Reactivity of a-trifluoromethanesulfonyl esters, amides and ketones: Decarboxylative allylation, methylation, and enol formation

Article abstract of DOI:10.1016/j.jfluchem.2013.03.020

The impact of α-trifluoromethanesulfonyl groups on the chemistry of various carbonyl groups is reported. Allylic α, α-dialkylated- α-trifluoromethanesulfonyl esters readily underwent decarboxylative allylation. α-Trifluoromethylsulfonyl esters, ketones, and amides were all methylated in the presence of trimethylsilyldiazomethane. Esters afforded a mixture of O-and C-methylation; however, ketones and amides offered exclusively O-methylation, with varying degrees of E/Z selectivity, thus affording ambiphilic alkenes. α-Trifluoromethanesulfonyl ketones also exhibited keto-enol tautomerism.

Full text of DOI:10.1016/j.jfluchem.2013.03.020

Journal of Fluorine Chemistry 153 (2013) 151–161
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Reactivity of
a
-trifluoromethanesulfonyl esters, amides and ketones:
Decarboxylative allylation, methylation, and enol formation
1
1
*
Han Il Kong , Monica A. Gill , Amy H. Hrdina, Jennifer E. Crichton, Jeffrey M. Manthorpe
Carleton University, Department of Chemistry, 1125 Colonel By Drive, 203 Steacie Building, Ottawa, ON K1S 5B6, Canada
A R T I C L E I N F O
A B S T R A C T
The impact of
Article history:
a
-trifluoromethanesulfonyl groups on the chemistry of various carbonyl groups is
Received 7 February 2013
Received in revised form 18 March 2013
Accepted 26 March 2013
Available online 6 April 2013
reported. Allylic
a,a-dialkylated-a-trifluoromethanesulfonyl esters readily underwent decarboxylative
allylation. -Trifluoromethylsulfonyl esters, ketones, and amides were all methylated in the presence of
a
trimethylsilyldiazomethane. Esters afforded a mixture of O- and C-methylation; however, ketones and
amides offered exclusively O-methylation, with varying degrees of E/Z selectivity, thus affording
ambiphilic alkenes.
a
-Trifluoromethanesulfonyl ketones also exhibited keto-enol tautomerism.
Keywords:
ß 2013 Elsevier B.V. All rights reserved.
Triflones
Decarboxylative allylation
Keto-enol tautomerism
Diazomethane
Trimethylsilyldiazomethane
Ambiphilic alkenes
O-alkylation of enolates
1. Introduction
more electron deficient trifluoromethyl sulfones and detail how
this work led us to develop a process for preparing ambiphilic
alkenes, including the first sulfonyl-substituted ambiphilic alkenes
derived from amides.
Beginning in the 1970s, the Hendrickson research group
explored the synthesis and reactivity of trifluoromethyl sulfones
(triflones) in alkylation, conjugate addition, and cycloaddition
reactions [1]. Several reagents, both nucleophilic and electrophilic,
have been reported for the construction of thiotrifluoromethyl
groups in various oxidation states [2–8].
2. Results and discussion
Our initial work focused on allyl
a-triflylacetate 2 (Scheme 1),
Metal-catalyzed decarboxylative allylation has proven to be a
highly efficient and popular method for the construction of
carbon–carbon and carbon–heteroatom bonds in both inter- and
intramolecular reactions [9]. One of the key requirements for
metal-catalyzed decarboxylative allylation is an electron with-
drawing group to stabilize the intermediate anion. Given the
exceptional electron withdrawing character of triflones, several
years ago we initiated a research program exploring their viability
in decarboxylative allylation, with an eye toward using them as
alkane synthons via reductive excision of the sulfone group. During
the course of our studies, Tunge and co-workers reported this
process using phenyl sulfones at high temperature [10]. Herein we
wish to report our explorations of this process utilizing the much
which was prepared via reaction of allyl chloroacetate with sodium
iodide and the Langlois reagent, sodium trifluoromethanesulfinate
1 [2]. Palladium-catalyzed decarboxylative allylation was explored
using dipalladium tris(dibenzylideneacetone) and triphenylpho-
sphine. Consumption of the starting material was very rapid at
room temperature but afforded
a mixture of polyallylation
products. This prompted us to prepare an
compound.
a,a-disubstituted
When initial attempts at a seemingly straightforward alkylation
approach did not meet with success (vide infra), we opted for a one-
potorganolithiumapproach. Hendricksonreportedthattheaddition
of organolithiums to N-phenyltriflimide resulted in formation of the
corresponding triflone in good yield. However, other electrophilic
triflyl sources, such as Tf2O afforded bis-triflones [4]. We therefore
examined the reaction of sec-butyllithium with PhNTf2 (Scheme 2).
It is important to note that after the initial (rate-limiting)
nucleophilic attack by the organolithium, a second equivalent of
* Corresponding author. Tel.: +1 613 520 2600x1711; fax: +1 613 520 3749.
E-mail address: jeffrey_manthorpe@carleton.ca (J.M. Manthorpe).
1
These authors contributed equally to this article.
organolithium acts as a base to deprotonate a to the newly formed
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.03.020

