. b Ratio of major:minor regioisomers determined by NMR and/or GC analysis of the crude reaction
mixture. Only trans addition products were observed. c Isolated yield is for the mixture of regioisomers unless otherwise indicated. d Yield refers to isolated
pure major product. e 10 mol % catalyst loading. f 4 mol % catalyst loading. g Product isolated as trans olefin after protodesilylation. See ref 14b.
We also examined simple steric differentiation, which af-
forded quite selective cis addition in a study by Molander.10
Discrimination of a 2-alkyne provided modest regioselectivity
(2.4:1) for the hydrosilylation product with silicon in the less
sterically demanding position (Table 3, entry 3). It may be that
the selectivity in this case is due more to electronic than to steric
considerations. Problems with this approach surfaced when more
sterically demanding alkynes were studied in an attempt to
improve steric differentiation (entry 4), or when aryl substituents
were included (entry 5). In these cases, complete regioselectivity
for the hydrosilylation regioisomer with silicon in the more
sterically demanding position was observed. This result is in
line with that observed with terminal alkynes. However, low
conversion was observed even with quite elevated catalyst
loadings. It became apparent that steric differentiation would
be troublesome if reactivity dropped when sufficient steric bulk
was introduced to induce improved regioselectivity.34
Another possibility is the use of proximal heteroatoms for
direction, which has been observed to afford direction in limited
cases.12,13 Again, the results were initially mixed. The use of a
homopropargylic alcohol afforded a 5:1 mixture of regioisomers,
with both isomeric siloxanes isolated after intramolecular
cyclization onto the pendant alcohol (Table 3, entry 7). However,
a γ,δ-alkynyl ketone substrate did not demonstrate any direction
from the carbonyl group (entry 6). A primary propargylic acetate
also afforded rather useful levels of regioselectivity (6:1, entry
8), as did the methyl acetal of 2-butynal (entry 9). The relative
contributions of the several factors which could contribute to
this selectivity have not been examined. Although initially it is
tempting to invoke steric arguments, the strong directing effects
later observed with propargylic alcohols indicate that electronic
effects are likely important in this case.
Propargylic Alcohols
We became interested in the hydrosilylation of propargylic
alcohols. These compounds are readily synthesized in enantio-
merically enriched form,35 and several interesting methodologies
based on vinylsilanes bearing allylic alcohols have been
developed, despite the circuitous means previously available for
accessing such compounds.36 Unfortunately, all attempts to
perform hydrosilylation of propargylic alcohols with triethoxy-
silane resulted only in extensive decomposition (Scheme 4), and
no vinylsilane was ever isolated. This was a surprise, as a
terminal alkyne propargylic alcohol could be used as an efficient
substrate (see Table 2, entry 4).
Reasoning that poor product stability may be to blame for
the observed decomposition, we switched to triethylsilane. This
provided an immediate benefit, as the â-silyl allylic alcohol was
formed in quantitative yield and 13:1 regioselectivity (Table 4,
entry 2). Again, only the (Z)-products of a trans addition process
(35) Ojima, I., Ed. Catalytic Asymmetric Synthesis, 2nd ed.; Wiley-VCH: New
York, 2000. Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem. Soc.
2000, 122, 1806-1807. Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc.
2001, 123, 9687-9688. Boyall, D.; Frantz, D. E.; Carreira, E. M. Org.
Lett. 2002, 4, 2605-2606.
(36) (a) Hasan, I.; Kishi, Y. Tetrahedron Lett. 1980, 21, 4229-4232. (b) Taguchi,
H.; Ghoroku, K.; Tadaki, M.; Tsubouchi, A.; Takeda, T. Org. Lett. 2001,
3, 3811-3814.
(34) Reactivity in a trans addition process can be achieved for such hindered
substrates with intramolecular hydrosilylation reactions. See ref 15.
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Alkyne Hydrosilylation Catalyzed by [Cp*Ru(MeCN)3]PF6
A R T I C L E S
Table 4. Selective Hydrosilylation of Propargylic Alcohols Catalyzed by Ruthenium Complex 3.1a
a All reactions were performed with 1.2 equiv of silane in acetone from 0 °C to room temperature and were complete within 30 min unless otherwise
indicated. b Isolated yield of both isomers except where indicated. Numbers in parentheses refer to yields based on unreacted starting material. c Regiochemistry
of silane addition determined by crude 1H NMR or GC. Both isomers are (Z)-stereochemistry. d Reaction performed with 1.5 equiv of silane in CH2Cl2.
e Reaction performed in CH2Cl2. f Isolated yield of pure major isomer.
