Stereoselective syntheses of trisubstituted olefins via platinum catalysis: α-Silylenones with geometrical complementarity

Article abstract of DOI:10.1021/ja1058197

The stereoselective syntheses of α-silylenones using catalytic PtCl₂ are reported. Via alkyne activation, α- hydroxypropargylsilanes are converted to (Z)-silylenones through a highly selective silicon migration. The complementary (E)-silylenone

Full text of DOI:10.1021/ja1058197

Published on Web 08/06/2010
Stereoselective Syntheses of Trisubstituted Olefins via Platinum Catalysis:
r-Silylenones with Geometrical Complementarity
Douglas A. Rooke and Eric M. Ferreira*
Department of Chemistry, Colorado State UniVersity, Fort Collins, Colorado 80523
Received July 1, 2010; E-mail: emferr@mail.colostate.edu
Table 1. Reaction Optimization
Abstract: The stereoselective syntheses of R-silylenones using
catalytic PtCl2 are reported. Via alkyne activation, R-hydroxypro-
pargylsilanes are converted to (Z)-silylenones through a highly
selective silicon migration. The complementary (E)-silylenones
are accessed by a regioselective hydrosilylation of the ynone
precursor. The synthetic utility of these compounds is demon-
strated in cross-coupling reactions, highlighting the potential of
these protocols for the syntheses of geometrically defined trisub-
stituted olefins.
catalyst
(5 mol %)
solvent,
temp (°C)
Conversion isomer ratio
(Z:E)a
entry
time (h)
(%)a
1
2
3
4
5
6
7
8
PdCl2
PhCH3, 70
48
36
36
4
4
5
5
1
48
3.5
1.5
<5
<5
<5
<5
<5
-
-
CpRu(CH3CN)3PF6 PhCH3, 50
(Ph3P)3RuCl2
ZnCl2
ZnCl2
AuCl
PhCH3, 50
CH2Cl2, 23
PhCH3, 50
PhCH3, 50
PhCH3, 50
PhCH3, 40
PhCH3, 35
PhCH3, 50
PhCH3, 80
-
-
-
1.7:1
1:1.7
>19:1
-
6:1
10:1
b
100
100
b
The use of π-acidic metals, in particular complexes based on
gold and platinum, to render an alkyne functional group electrophilic
is a fundamental initiation step in a variety of chemical transforma-
tions.1 In general, this activation step is paired with attached
nucleophiles, such as alkenes, carbonyls, arenes, ethers, or strained
carbocycles, to bring about isomerization-based transformations.
We became curious as to whether the carbon-silicon bond, with
its intrinsic electron-rich nature, could act as a nucleophile in a
similar reactivity mode. Herein, we describe the realization of this
hypothesis with the PtCl2-catalyzed isomerization of R-hydrox-
ypropargylsilanes to R-silylenone products (e.g., 2 f 3, Table 1)
with high levels of (Z)-selectivity. In addition, we illustrate the
hydrosilylation of ynones, using the same PtCl2 catalyst, to provide
complementary geometrical selectivity. Lastly, we demonstrate the
synthetic utility of these enone products, establishing a convenient
method for the stereoselective synthesis of trisubstituted olefins.
In preliminary studies designed to ascertain the migratory aptitude
of trialkylsilyl groups toward activated alkynes, we targeted
R-hydroxypropargylsilanes such as 2 (Table 1)sit was expected
that alkyne activation would initiate an interaction between the
developing empty p-orbital and the proximal C-Si bond. These
compounds are readily accessible via an alkynylide addition into
an acylsilane, and a variety of R-hydroxypropargylsilanes were
accessed by this protocol.2 With substrates in hand, we began
examining their reactivity in the presence of potential alkyne
activators (Table 1). Although a number of these metal complexes
exhibited little to no reactivity, rearrangements to enone products
were observed when these silanes were treated with either gold or
platinum salts. Gold species effected complete consumption of the
propargylsilane (entries 6-8), but platinum-based isomerizations
ultimately provided similar reactivities and higher yielding reactions
(entries 9-11). Under optimized conditions (5 mol % PtCl2, toluene,
80 °C), R-silylenone 3 was produced in virtually quantitative yield
and with excellent stereoselectivity (ranging from 10:1 to >19:1
favoring the (Z)-isomer).3
AuCl3
[Au]/[Ag]
c
d
100(76 )
<5
100
9
10
11
PtCl2
PtCl2
PtCl2
d
100(99 )
a Measured by 1H NMR. b Significant quantities of protodesilylated
enones were observed. c [Au]/[Ag]: Chloro[2-(di-tert-butylphosphino)-
biphenyl]gold(I) (5 mol %) + AgSbF6 (20 mol %). d Isolated yield.
ineffective in the isomerization of the compounds studied here
(Table 1, entries 4, 5). One of the most pertinent comparisons is
the ruthenium-catalyzed redox isomerization of propargylic alcohols
to (E)-enones, originally reported by both Ma6 and Trost.7 The
transformation described herein is akin to this reaction but provides