152
H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
NaO2SCF3 (1)
20 mol % Pd2(dba)3
80 mol % PPh3
O
O
O
O
NaI
O
O
S
F3C
Cl
S
n
THF, rt
O
F3C
O
CH3CN
80 °C, 2 d
61%
H3-n
2
Scheme 1. Synthesis and decarboxylative allylation of 2.
s–BuLi
O
F3C
O
O
F3C
O
O
F3C
O
N
Ph
O
F3C
O
N
Ph
(2.5 equiv.)
S
H
S
S
S
+
+
PhNTf2
Et2O,
–78 °C - rt
5
5
6
O
Cl
O
R
(0.95 equiv.)
O
O
O
F3C
O
N
O
O
S
S
+
O
R
F3C
O
R
Ph
4
3a R = H 62%
3b R = CH2CH2Ph 40%
Scheme 2. Preparation of allylic
a,a-dialkylated a-triflylaceates.
triflone, affording carbanion 6. We surmised that 6 could be acylated
with an allylic chloroformate to afford our desired starting material.
To our delight, the reaction proceeded as predicted, affording the
desired 3a in 62% yield. However, a critical impurity 4 was also
formed via acylation of the N-phenyltriflamide anion byproduct 5
and separation of these two compounds required judicious
chromatography. Use of other allyl sources, such as allyl cyano-
formate [11] or allyl imidazolyl formate [12] did not improve the
yield or minimize the formation of 4. Use of 0.95 equivalents of
allylic chloroformate proved optimal.
analogous phenyl sulfone system [10], where the same catalyst
system had to be heated to 95 8C to induce allylation and
importantly, a protonated side-product was produced in a 1:1
ratio with the desired product. Here, the protonation side-product
8 was not observed.
A solvent and catalyst loading screen was performed and it was
found that the reaction yield was largely independent of solvent.
Reduction of the catalyst loading to 2 mol% still afforded 7a in good
yield, though lowering the temperature to 0 8C did result in a
noticeable yield attenuation (Table 1).
This one-pot synthesis of 3 has several intriguing features. The
first is that the acylation of anion 6 proceeds at all. Hendrickson
reported extensively studying the acylation of triflone anions and
was only able to provide a single example [13]; however, it is
unclear whether the one-pot approach in Scheme 2 was explored.
We were also surprised that the acylation of 5 and 6 was
competitive, as the drastic difference in their respective pKb values
(ca. 18.8 for 6 [14] vs. ca. 4.35 for 5 [15]) would lead to the
expectation that the 6 would be far more reactive. We surmise that
both of these results are due to a combination of aggregation and
solvent effects, as well as the rate of complexation of 5 and 6 with
the chloroformate electrophile.
We then turned our attention to the preparation of additional
substrates. Variation of the chloroformate proved to be feasible
and afforded 3b in moderate yield. The subsequent decarbox-
ylative allylation proceeded smoothly to afford 7b in 77% yield
(Scheme 4). Again, protonation product 8 was not observed.
The final step in our process was to demonstrate the viability of
our triflones as alkane synthons by reductive cleavage of the
triflone. Magnesium [16], though a convenient reagent, proved
ineffective. However, exposure of 7b to Raney nickel under
hydrogen atmosphere (balloon) offered clean excision of the
sulfone with concomitant alkene hydrogenation (Scheme 5) [17].
We next sought to further broaden the substrate scope by
With test substrate 3a in hand, we attempted palladium-
catalyzed decarboxylative allylation using 5 mol% Pd2(dba)3 and
20 mol% PPh3 (Scheme 3). Gratifyingly, the reaction proceeded
rapidly and in high yield at room temperature to afford desired
homoallylic triflone 7a. This result stands in stark contrast to the
varying the substituents on the a-carbon; however, this proved to
be highly challenging. Preparing secondary alkyllithium reagents
using lithium di-tert-butylbiphenylide [18,19] followed by expo-
sure to PhNTf2 afforded triflones in low yields and presented
purification challenges. Secondary Grignard reagents are not a
Pd2(dba)3 (5 mol%),
PPh3 (20 mol%)
O
O
O
O
O
O
O
H
S
S
S
F3C
F3C
F3C
O
THF, rt, 20 min
92%
8
3a
not
7a
observed
Scheme 3. Palladium-catalyzed decarboxylative allylation of allyl
a,
a-dialkylated
a-triflylacetate 3a.