75,37a the method described here allows for rapid, atom-
Scheme 4. Failed Attempts at Propargylic Alcohol Hydrosilylation
economical, and catalytic access to dienoate 76 in a stereo-
specific manner. This route compares favorably to other routes
to similar compounds, where obtaining olefin isomer selectivity
is often a challenge.37b
were observed. Although appropriate for some applications,36a
triethylvinylsilanes are not extensively useful intermediates, and
we were interested in a silane with more robust and facile
chemistries in further elaboration reactions. The use of
monoalkoxy dimethylsilanes did allow isolation of some of the
desired silacycle, but the product was so unstable that only very
poor yields could be obtained after careful purification on florisil
(entry 1). A more bulky secondary alcohol greatly improved
product stability, and the desired vinylsilane was isolated in
respectable yield (entry 3).
Although for some subsequent applications the transient
formation of the unstable monoalkoxy dimethylsilyl product
The synthesis of stereodefined polyenoates is often called for
in the synthesis of natural product targets. When combined with
palladium-catalyzed alkyne-alkyne coupling to produce enyne
(37) (a) Trost, B. M.; Sorum, M. T.; Chan, C.; Harms, A. E.; Ruhter, G. J. Am.
Chem. Soc. 1997, 119, 698-708. (b) Smith, A. B.; Walsh, S. P.; Frohn,
M.; Duffey, M. O. Org. Lett. 2005, 7, 139-142.
9
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A R T I C L E S
Trost and Ball
Table 5. Hydrosilylation of Alkynyl Carbonyl Compounds
a Reactions were performed using 1.2 equiv of silane at 0.5 M in acetone for 30 min. b Ratio of â-vinylsilane:R-vinylsilane determined by analysis of
1
crude H NMR. In all cases only (Z)-vinylsilane isomers were observed. c Yield in parentheses is based on recovered alkyne.
Scheme 5. Chemoselectivity among Alkynes
would suffice, and for some others trialkylvinylsilanes are
suitable, we sought a silane that would combine the benefits of
both of these silanes. We sought to maintain clean reactivity
and good product stability while permitting a wide variety of
subsequent operations. After examining several choices, includ-
ing chlorodimethylsilane and allyldimethylsilane, and consider-
ing more exotic choices, in our hands the optimal choice was
BDMS-H, which reacts in a manner similar to triethylsilane,
requiring only slightly higher catalyst loadings (generally
2-4%). BDMS-H performs well and tolerates a range of
some functional groups, and direct hydrosilylation is a more
functional groups (Table 4). Propargylic alcohol substrates are
atom-economical process.20,38 A variety of substituted silanes
can be employed. Although γ-alkoxy groups result in generally
lower yields or turnover numbers (entries 6 and 9), the
unprotected γ-hydroxy compounds are well-tolerated (entries
themselves unique; the presence of neighboring olefins typically
produces poor reactivity, but a propargylic hydroxyl allows for
significant reactivity (entry 8). In addition, propargylic alcohol
substrates succeed even in the presence of substantial steric bulk.
7, 8). An alkynyl acid is also a good substrate for hydrosilylation
Entry 9 illustrates reactivity with a highly hindered alkyne which
(entry 10). Interestingly, only 1.2 equiv of silane need be
proceeds with 3% catalyst loading (cf. Table 3, entry 4, which
employed with the carboxylic acid functionalitysa fact dem-
reacts to only 40% conversion with 10% catalyst loading).
onstrating the chemoselectivity of the ruthenium-catalyzed
Indeed, entry 9 undergoes hydrosilylation, whereas 1,3-enynes
reaction. Alkoxysilanes are also competent reaction partners
without propargylic free hydroxyls so far examined fail to react.
(entry 5), but the regioselectivity is somewhat compromised,
r,â-Alkynyl Carbonyl Compounds
in line with the trend generally observed for other substrate
classes.
The final and probably most robust class of alkynes which
we have found amenable to intermolecular hydrosilylation
is R,â-alkynyl carbonyl compounds. The use of catalytic
[Cp*Ru(MeCN)3]PF6 (7) in the hydrosilylation of alkynyl esters
and ketones provides exclusive trans addition to the (Z)-olefin
isomer, with very good selectivity for the â-silyl regioisomer
(Table 5). Similar regiochemistry is accessible by stoichiometric
silyl cupration of the alkyne, but the silyl group is generally
limited to SiMe2Ph, the basic silylcuprate prevents tolerance of
The effects of steric demand and electronic perturbations on
reactivity result in significant differences in hydrosilylation
kinetics among internal alkynes (Scheme 5). As shown, a
competition experiment between internal alkynes determined
that selective hydrosilylation at an electron-deficient alkynone
in the presence of a dialkyl alkyne is possible. Reaction of the
(38) Fleming, I.; Newton, T. W.; Sabin, V.; Zammattio, F. Tetrahedron 1992,
48, 7793-7802.
9
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Alkyne Hydrosilylation Catalyzed by [Cp*Ru(MeCN)3]PF6
A R T I C L E S
ynone substrate is preferred in a 9:1 ratio, as determined by 1H
NMR analysis of the crude reaction mixture.
