Zinc(II) catalyzed conversion of alkynes to vinyl triflates in the presence of silyl triflates

Article abstract of DOI:10.1021/ol501852n

The conversion of alkynes to their corresponding vinyl triflates in the presence of stoichiometric TMS-triflate was greatly facilitated by the triflate salt of several transition metal catalysts most especially Zn(OTf)₂. Products are formed in high regioselectivity under mild conditions. Internal alkynes bearing an aryl substituent afford vinyl triflates with a modest preference for the Z-isomer especially with larger substituents. A mechanism is put forward to explain the unique role of silicon in this system.

Full text of DOI:10.1021/ol501852n

Letter
pubs.acs.org/OrgLett
Open Access on 07/25/2015
Zinc(II) Catalyzed Conversion of Alkynes to Vinyl Triflates in the
Presence of Silyl Triflates
Mohammed H. Al-huniti and Salvatore D. Lepore*
Department of Chemistry, Florida Atlantic University, Boca Raton, Florida 33431-0991, United States
S
* Supporting Information
ABSTRACT: The conversion of alkynes to their correspond-
ing vinyl triflates in the presence of stoichiometric TMS-triflate
was greatly facilitated by the triflate salt of several transition
metal catalysts most especially Zn(OTf)2. Products are formed
in high regioselectivity under mild conditions. Internal alkynes
bearing an aryl substituent afford vinyl triflates with a modest preference for the Z-isomer especially with larger substituents. A
mechanism is put forward to explain the unique role of silicon in this system.
inyl triflates continue to play an important role in organic
synthesis most especially in C−C bond formation using
Scheme 1. Strategy for Metal Catalyzed Alkyne Conversion
to Vinyl Triflate
V
palladium-catalyzed coupling reactions.1 These intermediates
are usually produced by trapping ketone enolates with various
trifluoromethanesulfonylating agents.2 Fewer methods exist for
their formation from alkynes. Early efforts involved the addition
of trifluoromethanesulfonic acid (triflic acid) to an alkyne.3
Besides the highly acidic conditions, the method suffers from
several drawbacks including the requirement of very low
temperatures (−100 °C) and exacting workup conditions to
prevent isomerization. In some cases, the use of excess alkyne is
required.4 Additions of sulfonic acids to alkynes in the presence
of Au5 and Rh6 have also been reported to give the E-isomer as
a major product. Very recently, the formation of vinyl triflates
using diaryl iodonium triflate reagents under mild conditions
was reported independently by Gaunt7 and Liu.8 In these
methods, the iodonium reagent donates its aryl ligand to the
substrate providing an excellent route to tri- and tetra-
substituted alkenes. In seeking a strategy to form vinyl triflates
from alkynes without ligand transfer, we were inspired by
recent reports that vinyl triflates were formed as intermediates
in iridium and iron catalyzed alkyne hydrations.9 There is also
evidence that vinyl triflates can be obtained from aryl alkynes
and trimethylsilyl triflate (TMSOTf) albeit under fairly harsh
conditions and lengthy reaction times.10
Finally, a report by Rahaim and Shaw demonstrated that
TMSOTf reacts with terminal alkynes to give alkynyl-TMS
products in the presence of an amine base.11 In examining this
and previous reports, we suspected that Shaw’s method
involved the intermediacy of vinyl triflate B (Scheme 1). We
have previously observed the propensity of vinyl triflates to
produce alkynes in the presence of mild amine bases.12 Thus,
we reasoned that the absence of base should make possible the
formation of vinyl triflates (Scheme 1). Indeed, as described
here, we found that alkynes react with TMSOTf to rapidly
afford vinyl triflates under exceptionally mild conditions in the
presence of a variety of transition metal salts.
transformation required 48 h at room temperature in
acetonitrile to achieve 80%−90% conversion. This same
reaction in the presence of 10% Cu(OTf)2 afforded 1a in
75% conversion in 1 h (Table 1, entry 1).
Table 1. Screening of Metal Catalysts and Silyl Reagents
a
silyl-OTf
(equiv)
react time
(min)
conv
(%)
entry
catalyst
silyl
1
Cu(OTf)2
Cu(OTf)2
CuI
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
Et3Si
1.0
1.5
1.0
1.5
1.0
1.5
1.5
1.5
1.5
1.5
1.5
1.5
60
50
75
90
53
67
74
76
43
68
91
76
64
2
3
60
4
CuI
50
5
CuOTf
60
6
CuOTf
50
7
Sc(OTf)3
Rh[COD]2Cl2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
50
8
20
9
20
10
11
12
210
600
1440
iPr3Si
b
Zn(OTf)2
tBu2PhSi
53
a
b
1
Determined by H NMR. Reaction incomplete after 24 h.
