Ethylene transposition: Ruthenium hydride catalyzed intramolecular trans -silylvinylation of internal alkynes

Article abstract of DOI:10.1021/ol5020027

A highly selective intramolecular trans-silylvinylation of internal alkynes catalyzed by RuHCl(CO)(SIMes)(PPh₃) has been accomplished. The use of methyl vinyl ketone as an additive increased the efficiency of this transformation. This process w

Full text of DOI:10.1021/ol5020027

Letter
pubs.acs.org/OrgLett
Ethylene Transposition: Ruthenium Hydride Catalyzed
Intramolecular trans-Silylvinylation of Internal Alkynes
Shasha Liu,‡ Jinbo Zhao,‡ Lauren Kaminsky, Robert J. Wilson, Nadia Marino,§ and Daniel A. Clark*
Department of Chemistry, 1-014 Center for Science and Technology, Syracuse University, Syracuse, New York 13244, United States
S
* Supporting Information
ABSTRACT: A highly selective intramolecular trans-silylvinylation of internal
alkynes catalyzed by RuHCl(CO)(SIMes)(PPh3) has been accomplished. The
use of methyl vinyl ketone as an additive increased the efficiency of this
transformation. This process was used to successfully form five-, six-, and seven-
membered oxasilacycles by a formal anti-exo-dig cyclization.
ilicon tethers are widely applicable in organic synthesis,
having found uses in a variety of reactions including
acrylates to give highly substituted dienes. Unlike the
aforementioned reactions, this process affords the trans-isomer
selectively, a rare example of an intramolecular trans-
substitution across an alkyne.15,30,31
S
metathesis, cross-coupling, carbocyclization, and hydro- and
carbosilylation. Their use to create highly functionalized
systems in a regio- and stereodefined manner has spurred
renewed interest of late.1 In addition to being highly selective,
these reactions create complex silanes which offer a versatile
functional handle for further manipulation.2 The majority of
work in this area has focused on hydrosilylation chemistry.3−7
Recently, a number of ruthenium catalyzed protocols have
emerged for the synthesis of trisubstituted olefins using an
intramolecular hydrosilylation of alkynes.8−15 These comple-
mentary routes to trisubstituted vinylsilanes are inherently
limited due to the mandatory inclusion of a hydrogen atom into
the product alkene. Subsequent studies on silylcarbonylation
and silylcyanation16 of alkynes have been described to
circumvent this limitation.17−20 Specifically, Ojima and Den-
mark have studied the silylformylation of alkynes and found
that five- and six-membered rings could be formed readily in
this reaction.21−25 Silylformylation and silylcyanation reactions
afford the syn-alkene isomers selectively. Intermolecular
versions of silylcarbocyclization reactions also afford the syn-
isomers.26−28 We have recently reported that vinyl-silicon
tethers can be used to control both the regio- and
stereochemistry in the silylvinylation of pendent alkynes with
acrylates.29 The subsequent vinyl ruthenium species intercept
While examining catalysts for this transformation, we
discovered that ruthenium hydride complex 5 gave a nearly
1:1 mixture of acrylate product 2a and vinylation product 3a. A
careful examination of the product indicated, as previously
observed with the acrylate products, that the anti-5-exo-dig
isomer was obtained. Given the novelty of this transformation,
we set out to find an optimized protocol for the synthesis of
vinylated product 3a. Simply adding alkyne 1a in DCE and
hydride 5 to a sealed tube and heating to 85 °C overnight gave
a 70% conversion of the starting material. Under these
conditions, we observed a mixture of the expected vinylated
product 3a and diene 4a (Table 1). Cycloisomerization of
substituted enyne compounds with ruthenium hydrides has
been reported previously.32 These compounds were separated
by column chromatography, and NOE experiments confirmed
the assigned stereochemistry shown.33
Specifically, irradiation of the internal vinyl proton (at C2)
displayed an enhancement of both diastereotopic allylic protons
(at C5) in the oxasilylcyclopentane ring. Also, NOESY data
displayed cross-peaks for the silylmethyl groups and protons on
the aromatic ring.