Scheme 6. Synthesis of Tethered Diels-Alder Substrates with
Hydrosilylation
Orthogonal Tethers for the Diels-Alder Reaction from
H-Si-X Silanes
The Diels-Alder reaction constitutes one of the most
powerful and widely utilized reactions available to the organic
chemist. Highly activated dienes and dienophiles often provide
good intermolecular reactivity and regiocontrol. However,
relatively unactivated dienes and dienophiles are often quite
unreactive and/or suffer from poor regiocontrol. For this reason,
intramolecular Diels-Alder reactions (IMDAs) have been
extensively studied as a means of achieving both pre-organiza-
tion for regio- and stereocontrol and increased reactivity.
Removable tethers allow the advantages of IMDAs in cases
where bicyclic products are not desired, and silicon tethers are
especially useful in this context because they can serve as
“traceless” tethers after protodesilylation or as alcohol surrogates
through oxidation.
While disiloxane tethers are one approach, the direct use of
vinyl- or dienylsilanes allows increased synthetic efficiency,
stability, and potentially selectivity. Very simple vinylsilane
tethers are readily synthesized by trapping vinyl organometallic
reagents (usually RMgX or RLi) with dichlorosilanes.40 This
approach places limits on the functional groups present in the
vinylmetallic, and the use of difunctional dichlorosilanes may
require large excess of the silyl reagent for smooth monoadditon
unless special reagents are employed.40a
We were thus excited to find that alkyne 8 reacts with
HMe2SiCl in the presence of very low levels of complex 7 to
provide presumably an intermediate chlorosilane (Scheme 6,
path b). This intermediate was not isolated or observed, but
rather it was treated directly with triethylamine and sorbol to
give an improved yield of the desired triene in a one-pot process
that eliminated the need to isolate and purify a silyl hydride
intermediate such as 99. Stork has previously shown that similar
1,1-disubstituted vinylsilanes undergo cycloaddition under
thermal conditions.40a In a Teflon-sealed screw-cap vial, triene
100 was smoothly converted to bicyclic system 102 at 180 °C
in benzene. (Stork, using a sealed tube, saw reaction of very
similar systems at 160 °C. We suspect that the elevated
temperatures required for our cycloadditions are due to a lower
internal temperature in our apparatus. The same trend is
observed for compound 103 below.)
We also turned our attention to a more substituted system.
Taking advantage of the good regiocontrol available to R,â-
alkynoates, the one-pot chlorodimethylsilane protocol allowed
clean formation of the tethered triene 103. Thermal cycloaddition
again provided clean, though sluggish, conversion to what
appeared to be the cycloaddition product. Upon exposure to
silica, the product decomposed to a mixture of at least two new
products. Therefore, we directly treated the crude Diels-Alder
adduct 104 with either protodesilylation or oxidation conditions
to provide the cyclohexene products 105 and 106, respectively
(Scheme 7). As discussed earlier, both protodesilylation and
silane oxidation are extremely sluggish processes with tertiary
silanes. However, a hydroxyl substituent â to the silane activates
the silane through formation of a five-membered-ring silicate.40a,43
Oxidation and protodesilylation processes thus proceed at 60
and 80 °C, respectively, to give good yields of the desired
cyclohexene products.
Straightforward access to some disubstituted vinylsilanes has
been demonstrated. However, more complex substrates such as
trisubstituted vinylsilanes are generally only poorly accessible
by circuitous means and hence are little investigatedseven
though they potentially allow access to synthetically challenging
products and quaternary stereocenters.41 Given the ready access
to vinylsilane species provided by ruthenium-catalyzed hydro-
silylation, we sought to pursue structures that would be difficult
to obtain by other means. We synthesized42 the dienyl silane
99 (HMe2Si)2NH, ∆; Scheme 6) and found that coupling with
a terminal alkyne catalyzed by complex 7 did indeed produce
the desired triene (Scheme 6). However, the yield was modest,
and high loading of ruthenium was required for conversion. The
efficiency of obtaining the IMDA substrate (in terms of yield
and catalyst loading) could be improved by delaying the diene
introduction until after the vinylsilane was formed. A silyl
hydride containing a chloride leaving groupssuch as HMe2SiCls
could be used as an orthogonal means of introducing the two
tethering units (path b). This should prevent the need for large
excesses of the silane as in many traditional tethering protocols
where dichlorosilanes are used. The process demonstrates the
success of halogenated silanes in hydrosilylation reactions
catalyzed by complex 7 and should be applicable to building
“traceless” tethers for any number of intramolecular reactions.
(39) Bols, M.; Skrydstrup, T. Chem. ReV. 1995, 95, 1253. Fensterbank, L.;
Malacria, M.; Sieburth, S. Synthesis 1997, 813. Gauthier, D. R., Jr.; Zandi,
K. S.; Shea, K. J. Tetrahedron 1998, 54, 229.
(40) (a) Stork, G.; Chan, T. Y.; Breault, G. A. J. Am. Chem. Soc. 1992, 114,
7578-7579. (b) Brosius, A. D.; Overman, L. E.; Schwink, L. J. Am. Chem.