H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
153
Pd2(dba)3 (2.5 mol%),
O
O
O
O
O
PPh3 (10 mol%)
S
S
F3C
Ph
F3C
O
R
THF, rt, 30 min
77%
3b
7b
R = CH2CH2Ph
Scheme 4. Palladium-catalyzed decarboxylative allylation of allylic
a,
a-dialkylated
a-triflylacetate 3b.
Table 1
H2
Ra Ni
O
O
H
Screening of solvents and catalyst loading
S
Ph
F3C
Ph
EtOH
rt, 8 h
78%
9
7b
Scheme 5. Desulfonylation of 7b with Raney nickel.
Entry
Solvent
Temperature
Mol% Pd
Time
Yield (%)
suitable substitute [20,21]. A sequential alkylation/acylation of
benzyl triflone [1,13,20] was also not fruitful [22].
1
2
3
4
5
6
7
8
9
Et2O
PhMe
PhMe
DCM
DCM
THF
rt
10
10
2
20 min
20 min
17 h
89
86
7
At this point we began considering preparing compounds with
other oxidation states of sulfur (i.e. sulfide and sulfoxide) and
performing subsequent oxidation. Secondary trifluoromethyl
sulfides have been accessed in modest yield via reaction of
disulfides and thiocyanates with trifluoromethyltrimethylsilane
and TBAF [3]. However, in our hands these approaches did not
afford sufficient yield of product when evaluated with dicyclohex-
yldisulfide and cyclohexylthiocyanate.
rt
rt
rt
10
2
20 min
6 h
84
11
92
79
78
61
rt
rt
10
5
20 min
30 min
30 min
30 min
THF
rt
THF
rt
2
THF
0 8C
2
We were hopeful that our desired system could be accessed
in an alternative fashion via the classical Andersen-type
nucleophilic attack on a sulfinate to afford the desired sulfoxide
[23], which could then be oxidized to the sulfone. Moreover, as
this oxidation would erase any chirality at sulfur, we were
content with producing racemic sulfoxide. We prepared
cyclohexyl trifluoromethanesulfinate 10 via in situ conversion
of sodium trifluoromethanesulfinate to trifluoromethanesulfinyl
chloride[1,13] and addition of cyclohexanol. When this com-
pound was exposed to cyclohexylmagnesium bromide, the
desired product 11 was not obtained. Instead, to our surprise,
the CF3 group had been displaced, affording cyclohexyl
cyclohexanesulfinate 12 (Scheme 6). Examination of the litera-
ture offered some hints at this result. For example, Bertrand and
co-workers reported the preparation of 4-phenyl-3-trifluoro-
methanesulfinyloxazolidin-2-one demonstrated that mild
nucleophiles, such as alcohols, amines, and pyrroles could be
triflinated [24]. However, there is no comment on reaction with
harsher nucleophiles, such as Grignard reagents, despite the fact
that the Evans group has reported the utility of oxazolidinone
auxiliaries for the preparation of enantiomerically enriched
sulfoxides [25]. In addition, Prakash, Hu, and Olah have reported
comparison, acetic acid has a pKa of 12.6 in DMSO [29].