We initially studied the conversion of phenyl acetylene (1) to
Received: June 26, 2014
vinyl triflate 1a in the presence of TMSOTf (1 equiv).10 This
© XXXX American Chemical Society
A
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Organic Letters
Letter
Reactions with excess TMSOTf (1.5 equiv) led to an
improved conversion (90%) in 50 min. We then examined
other catalysts in this reaction, and to our surprise we found
that copper(I) (entries 3−6) and a variety of other metals also
expedite this transformation. For example, scandium(III)
triflate and Rh[Cod]2Cl2 with excess TMSOTf (1.5 equiv)
afforded reasonable conversions to vinyl triflate 1a in less than
1 h (entries 7 and 8). However, optimal results were obtained
with Zn(OTf)2 leading to a 91% conversion in 20 min (entry
9).
Bulkier silyl triflate reagents appear to slow the reaction
considerably (entries 10−12). Thus, while TMSOTf leads to
complete conversion in 20 min, reactions of 1 with triethylsilyl
triflate require 210 min to give a similar conversion to vinyl
triflate 1a. With still bulkier silyl triflates, high conversions to 1a
were only achieved after extended reaction times (24−48 h).
Importantly, reactions of 1 performed with catalytic Zn(OTf)2
using KOTf (2.5 equiv) gave no reaction. Similarly, reactions of
1 with stoichiometric amounts of Zn(OTf)2 left only starting
material. Finally, reactions of 1 with 10% Zn(OTf)2 in the
presence of TMSCl (1.5 equiv) afforded only 15−20%
conversion to vinyl triflate 1a even after extended times.
Based on these control studies, it seems that the silyl reagent
serves as more than a soluble source of triflate in the present
reaction.
were rapidly converted to vinyl triflate products especially with
an electron-donating group on the aromatic ring (Table 2,
entry 3). Terminal alkynes bearing alkyl groups (entries 5−9)
required substantially longer times (16−20 h) to produce the
corresponding triflates in good yields.13 Internal alkynes also
reacted slowly and appeared to favor products of Z-geometry
especially with increasing bulkiness of alkyl substituents. We
observed an increase in Z-selectivity from smaller groups such
as methyl (Table 3, entry 1) to isopropyl alkyne 12 which gave
nearly a 5:1 ratio in favor of Z-vinyl triflate 12a (entry 3). An
erosion of the Z-selectivity with extended reaction times (>20
h) was also noted.
In our studies of this reaction, we noticed that the product
yield diminished substantially as greater efforts were made to
rigorously exclude water. When the zinc catalyst was subjected
to high vacuum (0.01 Torr) overnight to remove trace
moisture, the conversion of 1 to 1a decreased to 39% (Table
4, entry 1). The addition of 0.25 equiv of water to this reaction
Table 4. Role of Water in Vinyl Triflate Formation
a
a
We next examined the generality of this method with various
aryl and alkyl alkynes (Tables 2 and 3). Terminal aryl alkynes
entry
H2O (equiv)
R
Z/E
time (h)
conv (%)
1
−
−
H
−
3.0
0.25
3.0
39
36
81
91
79
90
75
91
83
83
87
73
2
Me
H
Table 2. Reactions with Terminal Alkynes
3
0.25
0.25
0.50
0.50
0.75
0.75
1.0
−
1.6
−
0.25
3.0
4
Me
H
5
0.25
3.0
6
Me
H
1.2
7
−
1.1
−
0.25
3.0
8
Me
H
9
0.25
3.0
10
11
12
1.0
Me
H
1.3
1.5
−
1.0
0.25
3.0
1.5
Me
a
1
Determined by H NMR.
led to an 81% conversion. Similar conversions were observed in
the presence of 0.50 and 0.75 equiv of water (entries 5 and 7).
Internal alkyne 10 exhibited similar rate enhancements in the
presence of water (Table 4, R = Me). However, lower
diastereoselectivity was observed as water content was
increased. It appears that the optimal yield and diastereose-
lectivity are achieved with the unmodified commercially
available catalyst.
a
Isolated yields.