Soc. 1999, 121, 700-709. (c) Shea, K. J.; Zandi, K. S.; Staab, A. J.; Carr,
R. Tetrahedron Lett. 1990, 31, 5885-5888. (d) Gauthier, D. R., Jr.; Zandi,
K. S.; Shea, K. J. Tetrahedron 1998, 54, 2289-2338.
The cycloaddition product relative stereochemistry was
determined by NOE analysis. The identity of 102 was estab-
lished from a 1,3-diaxial NOE as shown below. The bold “H”
(41) Tamao, K.; Kobayashi, K.; Ito, Y. J. Am. Chem. Soc. 1989, 111, 6478-
6480.
(42) Marshall, J. A.; Yanik, M. M. Org. Lett. 2000, 2, 2173-2175.
(43) Stork, G.; Chan, T. Y. J. Am. Chem. Soc. 1995, 117, 6595-6596.
9
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A R T I C L E S
Trost and Ball
Scheme 7. Alkyne Hydrosilylation To Build More Complex
Substrates for Silicon-Tethered Diels-Alder Reactions
and B3LYP/6-31G(d) levels (Figure 1).45,46 All three gave
essentially the same result: the exo transition state is favored
by 3-4 kcal/mol. Specifically, the ∆∆Gq values for the zero-
point-corrected transition-state energies were 3.2 [AM1], 4.0
[HF/3-21G(*)], and 3.7 kcal/mol [B3LYP/6-31G(d)]. Initial
results indicate that the endo product is 4-5 kcal/mol more
stable than the exo; thus, the exo product is kinetically preferred,
but the thermodynamic product is endosthe opposite of the
usual (intermolecular) textbook cases. The transition states
themselves are rather different. The disfavored endo transition
state (left) is nearly perfectly synchronous, with incipient bond
lengths of 2.19 and 2.21 Å. The preferred exo transition state
is highly asynchronous, however, with incipient bond distances
of 2.00 and 2.54 Å. Although this might suggest that the latter
transition state more nearly resembles a Michael addition, there
was little evidence of extra charge separation in the calculation.
indicates protons with a very small (<1 Hz) coupling, consistent
with the perpendicular arrangement of these protons in the cis
structure. The alternative trans-102 should have a rather large
coupling constant, given the nearly coplanar arrangement of the
bolded atoms in that structure.
The structure of protodesilylation product 105 could be
established through a similar 1,3-diaxial NOE. In this case, the
large (10 Hz) coupling constant exhibited by antiperiplanar
hydrogen atoms is indicative of the product from an exo-mode
Diels-Alder cyclization with respect to the ester substituent.
Figure 1. Calculated transition-state structures.
Conclusion
The Cp*Ru+-catalyzed hydrosilylation of a wide variety of
terminal and internal as well as conjugated and nonconjugated
alkynes proceeds rapidly and with good regioselectivity in most
cases. In addition, a diverse array of silanes ranging from trialkyl
to trialkoxy react. Based upon a qualitative observation of
required catalyst loading for complete reaction, a rough order
of reactivity can be suggested as SiEt3 ≈ SiMe2Cl > SiMe2OR
Stereochemical proof of the oxidation product 106 required
NOESY analysis, which identifies the exo adduct through a 1,3-
diaxial correlation together with the aforementioned 10.5 Hz
antiperiplanar coupling.44
Given the exo product formation in opposition to that typically
expected of intermolecular Diels-Alder reactions, we became
interested in determining the basis of the observed selectivity.
The endo and exo transition states were located for this reaction
and verified by frequency calculations at the AM1, HF/3-21G(*),
(45) All calculations were performed by using GAUSSIAN 98. The built-in
default thresholds for wave function and gradient convergence were
employed, transition states were located by using the QST3 option, and
they were verified by analytical frequency calculations.
(44) The exo adduct is more in line with NMR data at hand than the endo product
previously proposed for a similar (less substituted) case. See ref 40a.
(46) Frisch, M. J.; et al. Gaussian98; Gaussian, Inc.: Pittsburgh, PA, 1998.
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Alkyne Hydrosilylation Catalyzed by [Cp*Ru(MeCN)3]PF6
A R T I C L E S
Scheme 8. Hydrosilylation-Metathesis for Cyclic Vinylsilane
Formation
Figure 2. Proposed mechanism for transition addition without cis-trans
isomerization.
≈ Si(OR)3 > SiMe2Bn ≈ SiMe2Ph. The apparent lower
reactivity of the last two, especially SiMe2Bn (BDMS), is
somewhat surprising, given the high reactivity of triethylsilane.
The high affinity of this type of ruthenium complex to coordinate
with an aromatic ring may account for this apparent anomaly.
Nevertheless, the reactions of BDMS-H still proceed in good
yields with reasonable rates and catalyst loadings. The products
of hydrosilylation with this silane are particularly useful for
subsequent transformations based upon the fact that the benzyl
group is chemoselectively replaced by a hydroxy group with
TBAF, enabling cross-coupling and Tamao-Fleming oxidations.
