Directing group-controlled hydrosilylation: Regioselective functionalization of alkyne

Article abstract of DOI:10.1021/ja209553f

Pt(0)-catalyzed hydrosilylation of unsymmetric alkynes proceeds in a highly regioselective manner with a dimethylvinylsilyl (DMVS) group as the directing group. This hydrosilylation affords a single regioisomer of silylalkenes from propargylic and homopro

Full text of DOI:10.1021/ja209553f

Communication
pubs.acs.org/JACS
Directing Group-Controlled Hydrosilylation: Regioselective
Functionalization of Alkyne
Yuuya Kawasaki,‡ Youhei Ishikawa,‡ Kazunobu Igawa,† and Katsuhiko Tomooka*,†
†Institute for Materials Chemistry and Engineering and ‡Department of Molecular and Material Sciences, Kyushu University, Kasuga,
Fukuoka 816-8580, Japan
S
* Supporting Information
Scheme 1. Regioselective Hydrosilylation Using a Directing
Group
ABSTRACT: Pt(0)-catalyzed hydrosilylation of unsym-
metric alkynes proceeds in a highly regioselective manner
with a dimethylvinylsilyl (DMVS) group as the directing
group. This hydrosilylation affords a single regioisomer of
silylalkenes from propargylic and homopropargylic alcohol
derivatives. DMVS also has an accelerating effect that
allows group-selective hydrosilylation of the DMVS-
attached alkyne prior to that of other alkynes. Combined
hydrosilylation and transformation reactions of the
resulting silylalkenes afford various tri-substituted alkenes
and multi-oxy-functionalized compounds with high
regioselectivity from unsymmetric alkynes.
he importance of transformation reactions of alkynes in
Torganic synthesis is undisputed, and various methods have
been developed to introduce functional groups to sp carbons of
alkynes.1 Among them, Pt(0)-catalyzed hydrosilylation is a
well-established reaction2 that provides E-silylalkene, a versatile
precursor for tri-substituted alkenes, ketones, acyloins, etc.3−6
The difficulty of regiocontrol in the hydrosilylation, however,
has prevented its application to an unsymmetric alkyne system
novel approach to achieve regioselective hydrosilylation and the
synthetic value of the resulting silylalkenes.
We first performed the hydrosilylation of propargylic alcohol
derivatives.14 The requisite DMVS ether 3a was prepared from
alcohol 2 by reaction with commercially available DMVSCl in
the presence of imidazole (eq 2). DMVS ether 3a was isolated
to obtain a mixture of regioisomers of A and B, as shown in eq
1.7,8
To address this problem, we planned to introduce a directing
group (DG) into a substrate to control the regioselectivity of
the hydrosilylation in an unsymmetric alkyne system (Scheme
1). In this approach, it is most important to select a DG that
can coordinate with the Pt(0) catalyst to adequately restrict the
reaction pathway. After several attempts, we found that a
dimethylvinylsilyl (DMVS) group, a substructure of the
Karstedt catalyst, [Pt(0)-1,1,3,3-tetramethyl-1,3-divinyldisilox-
ane] (1),9 is an excellent DG for proximal-selective hydro-
silylation of alkynes.10−13 Herein, we provide the details of our
in 98% yield as a sufficiently pure form after purification using
Celite column chromatography,15 even though we observed
partial hydrolysis of DMVS ether after purification using silica
gel column chromatography. Hydrosilylation of 3a was
performed with i-Pr3SiH at 80 °C in the presence of 1 (0.2
Received: October 11, 2011
Published: December 5, 2011
© 2011 American Chemical Society
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Communication
mol%) without solvent, followed by TBAF treatment to remove
DMVS. As expected, the reaction provided the proximal-
silylated product 4a in excellent yield (94%) with no trace of the
distal product 5a (proximal:distal = >99:<1).16−18
10a,b afforded exclusively proximal products 11a,b in 98% and
79% yield, respectively (eq 4).
Similar reactions using solvents at a concentration of 0.2 M,
such as THF, hexane, toluene, dioxane, and 1,2-dichloroethane,
also afforded 4a exclusively in excellent yields (88−95%)
without a significant decrease in the reaction rate.19 Moreover,
hydrosilylation of 3a using Et3SiH, i-Pr2ClSiH, and (EtO)3SiH
proceeded with excellent proximal selectivity (proximal:distal =
>99:<1, 77−87% yields). This flexibility in choosing the
hydrosilane is highly advantageous compared with the intra-
molecular variant.7a−c
In sharp contrast to the reaction of 3a, hydrosilylation of the
parent alcohol 2 and other ether derivatives 6−9 afforded E-
silylalkenes as a mixture of regioisomers, proximal:distal =
57:43−67:33 (Scheme 2). These results clearly indicate that
Even when DMVS was placed three carbons away from the
alkyne, hydrosilylation of the bis-homopropargylic alcohol
derivative 13 proceeded in a proximal-selective manner, albeit
with moderate selectivity (proximal:distal = 78:22) (eq 5).