additional functionality in the silicon group to allow for further
manipulation.
With the platinum-catalyzed method fully optimized, a number
of propargylsilanes were isomerized to the corresponding enones
in uniformly high yields and selectivities, even with markedly low
catalyst loadings (Table 2, entries 2, 4). More sterically hindered
alkynes (entry 6) were isomerized cleanly, albeit with longer
reaction times. Esters, carbamates, silyl ethers, acetals, and distal
olefins were all tolerated in this transformation. The overall reaction
times were particularly brief for substrates bearing propargylic ether
substituents that were potentially capable of precoordination (entries
12, 13). This transformation likely proceeds via an initial alkyne
coordination, followed by an anti-selective silyl migration to a
vinylplatinum species (Scheme 1). Protodemetalation leads to the
enone products with the observed stereochemistry.
Having selectively accessed a number of (Z)-silylenones via this
protocol, our efforts next turned to olefin isomerization studies to
Scheme 1
Analogous metal-induced silyl migration has been observed
previously in isolated cases. Schaumann reported examples of
similar migrations using zinc chloride to provide (E)-silylenones;
however, an acetylenic TMS group was required.4,5 ZnCl2 was
9
11926 J. AM. CHEM. SOC. 2010, 132, 11926–11928
10.1021/ja1058197  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Pt-Catalyzed Hydrosilylations of Ynones
Table 2. Pt-Catalyzed Rearrangements of R-Hydroxypropargylsilanes
a
Measured by H NMR. b Isolated yield. c Isolated as a mixture of R
1
and ꢀ isomers.
several investigations into alkylsilanes that are capable of generating
a Si-X intermediate in situ.16
In our studies, the benzyldimethylsilyl group appeared ideal for
the downstream generation of Hiyama coupling partners,16e its
robust nature likely to be compatible with formation of the
acylsilane precursor, the nucleophilic alkyne addition, and the
platinum-catalyzed isomerization. Indeed, R-silylenone 5 could be
formed from readily accessible alcohol 4, with the silyl migration
proceeding in excellent yield and stereoselectivity (Scheme 2).
Enone 5 was reduced, and the corresponding alcohol was evaluated
in representative Hiyama couplings.17 Gratifyingly, these reactions
provided the aryl alkenyl coupling products in good yield.18 (E)-
Silylenone 8 was also converted to the corresponding coupling
product, highlighting that these two complementary platinum-
catalyzed methods can be utilized in the syntheses of stereodefined
trisubstituted alkenes.19
b
a Isolated yield. Measured by H NMR. c 1 mol % PtCl2, 0.25 M in
1
PhCH3. d 2.5 mol % PtCl2, 0.2 M in PhCH3.
obtain the complementary (E)-silylenones. Attempts to achieve
selectivity, however, were met with limited success under a variety
of conditions.8 Interestingly, we found that a hydrosilylation
approach afforded these desired (E)-enone products.
Although metal-catalyzed hydrosilylation is a thoroughly studied
transformation,9 selectivities in the hydrosilylation of internal
alkynes remain comparatively less explored.10 By treatment with
the same PtCl2 catalyst and a silane in toluene at room temperature,
a number of ynones were hydrosilylated in good yields and largely
with excellent regio- and stereoselectivities (Table 3). The (Z)-
stereoselectivity is consistent with the Chalk-Harrod mechanism
frequently observed in Pt-catalyzed hydrosilylations;11 the observed
regioselectivity can be attributed to an electronic effect, wherein
the metal center resides R to the carbonyl in the hydroplatinated
intermediate.12 Importantly, this transformation consistently pro-
vides the opposite geometrical isomers to those formed in the silyl
migration process.13
To summarize, we have described a platinum-catalyzed isomer-
ization of R-hydroxypropargylsilanes. The transformation proceeds
Scheme 2
With efficient protocols for accessing the above silylenone
products, our efforts were then directed toward investigating the
overall synthetic utility of these compounds.14 The Hiyama coupling
is an attractive method for the formation of sp2-sp2 carbon-carbon
bonds,15 particularly because the inherent stability of the vinylsilane
nucleophiles allows them to be carried through multiple synthetic
steps. In general, silanes with attached heteroatomic moieties (e.g.,
alkoxysilanes) are required for reactivity in these cross-couplings,
but alkoxysilanes are typically more unstable than their alkylsilane
counterparts. Motivated by these circumstances, there have been
9
J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 11927