The observation of a clean trans addition in each case speaks
against a mechanism involving an initial cis addition followed
by isomerization before the final reductive elimination. This
stereochemical course for the Markovnikov hydrosilylation of
the two terminal alkynes further attests to this conclusion. A
mechanism involving a direct three-component addition, as
depicted in Figure 2, emerged from calculations.33 While it
provides a nice rationalization for a direct trans addition, it also
provides some enlightenment regarding the regiochemistry. The
hypervalency involved in the transition state for H delivery
should favor its delivery to the sterically more accessible alkyne
carbon, which accounts for the Markovnikov addition with
terminal alkynes and several internal alkynes. According to this
model, the role of a propargylic alcohol substituent to direct
the reaction wherein this substituent resides on R1 is inductive;
an electronegative substituent adjacent to the carbenoid center
of the ruthenacyclopropene (i.e., if it were in R2) is disfavored.
This type of effect also explains the regioselectivity with respect
to R,â-unsaturated carbonyl substrates. The example of Table
4, entry 9, is quite interesting in this regard. In the competition
between a vinylogous carbonyl substituent and a propargylic
alcohol, the latter wins although the steric factor may also be a
contributor.
The mechanistic hypothesis may illustrate the unique nature
in metal catalysts, such as ruthenium, occupying an intermediate
place on the periodic table between late transition metals
(palladium, rhodium), which exhibit facile oxidation-reduction,
and early transition metals and actinides (titanium, thorium),
which act through polar mechanisms due to the inaccessibility
of oxidation-reduction cycles. In the mechanism proposed here,
oxidative addition into the Si-H bond is not energetically
feasible. Instead, the silane is activated through a σ-complex in
a step reminiscent of early transition metals. The formal
oxidation of the ruthenium center certainly can occur, however,
to provide the vinylruthenium intermediate. At this point
additional stabilization of the ruthenium(IV) center is provided
by the C-C π-bond as η2-coordination of the vinyl ligand.
The use of the hydrosilylation as an entry to the silicon-
tethered Diels-Alder reaction significantly enhances the utility
of this strategy. The exo selectivity provides an additional benefit
beyond the regioselectivity compared to the untethered case.
Combined with the ability to perform both oxidative desilylation
and protodesilylation allows for the synthetic equivalent of a
â-hydroxy-R,â-unsaturated ester dieneophile.
More mechanistic work is clearly called for. Nevertheless, a
reasonable case exists that a new mechanistic principle may be
involved. From a practical synthetic point of view, the unusual
regio- and geometric selectivity adds a new dimension to the
atom-economic hydrosilylation of alkynes complementary to
other catalytic systems and the utility of the resultant vinylsilanes
for further structural elaborations.
The complex 7 affords the first general access to 1,1-
disubstituted vinylsilanes, as well as the first hydrosilylation of
internal alkynes by a trans addition pathway. Importantly, a
diverse set of silane substituents are compatible with the hydro-
silylation reaction, including alkyl, alkoxy, aryl, 2-furanylmethyl,
and chloro groups. The regioselectivity combined with the
versatility of being able to use almost any type of substituent
in silicon bodes well for synthetic applications. For example,
the requirement for alkoxyvinylsilanes as partners in ruthenium-
catalyzed metathesis47 allows the ring-forming sequence shown
in Scheme 8. The resulting cyclic vinylsilanes can then be
employed for further elaboration such as Tamao-Fleming
oxidation and cross-coupling. We hope that the work presented
here spurs the continued development of silicon as a versatile,
stable, and environmentally benign vinylmetal species for
complex target synthesis. We are intrigued by the prospects that
discoveries made in the course of hydrosilylation may portend
transition-metal-catalyzed trans addition processes with alkynes
as a general synthesis of other olefin classes.
Experimental Section
General Procedure for the Hydrosilylation of Simple Alkynes:
5-Acetyloxy-2-(triethylsilyl)-1-pentene, 9. The alkyne 8 (50 µL, 0.38
mmol), in a flask under Ar, was dissolved in CH2Cl2 (0.75 mL, 0.5 M
solution) and treated with triethylsilane (72 µL, 0.45 mmol). The flask
was cooled to 0 °C, and solid 6 (1.6 mg, 0.0038 mmol) was added at
this temperature. The flask was immediately allowed to warm to
(47) Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. J. Am. Chem.
Soc. 2000, 122, 3783-3784. Pietraszuk, C.; Marciniec, B.; Fischer, H.
Organometallics 2000, 19, 913. Denmark, S. E.; Yang, S. M. Org. Lett.
2001, 3, 1749.
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A R T I C L E S
Trost and Ball
ambient temperature and stirred for 30 min. The crude reaction mixture
was concentrated under reduced pressure and immediately applied to
a silica gel column (eluent with 20:1 petroleum ether:ether). After
purification, 78 mg (86%) of the desired 1,1-disubstituted silane was
isolated as a clear, colorless oil.