Our previous results indicated full consumption of 1a in only
9 h; thus, we theorized that the acrylate may play a beneficial
role in the reaction.29 Therefore, we screened electron-deficient
olefins as additives in this reaction. As shown in Table 1, methyl
methacrylate and acrylonitrile were beneficial to the reaction
affording 50% and 55% conversion of the starting material,
respectively (entries 2−3). No reaction was observed with
phenylvinylsulfone as an additive (entry 4). Pleasingly,
vinylphosphonates and acrylamides afforded a good conversion
1
and high yield by H NMR (entries 5−7). Moreover, acyclic
vinylketones afforded a full conversion and high yield of the
product with an excellent ratio of 3A to 4A (entry 8). The use
Received: July 9, 2014
© XXXX American Chemical Society
A
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Letter
In a 1:1 ratio of MVK to catalyst 5, an 83% conversion was
attained in only 5 h. Addition of 10 mol % MVK provided the
best results for both the yield and ratio of 3a:4a. Additional
MVK showed no further beneficial effect at a 5 mol % loading
of complex 5. Interestingly, it was found that the loading of
complex 5 could be lowered provided the concentration of
MVK was kept high. This of course came at the expense of the
reaction time. Our current hypothesis is that the MVK protects
the ruthenium catalyst from decomposition.32,35
Table 1. Screen of Additives
Next, we examined the substrate scope of this reaction
(Figure 1). Use of 5 mol % catalyst 5 and 10 mol % MVK was
implemented in an attempt to keep the reaction time less than
24 h. Alkynes bearing a phenyl group at the terminus were
examined first. Dienes 3a−3f were produced from the
corresponding phenyl alkynes. These substrates performed
admirably, providing reaction products in good yields with 3 to
4 ratios consistently between 5:1 and 10:1 for compounds 3a−
3f (ratios in parentheses). Both electron-rich functionality as in
the case of the anisole substituted diene 3g and electron-
withdrawing acetyl and nitro groups on the aryl ring were well
tolerated. Crystallization of compound 3j allowed for
unambiguous verification of its structure through X-ray
diffraction. As anticipated from NOESY experiments, the
structure of 3j is as depicted in Figure 1. All other structures
have been determined through NOESY experiments or by
analogy. Compound 3h which bears a fluorine moiety was
prepared in 71% yield. Methyl groups were also tolerated at the
3 and 5 positions and provided diene 3k in 73% yield. Bulky
groups at the ortho position such as chlorine were well
tolerated and afforded 3l in 73% yield while the 1-naphthyl
analogue 3m was provided in 63% yield. These structures (3l
and 3m) appear as mixtures of atropisomers by proton NMR.
Substrates 1p and 1q which possess both propargylic and
homopropargylic functionality provided >15:1 ratios favoring
products 3p and 3q in 64% and 65% yield, respectively. Six-
membered silylcycles could also be formed efficiently regardless
of Thorpe−Ingold factors.36 Compounds 3r and 3s were
obtained in 59% and 74% yields, respectively. Of note, seven-
membered ring product 3t was formed in 53% yield using this
methodology. Ojima et al. have noted the formation of seven-
membered rings using rhodium catalyzed silylformylation
provides a mixture of products with only trace amounts of
a
1
Yield based on remaining 1a by H NMR versus mesitylene internal
b
1
standard. Ratio of 3a and 4a was determined by H NMR versus
mesitylene internal standard. 3a was obtained as a mixture of isomers
(10:1, Z/E) as observed by H NMR.
c
1
of cyclohexanone as an additive suggests that η-4-coordination
of the additive may not be a requirement (entry 9). We also
examined using ethylene (entry 10); however, a mixture of
inseparable stereoisomers of 3a were obtained. Methyl vinyl
ketone (MVK) was chosen as our additive, as it provided the
highest ratio of 3a to 4a, and its volatility facilitated removal of
the additive from the reaction mixture.
Examination of other ruthenium hydride complexes revealed
that complex 5 was particularly well suited for this reaction.34
Attempts to generate complex 5 in situ from commercially
available RuHCl(CO)(PPh3)3 and SIMes·HCl completely
failed. No conversion of 1a was observed after 24 h indicating
that 5 may not have formed under the reaction conditions. To
further optimize this reaction, the catalyst loading was
scrutinized; in particular, the amount of 5 in relation to MVK
was analyzed (Table 2). As previously mentioned, exclusion of
MVK from the reaction gave only a 70% conversion after 24 h.
37,38
1
the desired product observable by H NMR and GC-MS.
In this case, the corresponding eight-membered ring was not
1
observed in the H NMR of the crude reaction mixture.
Table 2. Optimization for Silylvinylation Product 3a
In our previous investigations alkyl groups at the alkyne
terminus provided trans-silylvinylated products.29 Evaluation of
alkyl bearing alkyne substrates in the ethylene transposition
reaction was also undertaken. Alkyne 1u was subjected to
conditions previously utilized for ethylene transposition; to our
surprise, this led to the formation of 4u as the sole product in
82% yield (Table 3). Alkyne 1v, which also possesses a tert-
butyl substituent, afforded 4v in 66% isolated yield. Concerned
that this switch in reactivity was due to sterics arising from the
bulky tert-butyl group, we investigated methyl substituted
alkynes. Under analogous conditions we again observed only
cycloisomerization product 4w in 72% yield by 1H NMR (66%
isolated yield) and 4x in 59% isolated yield. Given the similar
steric impediment of the alkyne methyl versus the propargylic
methylene in 1w and 1x we surmise that this change in
reactivity cannot be caused solely by steric congestion.