Scheme 2. Hydrosilylation of Propargylic Alcohol 2 and Its
a
Derivatives 6−9 (R = C3H6Ph)
To clarify the origin of the observed high regioselectivity of
hydrosilylation, we formed hypotheses regarding the reaction
pathway and transition-state models. It is well accepted that the
regioselectivity of hydrosilylation with a Pt(0) catalyst is
determined at the hydroplatination step.20,21 Therefore, the
regioselectivity of the present hydrosilylation might also occur
at the hydroplatination step, in which a Pt center properly
coordinates with a vinyl moiety of DMVS. Based on these
hypotheses, transition-state models TS1 and TS2 are probable,
providing the proximal product and distal products, respectively
(Scheme 3). Comparison of both models indicated that TS2 is
a
Reagents and conditions: i-Pr3SiH (1.0 equiv), 1 (0.2 mol%), 80 °C.
b
c
Combined yield of the proximal- and distal-silylated products. Ratio
of proximal- and distal-silylated products (proximal:distal).
Scheme 3. Proposed Reaction Mechanism for
Hydrosilylation of DMVS Ethers
DMVS is highly capable of controlling the regioselectivity of
Pt(0)-catalyzed hydrosilylation in an unsymmetric alkyne
system.
Hydrosilylation of other DMVS ethers 3b−f, which were
prepared from propargyl alcohol (R1 = H, R2 = H), 2-butyn-1-
ol (R1 = Me, R2 = H), 3-cyclohexyl-2-propyn-1-ol (R1 = c-Hex,
R2 = H), 4,4-dimethyl-2-pentyn-1-ol (R1 = t-Bu, R2 = H), and a
secondary propargylic alcohol (R1 = C3H6Ph, R2 = Me),
respectively, also afforded proximal-silylated allylic alcohols
4b−f as the sole product in excellent yield (84−92%),
irrespective of steric hindrance at the proximal and distal
positions of the alkyne carbons (eq 3). Therefore, the present
disfavored by the highly strained ring structure; hence,
hydrosilylation would proceed via the less strained TS1 to
afford the proximal-silylated product.
To probe this potential mechanism further, we performed a
DFT computational study of the reaction of 3c with Me3SiH as
a model (Scheme 4).22 Initially, a TS1-type transition state, TSa,
was computed, and then an intrinsic reaction coordination
calculation of TSa was performed to analyze the reaction
pathway.23 The results revealed that the starting intermediate
IMa overcame the energy barrier of TSa (+10.7 kcal/mol) while
maintaining the chelation structure. TSa converted to the
proximal-hydroplatination product IMb with a decrease in
energy of 6.6 kcal/mol from IMa. The calculated results
supported the observed proximal selectivity of the hydro-
silylation.
method complements the previously developed methods with
regard to regioselectivity, particularly in a terminal alkyne
system.
The developed DMVS method is also efficient in the
homopropargylic system. Hydrosilylation of DMVS ethers
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a
Scheme 4. Reaction Pathway Analysis of Hydrosilylation in
the DMVS Ether System Using DFT Calculation
Scheme 5. Transformation of 3a Using Hydrosilylation
a
Reagents and conditions: (a) i-Pr2ClSiH (1.0 equiv), 1 (0.2 mol%),
a
Relative zero-point energies (ΔE0) based on IMa in kcal/mol.
80 °C; (b) K2CO3, H2O, THF, rt; (c) PhI (1.0 equiv), TBAF,
Pd2(dba)3·CHCl3 (5 mol%), THF, rt; (d) (EtO)3SiH (1.0 equiv), 1
(0.2 mol%), 80 °C; (e) H2O2, NaHCO3, THF−MeOH, 50 °C.