(benzyldimethylsilanyl)-7-(4-methoxy-benzyloxy)-1-phenyl-undec-4-en-
6-ol (53.6 mg, 78%) after purification on a silica gel column (eluent:
6:1, then 4:1 petroleum ether:ether).
1
Rf: 0.16 (4:1 petroleum ether:ether). H NMR (300 MHz, CDCl3):
δ 6.85-7.23 (m, 14H), 6.00 (d, J ) 9.5 Hz, 1H), 4.45-4.62 (m, 2H),
4.11-4.17 (m, 1H), 3.87 (s, 3H), 3.12-3.25 (m, 1H), 2.57 (t, J ) 8.1
Hz, 2H), 2.39 (d, J ) 3.2 Hz, 1H), 2.01-2.27 (m, 4H), 1.26-1.67 (m,
8H), 0.89 (t, J ) 6.8 Hz, 3H), 0.08-0.12 (m, 6H). 13C NMR (125
MHz, CDCl3): δ 159.7, 144.5, 142.6, 141.9, 140.0, 130.6, 129.9, 128.7,
128.61, 128.57, 128.42, 126.0, 124.5, 114.2, 83.2, 73.1, 72.7, 55.6,
38.2, 36.1, 32.3, 31.3, 28.2, 26.9, 23.2, 14.3, -1.1, -1.4. IR (thin
film): 3585 (br), 2931, 2361, 1612, 1514, 1249 (s), 1035, 828, 699
cm-1. Anal. Calcd for C34H46O3Si: C, 76.93; H, 8.73. Found: C, 77.04;
H, 8.83.
General Procedure for Ruthenium-Catalyzed Hydrosilylation of
r,â-Alkynyl Carbonyl Compounds: (Z)-5-(Benzyldimethylsilyl)-4-
hepten-3-one, 78. Neat 4-hepyn-3-one (4.14 g, 37.6 mmol) and
benzyldimethylsilane (7.79 mL, 45.1 mmol) were taken up in acetone
(60 mL) at 0 °C under Ar. Solid [Cp*Ru(MeCN)3]PF6 (95 mg, 0.188
mmol) was added, and the ice bath was removed to allow the solution
to reach room temperature. After 30 min, the acetone was removed
under reduced pressure, and the resulting residue was applied directly
to a silica gel plug (ca. 6 cm, eluent 40:1 petroleum ether:ether) to
provide the desired (Z)-vinylsilane (9.61 g, 98%) as a clear, colorless
oil.
Rf: 0.60 (10:1 petroleum ether:EtOAc). 1H NMR (300 MHz,
CDCl3): δ 5.65 (m, 1H), 5.33 (d, J ) 2.7 Hz, 1H), 4.07 (t, J ) 6.8
Hz, 2H), 2.14 (t, J ) 7.8 Hz, 2H), 2.05 (s, 3H), 1.75 (m, 2H), 0.93 (t,
J ) 7.8 Hz, 9H), 0.61 (q, J ) 7.8 Hz, 6H). 13C NMR (75 MHz,
CDCl3): δ 171.2, 147.7, 125.6, 64.2, 32.1, 27.6, 21.0, 7.3, 2.8. IR (thin
film): 2955, 2876, 1745 (s), 1239 (s), 720 cm-1. HRMS-EI (m/z): [M]+
calcd for C13H26O2Si, 242.1702; found, 213.1302 [M - Et].
10-(4-Acetylphenyl)-10-undecenoic Acid Methyl Ester, 35.
Vinylsilane 29 (69 mg, 0.20 mmol) and 4-iodoacetophenone (34 µL,
0.30 mmol) were taken up in THF under Ar at 0 °C. TBAF (0.40 mL,
0.40 mmol, 1.0 M in THF) was then added dropwise, and after 10
min, solid Pd2dba3 (4.5 mg, 0.0050 mmol) was added and the flask
allowed to warm to room temperature. After being stirred for 2 h, the
mixture was diluted with ether (10 mL) and filtered through a plug of
silica gel (ca. 2 cm), washing with additional ether (20 mL). The filtrate
was concentrated under reduced pressure, and the resulting residue was
applied to a silica gel column (eluent 100:8 petroleum ether:EtOAc)
to give 56 mg (89%) of the desired coupling product as a white
crystalline solid.