Table 3. Reactions with Internal Alkynes
One interpretation for the role of water in this system is that
it hydrolyzes TMSOTf to give triflic acid as the key reactant
produced in a controlled manner throughout the reaction. To
assess this mechanistic possibility, we attempted to mimic the
hypothesized formation of minute quantities of triflic acid
produced under the reaction conditions. This was accomplished
by the slow addition of a dilute solution of triflic acid (0.0010
M in chloroform) to alkyne 10 (Table 5, entry 1). Under these
conditions, vinyl triflate 10a was formed but predominantly as
the E-isomer (Z/E = 0.25). This is a complete reversal of
selectivity relative to our Zn(OTf)2 catalyzed reaction (Table 3,
entry 1). To further evaluate the role of the metal catalyst in
this system, substrate 1 was reacted under identical conditions
a
entry
R
product
silyl
Z/E
time (h) conv (%)
1
2
3
4
5
6
Me (10)
Et (11)
iPr (12)
tBu (13)
Me (10)
Me (10)
10a
11a
12a
13a
10a
10a
Me3Si
Me3Si
Me3Si
Me3Si
Et3Si
2.1
3.0
4.9
−
2.1
2.3
15
14
5
75
81
92
b
−
6
0
75
23
iPr3Si
6
a
b
Isolated yields. Only decomposition observed.
B
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Letter
The method is general to both aliphatic and aromatic terminal
alkynes as well as internal alkynes bearing an aryl substituent.
For Z-diastereoselectivity, the reaction requires silyl triflates
pointing to a unique role for silicon in the mechanism. Further
studies suggest that silicon initially serves as a target for the
nucleophilic vinyl metal intermediate allowing the catalyst to be
regenerated. Subsequent removal of silicon from the substrate
in the presence of limited amounts of water leads to the
observed triflate product. Due to the continuing importance of
vinyl triflates, we believe the present method will find valuable
applications in organic synthesis.
Table 5. Experiments with TfOH in Chloroform
a
a
entry
conditions
R
Z/E
conv (%)
1
2
3
4
5
TfOH (1 equiv, 0.0010 M)
TfOH (1 equiv), Zn(OTf)2
TfOH (1 equiv), Zn(OTf)2
TfOH (1 equiv)
Me
H
0.25
−
1
100
90
b
b
Me
H
100
c
−
1
50
TfOH (1 equiv)
Me
100
a
b
c
1
Determined by H NMR. 0.20 equiv. Starting material completely
ASSOCIATED CONTENT
■
consumed; several side products are observed (see ref 14).
S
* Supporting Information
to those optimized for terminal alkynes (Table 2) except that
TMSOTf was replaced with triflic acid. This reaction resulted in
the formation of vinyl triflate product 1a in 90% conversion
(Table 5, entry 2) which is comparable to the reaction with
TMSOTf (Table 1, entry 9). However, this same reaction in
the absence of Zn(OTf)2 resulted in the formation of product
1a in a much lower conversion (50%) along with several side
products (Table 5, entry 4).14 When the same reactions were
performed using internal alkyne 10, product 10a was rapidly
formed but with no selectivity (entries 3 and 5). These
experiments suggest that both Zn(OTf)2 and an electrophilic
silylating agent are necessary for the (Z)-selectivity observed in
the present reaction.
Experimental procedures and characterization data of all new
1
compounds; copies of H and 13C NMR spectra. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: slepore@fau.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We suggest an alternative role for water in the present
reaction. Instead of producing triflic acid, we expect that water
will react rapidly with TMSOTf to yield a protonated silanol
We thank the National Institutes of Health (GM110651) and
the ACS-PRF (51785) for financial support.
+
(Me3SiOH2 ). Studies suggest that silanols are relatively basic
REFERENCES
■
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step should be slower with hindered silyl triflate agents which is
consistent with our results (Table 1, entries 9−12).
Intermediate B is then protonated to give oxonium ion C
(Scheme 2).17 This species then undergoes desilylation most
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Scheme 2. Proposed Mechanism for Vinyl Triflate
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optimally when the silyl group in C is orthogonal to the
carbonyl unit. This can occur in two conformations; however,
the conformer which minimizes eclipsing interaction between
the R1 and R2 groups is likely preferred (Scheme 2).
Elimination of the silyl in this more favored conformer then
affords the vinyl triflate product with the Z-isomer as the kinetic
product.
In summary, we described a mild reaction for the preparation
of vinyl triflates from alkynes catalyzed by several metal triflates.
C
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(14) The side products are likely due to the formation of vinyl cation
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D
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