The DMVS acts not only as the DG but also as the
accelerating group for the hydrosilylation. For example,
hydrosilylation of a 1:1:1 mixture of DMVS ether 3a, alkyne
16 (R′ = C3H6Ph), and i-Pr3SiH afforded products from 3a and
16 in 93% and 2% yield, respectively, indicating that
hydrosilylation of 3a proceeds 46.5 times faster than that of
16 (Table 1, entry 1).24 Furthermore, DMVS ether 3a reacts
Tamao’s condition converted 3a to the acyloin product 24
(77% yield in two steps) exclusively.27
Furthermore, the current hydrosilylation combined with our
previously reported addition-type ozone oxidation produces
poly-oxy-functionalized compounds regioselectively.5 For ex-
ample, DMVS ether 25, easily available from 2-butyne-1,4-diol,
was converted to silylalkene 26 by hydrosilylation with i-Pr3SiH
(eq 6, 99% yield, proximal:distal = >99:<1). After TBS
Table 1. Competitive Experiments on Hydrosilylation
between 3a and Other Alkynes
etherification, ozone oxidation of the thus-obtained silylalkene
27 in AcOEt at −78 °C afforded the α-silylperoxy ketone 28
with different oxy-functional groups on all four carbons in 81%
yield.28,29
In summary, we described a highly regioselective Pt(0)-
catalyzed hydrosilylation of unsymmetric alkynes using DMVS
as a directing group. The novel sequential conversion of alkynes
via hydrosilylation and transformations of the resulting E-
silylalkene moiety is an efficient approach to the synthesis of
versatile multi-substituted alkenes and oxy-functionalized
compounds. Further studies toward expanding the present
directing group method for other reactions and their
applications are in progress.
a
b
Determined by GLC analysis. Isolated yields of the corresponding
alcohols after TBAF treatment of the hydrosilylation products.
c
1
Determined by H NMR analysis.
∼8 and 5 times faster than TBS ether 7 (R′ = CH2OTBS) and
the DMVS ether of homopropargylic alcohol 10a (R′ =
C2H4ODMVS), respectively (Table 1, entries 2 and 3).25 The
significant acceleration effect of DMVS on the propargylic
alcohol 3a is most likely due to preferential chelation with the
Pt center, as proposed in Scheme 4.
The reported hydrosilylation offers an efficient approach to
the synthesis of highly functionalized alkenes and ketones with
regioselective introduction of functional groups to the
unsymmetric alkynes. For examples, 3a can be converted to
tri-substituted Z-alkene 22 without the formation of any other
isomers via hydrosilylation with i-Pr2SiClH, followed by
hydrolysis of the chlorosilane moiety to silanol 21 (82% yield
in two steps) and the Hiyama coupling reaction with
iodobenzene (87% yield) (Scheme 5).26 On the other hand,
hydrosilylation with (EtO)3SiH followed by oxidation using
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
ktomooka@cm.kyushu-u.ac.jp
ACKNOWLEDGMENTS
■
This research was supported in part by MEXT, Japan [Grant-
in-Aid for Scientific Research on Innovative Areas (Project No.
2105: Organic Synthesis Based on Reaction Integration),
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Chem. Soc. 1974, 96, 3684. (b) Metz, P.; Linz, C. Tetrahedron 1994,
50, 3951.
(12) Brookhart et al. reported Co-catalyzed intramolecular hydrogen
transfer from an amine moiety to a DMVS group and proposed that
DMVS acts as a DG: Bolig, A. D.; Brookhart, M. J. Am. Chem. Soc.
2007, 129, 14544.
Global COE Program (Kyushu Univ.), and MEXT Project of
Integrated Research on Chemical Synthesis], and Industrial
Technology Research and Development Project (No.
09C46622a) from NEDO, Japan. We thank Y. Tanaka
(IMCE, Kyushu Univ.) for HRMS measurements.
(13) Jamison et al. reported alkene-directed coupling reactions of
enyne and aldehyde using Ni catalyst: (a) Miller, K. M.;
Luanphaisarnnont, T.; Molinaro, C.; Jamison, T. F. J. Am. Chem.
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(14) It is recognized that regiocontrol of hydrosilylation of
propargylic alcohol derivatives is difficult, even with an intramolecular
variant system. Pt-catalyzed intramolecular hydrosilylation of hydro-
silyl ethers derived from propargylic alcohols does not afford the
corresponding four-membered cyclic silylalkenes owing to its strained
structure. To solve this problem, Denmark et al. developed disiloxane-
tethered intramolecular hydrosilylation of propargylic alcohol
derivatives.7c
(15) Removal of concomitantly produced imidazole hydrochloride
salt by Celite column chromatography is important to achieve the high
regioselectivity of the hydrosilylation of DMVS ethers.
(16) The DMVS group of 3a was intact after hydrosilylation. In fact,
1H NMR analysis of the crude products of hydrosilylation confirmed
that there was no trace of products missing the vinyl moiety on
DMVS.
(17) We also observed partial hydrolysis of DMVS of the
hydrosilylation products during purification using silica gel chroma-
tography. To avoid confusion, purifications were performed after
removal of DMVS.
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́
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́
́
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