1
Rf: 0.46 (4:1 petroleum ether:EtOAc). Mp: 38-39 °C. H NMR
(300 MHz, CDCl3): δ 7.93 (d, J ) 8.5 Hz, 2H), 7.48 (d, J ) 8.5 Hz,
2H), 5.35 (d, J ) 1.0 Hz, 1H), 5.16 (d, J ) 1.0 Hz, 1H), 3.66 (s, 3H),
2.60 (s, 3H), 2.51 (t, J ) 7.3 Hz, 2H), 2.29 (d, J ) 7.5 Hz, 2H), 1.60
(m, 2H), 1.43 (m, 2H), 1.22-1.34 (m, 8H). 13C NMR (75 MHz,
CDCl3): δ 197.7, 174.3, 147.8, 146.2, 135.9, 128.4, 126.2, 114.1, 51.4,
35.1, 34.0, 29.1 (2C), 29.0 (2C), 28.1, 26.6, 24.9. IR (thin film): 2930,
2856, 1739 (s), 1683 (s), 1604, 1268, 847 cm-1. Anal. Calcd for
C20H28O3: C, 75.91; H, 8.92. Found: C, 76.12; H, 9.06.
1H NMR (300 MHz, CDCl3): δ 6.98-7.22 (m, 5H), 6.68 (t, J )
1.4 Hz, 1H), 2.55 (q, J ) 7.2 Hz, 2H), 2.37 (s, 2H), 2.15 (qd, J ) 7.3,
1.5 Hz, 2H), 1.13 (t, J ) 7.3 Hz, 1H), 0.89 (t, J ) 7.3 Hz, 1H), 0.10
(s, 6H). 13C NMR (75 MHz, CDCl3): δ 165.4, 140.6, 136.4, 128.4,
128.1, 127.9, 123.8, 36.5, 31.6, 24.8, 13.6, 8.1, -2.3. IR (thin film):
2969, 1690 (s), 1576, 1493, 1246, 1143, 828, 699 cm-1. Additional
characterization is to be provided elsewhere after additional synthetic
operations.
(2R,3S)-1,2,3-Trihydroxy-5-undecanone 1,2-Isopropylidene Ketal,
38. The alkyne 36 (120 mg, 0.50 mmol) and BDMS-H (104 µL, 0.60
mmol) in acetone (1.0 mL) were treated at 0 °C with complex 7 (7.8
mg, 0.015 mmol). The mixture was allowed to warm to room
temperature over 30 min. It was then re-cooled to 0 °C, diluted with
THF (1.5 mL), and TBAF (0.60 mL, 0.60 mmol, 1.0 M solution in
THF) was added dropwise. After 20 min, MeOH (1.0 mL) was
introduced, followed by solid potassium bicarbonate (150 mg, 1.5
mmol) and aqueous H2O2 (0.80 mL, 30% solution). The mixture was
then stirred for 36 h at room temperature, at which time it was diluted
with water (10 mL) and extracted with EtOAc (3 × 10 mL). The organic
extracts were washed with brine (10 mL), dried over Na2SO4, and
concentrated in vacuo. The residue was purified on a silica gel column
(eluent: 85:15:1 petroleum ether:EtOAc:MeOH) to give 99 mg (77%)
of the desired ketone as a single isomeric compound.
1H NMR (500 MHz, CDCl3): δ 4.08 (m, 1H), 3.92-3.95 (m, 3H),
3.27 (br OH, 1H), 2.82 (dd, J ) 7.5, 1.8 Hz, 1H), 2.57 (m, 1H), 2.45
(t, J ) 7.5 Hz, 2H), 1.57 (m, 2H), 1.39 (s, 3H), 1.34 (s, 3H), 1.26-
1.30 (m, 6H), 0.87 (t, J ) 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3):
δ 212.4, 109.4, 77.5, 69.1, 66.9, 45.1, 43.7, 31.5, 28.8, 26.7, 25.1, 23.5,
23.5, 22.4, 14.0. IR (thin film): 3472 (br, OH), 2932 (s), 1713, 1372,
1215, 1066 (s), 851 (w) cm-1. [R]26D: -21.3° (c 1.3, CHCl3). Anal.
Calcd for C14H26O4: C, 65.09; H, 10.14; Found: C, 64.84; H, 9.92.
(()-(S,S)-4-(Benzyldimethylsilyl)-7-(4-methoxy-benzyloxy)-1-
phenylundec-4-en-6-ol, 70. To a solution of (()-(S,S)-7-(4-methoxy-
benzyloxy)-1-phenylundec-4-yn-6-ol (50 mg, 0.13 mmol) and benzyl-
dimethylsilane (23.7 mg, 0.16 mmol) in CH2Cl2 (0.26 mL) was added
[Cp*Ru(MeCN)3]PF6 (7) (3.3 mg, 0.0065 mmol) at 0 °C. The solution
was allowed to warm to room temperature and stirred for 20 min, at
which time TLC analysis indicated incomplete consumption of the
alkyne. Another portion of complex 7 (3.3 mg, 0.0065 mmol) was
added. The solution was stirred for 20 min, filtered through a plug of
florisil, and concentrated under reduced pressure to yield (()-(S,S)-4-
(2Z,2′E,4′E)-3-(Hexa-2,4-dienyloxydimethysilyl)-2-pentenoic Acid
Ethyl Ester, 103. Ethyl 2-pentynoate (200 µL, 1.52 mmol) under Ar
at 0 °C was taken up in CH2Cl2 (3 mL). Dimethylchlorosilane (202
µL, 1.82 mmol, freshly distilled from CaH2) was added, followed by
solid complex 7 (7.0 mg, 0.015 mmol). The flask was allowed to warm
to room temperature and was stirred for 30 min. The flask was then
re-cooled to 0 °C and was treated sequentially with triethylamine (423
µL, 3.03 mmol) and (E,E)-hexadien-1-ol (sorbol) (290 µL, 2.58 mmol).