Cycloisomerization products from tethered enynes have been
reported by Mori in the presence of ruthenium hydrides.32,39
hydride 5
(mol %)
MVK
(mol %)
time
(h)
conversion
(%)
ratio
entry
(3a:4a)
1
2
3
4
5
6
7
8
5
none
5
24
5
70
53:17
55:09
85:15
68:11
22:10
88:12
6:13
5
83
5
10
20
5
5
100
98
5
5
2.5
2.5
1
24
24
48
48
46
25
2
100
27
1
25
91
76:8
B
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Letter
a
b
Figure 1. Scope of silylvinylation with aryl-substituted alkynes.a,b Yields represent only isolated vinylation products 3. Ratios in parentheses
1
c
represent the ratio of vinylation product 3 to cycloisomerization product 4 as determined by H NMR of the crude reaction mixture. Structure
verified by X-ray crystallography.
Table 3. Diene Formation with Alkyl-Substituted Alkynes
Scheme 1. Derivatization of Diene 3a
product 6 in 84% yield. Addition of methyl lithium to 3a
provided alcohol 7 in 73% yield. Selective hydrogenation of the
terminal olefin in diene 3a provided tetrasubstituted olefin 8 in
near quantitative yield. Finally, olefin metathesis of 3a provided
diene 9 in 55% yield using 1-octene, and diene 10 in 53% yield
using ethyl acrylate as a cross partner. Both diene moieties were
isolated as a single isomer by 1H NMR. The silylvinylation and
metathesis reaction can also be performed in tandem to afford
similar overall yields.
In summary, we have demonstrated an effective protocol for
a formal anti-exo-dig silylvinylation of internal alkynes. The
reaction was amenable to various aryl alkynes and the diene
products were further functionalized to afford tetra substituted
olefins. Alkyl substituted alkynes afforded 1,3-dienes possibly
through cycloisomerization. Further studies on mechanism,
We are currently investigating the factors determining this
switch in product formation, as well as related methods for the
synthesis of dienes such as 3u−x and 4a−t using ruthenium
catalysis.
Synthetic utility of the silylvinylation products was
demonstrated using representative example 3a (Scheme 1).
Fluoride mediated removal of silicon afforded hydrovinylation
C
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(23) Denmark, S. E.; Liu, J. H.-C. J. Am. Chem. Soc. 2007, 129, 3737−
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76, 201−215.
ASSOCIATED CONTENT
■
(25) Denmark, S. E.; Liu, J. H.-C.; Muhuhi, J. M. J. Am. Chem. Soc.
2009, 131, 14188−14189.
S
* Supporting Information
(26) Foley, C. N.; Leighton, J. L. Org. Lett. 2014, 16, 1180−1183.
(27) Leighton, J. L. Stereoselective Rhodium(I)-Catalyzed Hydro-
formylation and Silylformylation Reactions and Their Application to
Organic Synthesis. In Modern Rhodium-Catalyzed Organic Reactions;
Wiley-VCH Verlag GmbH & Co. KGaA: 2005; pp 93−110.
(28) O’Malley, S. J.; Leighton, J. L. Angew. Chem., Int. Ed. 2001, 40,
2915−2917.
Experimental procedures and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: daclar01@syr.edu.
Author Contributions
‡S.L. and J.Z. contributed equally.
Notes
(29) Zhao, J.; Liu, S.; Marino, N.; Clark, D. A. Chem. Sci. 2013, 4,
1547−1551.
(30) Matsuda, T.; Kadowaki, S.; Yamaguchi, Y.; Murakami, M. Chem.
Commun. (Cambridge, U. K.) 2008, 24, 2744−2746.
(31) Matsuda, T.; Yamaguchi, Y.; Shigeno, M.; Sato, S.; Murakami,
M. Chem. Commun. (Cambridge, U. K.) 2011, 47, 8697−8699.
(32) Nishida, M.; Adachi, N.; Onozuka, K.; Matsumura, H.; Mori, M.
J. Org. Chem. 1998, 63, 9158−9159.
(33) We have noted that many of the cycloisomerization compounds
readily decompose when exposed to silica gel chromatography. The
ratios are reported for crude reaction mixtures that were plug filtered
through silica gel.
(34) See Supporting Information for details of catalyst screen.
(35) Giessert, A. J.; Brazis, N. J.; Diver, S. T. Org. Lett. 2003, 5,
3819−3822.
(36) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105, 1735−1766.
(37) Ojima, I.; Tzamarioudaki, M.; Tsai, C.-Y. J. Am. Chem. Soc.
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The authors declare no competing financial interest.
§Please send correspondence regarding X-ray crystal structure
data to Dr. Nadia Marino (nmarino@syr.edu).
ACKNOWLEDGMENTS
■
We are grateful to the donors of the ACS PRF (DNI 50787),
the NSF (CAREER CHE-1352432), and Syracuse University
for generous financial support. We thank the Chisholm and
Totah research groups (Syracuse University) for copious
sharing of chemicals, instrumentation, and pertinent discus-
sions. We thank Prof. John Chisholm, for critically reading this
manuscript.
(38) Ojima, I.; Vidal, E.; Tzamarioudaki, M.; Matsuda, I. J. Am. Chem.
Soc. 1995, 117, 6797−6798.
(39) Mori, M.; Kozawa, Y.; Nishida, M.; Kanamaru, M.; Onozuka, K.;
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