C O M M U N I C A T I O N S
(10) For a recent discussion, see: Trost, B. M.; Ball, Z. T. Synthesis 2005, 853–
887.
in good to excellent yield with a high degree of geometrical
selectivity for a range of substrates. The substrates are readily
accessible via alkyne-based nucleophilic additions into acylsilanes,
this method representing a straightforward option for convergent
fragment coupling. The PtCl2-catalyzed hydrosilylations of the
corresponding ynones, also accessible via alkyne-based nucleophilic
additions, provide complementary geometry in these enone prod-
ucts.20 Finally, we have demonstrated the synthetic utility of the
observed silylenones, validating that the vinylsilane provides a
functionality for further manipulations. The formation of geo-
metrically pure trisubstituted olefins remains a challenge in synthetic
chemistry; the methods herein provide operationally simple pro-
tocols for accessing these structural motifs. Further explorations
of these unique transformations and applications will be reported
in due course.
(11) Chalk, A. J.; Harrod, J. F. J. Am. Chem. Soc. 1965, 87, 16–21.
(12) Most hydrosilylation studies of internal alkynes have achieved regioselec-
tivities primarily through either steric discrimination or intramolecular
delivery of tethered silanes. For catalytic regioselective hydrosilylations
of internal alkynes apparently reliant on electronic differentiation, see: (a)
Hamze, A.; Provot, O.; Alami, M.; Brion, J.-D. Org. Lett. 2005, 7, 5625–
5628. (b) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2005, 127, 17644–
17655. (c) Konno, T.; Taku, K.-i.; Yamada, S.; Moriyasu, K.; Ishihara, T.
Org. Biomol. Chem. 2009, 7, 1167–1170. (d) Tius has described a rhodium-
catalyzed hydrosilylation of ynals to provide similar R-selectivity to our
system, but steric differentiation was also highly influential. See: Tius,
M. A.; Pal, S. K. Tetrahedron Lett. 2001, 42, 2605–2608.
(13) Although geometrical considerations are not applicable, it should be noted
that substrates based on terminal alkynes were effective in the silyl migration
process but provided complex mixtures in the hydrosilylation process. See
Supporting Information for details.
(14) For a review of the use of R-substituted enones in cross-coupling reactions,
see: Negishi, E.-i. J. Organomet. Chem. 1999, 576, 179–194.
(15) For select reviews, see: (a) Denmark, S. E.; Liu, J. H.-C. Angew. Chem.,
Int. Ed. 2010, 49, 2978–2986. (b) Denmark, S. E.; Sweis, R. F. In Metal
Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich,
F., Eds.; Wiley-VCH: Weinheim, 2004; Chapter 4. (c) Hiyama, T. In Metal
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, 1998; Chapter 10 and references therein.
(16) (a) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821–5822.
(b) Itami, K.; Nokami, T.; Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida,
J.-i. J. Am. Chem. Soc. 2001, 123, 11577–11585. (c) Hosoi, K.; Nozaki,
K.; Hiyama, T. Chem. Lett. 2002, 31, 138–139. (d) Nakao, Y.; Oda, T.;
Sahoo, A. K.; Hiyama, T. J. Organomet. Chem. 2003, 687, 570–573. (e)
Trost, B. M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5, 1895–1898.
(f) Anderson, J. C.; Munday, R. H. J. Org. Chem. 2004, 69, 8971–8974.
(g) Nakao, Y.; Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T. J. Am.
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Acknowledgment. Colorado State University is acknowledged
for support. We also thank Professors Kennan, Rovis, Shi, Williams,
Wood, and their respective research groups for both sharing supplies
and helpful discussions.
Supporting Information Available: Experimental procedures,
compound characterization data, and spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
(17) The silylenone products were not effective Hiyama coupling partners, likely
due to the complicating electrophilicity of the enone under the fluoride-
based conditions.
(18) Water additive was crucial to the success of these transformations, most
likely facilitating the formation of a disiloxane intermediate which upon
fluoride activation is the active transmetallation species. For a relevant
discussion, see: Denmark, S. E.; Sweis, R. F.; Wehrli, D. J. Am. Chem.
Soc. 2004, 126, 4865–4875.
(19) R-Silylenones can also be converted to R-iodoenones by treatment with
ICl; see: Alimardanov, A.; Negishi, E.-i. Tetrahedron Lett. 1999, 40, 3839–
3842. (b) This process is generally stereoconvergent, however, as illustrated
in the transformations of both 3 and 10 to 11. In contrast, the use of Hiyama
couplings enables efficient access to both isomers of the trisubstituted
alkenes.
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