Additional CH2Cl2 (3 mL) was added to ensure solubility, and the flask
was warmed to room temperature and stirred for 30 min. The mixture
was diluted with benzene (15 mL) and filtered through Celite, washing
with additional benzene (15 mL). The filtrate was concentrated under
reduced pressure and purified by silica gel chromatography (eluent:
20:1 petroleum ether:ether) to afford 371 mg (87%) of the desired silyl
ether as a clear, colorless oil.
1
Rf: 0.26 (4:1 petroleum ether:ether). H NMR (300 MHz, CDCl3):
δ 7.25 (dd, J ) 8.0, 8.0 Hz, 1H), 6.99 (d, J ) 7.2 Hz, 1H), 6.93 (s,
1H), 6.82 (dd, J ) 8.0, 2.4 Hz, 1H), 5.30 (s, 1H), 5.08 (s, 1H), 4.08 (t,
J ) 7.0 Hz, 2H), 3.82 (s, 3H), 2.56 (t, J ) 7.0 Hz, 2H), 2.05 (s, 3H),
1.79 (tt, J ) 7.0, 7.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 171.1,
159.5, 147.1, 142.3, 129.2, 118.6, 113.0, 112.5, 112.1, 63.9, 55.2, 31.7,
27.1, 21.0. IR (thin film): 2956, 1739 (s), 1577, 1240 (s), 1041 cm-1
.
Further characterization will be reported after formation of 114.
(1R,2S,5R,6R)-6-Ethyl-5-hydroxymethyl-2-methylcyclohex-3-
enecarboxylic Acid Ethyl Ester, 105. The starting triene (102 mg,
0.361 mmol) was taken up in benzene-d6 (4 mL) in a Teflon-ringed
screw-top vial and placed in a 180 °C bath for 20 h. The solution was
then transferred to a round-bottomed flask and the solvent removed
under reduced pressure. The residue was taken up in DMF (1.5 mL)
and treated with TBAF (1.5 mL, 1.50 mmol, 1.0 M in THF). The
solution was brought to 75 °C and stirred for 4 h. The mixture was
cooled to room temperature, saturated aqueous NaHCO3 (15 mL) and
water (15 mL) were added, and the mixture was extracted with EtOAc
9
17654 J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005

Alkyne Hydrosilylation Catalyzed by [Cp*Ru(MeCN)3]PF6
A R T I C L E S
(2 × 15 mL). The combined extracts were washed with brine (10 mL),
dried over Na2SO4, and concentrated under reduced pressure. Chro-
matography on silica gel (eluent 10:1 petroleum ether:ethyl acetate)
provided the desired alcohol (56.5 mg, 69%) as a pale yellow oil.
Rf: 0.65 (1:1 petroleum ether:EtOAc). 1H NMR (500 MHz,
CDCl3): δ 5.75 (s, 2H), 4.19 (qd, J ) 7.1, 1.0 Hz, 2H), 3.72-3.82
(m, 2H), 2.52 (m, 1H), 2.44 (m, 1H), 2.31 (dd, J ) 11.4, 10.0 Hz,
1H), 1.91 (m, 1H), 1.33-1.45 (m, 2H), 1.30 (t, J ) 7.1 Hz, 3H), 0.99
(d, J ) 7.0 Hz, 3H), 0.94 (t, J ) 7.4 Hz, 3H). 13C NMR (125 MHz,
CDCl3): δ 176.4, 134.9, 126.4, 62.0, 60.1, 51.4, 40.2, 37.1, 34.9, 22.8,
20.1, 14.4, 11.5. IR (thin film): 3444 (br, OH), 2962, 2877, 1731, 1458,
1375, 1177, 1035 cm-1. HRMS-EI (m/z): [M]+ calcd for C13H22O3,
226.1569; found, 226.1566. Anal. Calcd for C13H22O3: C, 68.99; H,
9.80. Found: C, 69.13; H, 9.59.
leading to compound 104 and Thomas Jo¨ge for important initial
experiments. We acknowledge the National Science Foundation
and the National Institutes of Health (GM13598) for their
generous support of our programs. Z.T.B. received support from
an Althouse Family Stanford Graduate Fellowship. Mass spectra
were provided by the Mass Spectrometry Facility, University
of San Francisco, supported by the NIH Division of Research
Resources.
Supporting Information Available: Full citation of ref 46;
additional experimental procedures and characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. The authors thank Prof. Robert Pascal for
performing calculations on the Diels-Alder transition state
JA0528580
9
J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005 17655