Examination of an array of alkylation conditions led only to
recovery of starting material and/or decomposition by nucleo-
philic attack of the halide byproduct on the ester alkyl group. This
in turn leads to decarboxylation and a myriad of other side-
products, as elegantly elucidated by Langlois and co-workers
(Scheme 7) [2a]. Given the highly acidic nature of
a-triflyl esters,
we next considered the viability of diazoalkanes as alkylating
agents. The regioselectivity of such an alkylation was not
immediately clear. Diazoalkanes are certainly ‘‘hard’’ reagents
[30]; however, given the triflyl group’s extraordinary electron
withdrawing character and ability to stabilize negative charge
(which is comparable in strength to that of the nitro group [28],
though the two groups operate via different mechanisms), it is not
unambiguous whether the hard site in
a-triflyl esters is the
enolate oxygen or carbon. This results in six potential reaction
products, arising from mono- or bis-C-methylation, E- or Z-
selective O-methylation, and C-methylation followed by O-
methylation.
In order to evaluate the viability of this hypothesis, we prepared
cyclohexyl triflylacetate 13 from the corresponding bromide and 1
[1]. Exposure of 13 to trimethylsilyldiazomethane (10 equiv.) in
MeOH at room temperature for 1 h resulted in a mixture of three
major methylation products: a 1.5:1 ratio of C-methylation (14) to
O-methylation (15) (Scheme 8). Alkene 15 was isolated as a 1.8:1
mixture of olefin isomers. The bis-C,O- and bis-C,C-methylation
products were not observed.
ꢀ
the displacement of CF3 from PhSO2CF3 upon exposure to
potassium tert-butoxide in DMF [26].
At this stage we elected to revisit the alkylation of allylic
triflylacetates [27]. Alkylation of this class of compounds is
actually non-trivial. Triflylacetate esters are exceptionally acidic
C–H acids: ethyl triflylacetate has a pKa of 6.4 in DMSO [28]; by
CyOH
O
S
O
S
O
S
1
Py
CyMgCl
O
S
SO2Cl
F3C
O
ref. 11
DCM,
rt, 1 h
PhMe
0 °C - rt,
1h
F3C
Cl
F3C
O
10
11
not
observed
12
40%
70%
Scheme 6. Sulfinate approach to trifluoromethylsulfoxides.

154
H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
O
O
O
O
O
O
O
O
X–
S
R2
multiple
products
S
S
F3C
F3C
O
R1
F3C
O
R2 R2
R2 R2
R2
RCH2X
CO2
Scheme 7. Decarboxylation of
a-triflyl acetates.
Me3SiCHN2
O
O
OCH3
O
F3C
O
O
F3C
O
O
F3C
O
(10 equiv.)
S
Cy
S
Cy
S
Cy
+
O
O
O
0.5 M, MeOH
rt, 1 h
CH3
12 / 15
1.5 : 1
13
Scheme 8. Methylation of ester 13 with trimethylsilyldiazomethane.
O
OCH3
Y
sterically
OCH3
O
O
F3CO2S
F3CO2S
F3CO2S
favored
F3CO2S
F3CO2S
+
OEt
F3CO2S
18
for large Y
Y
Y
OEt
CH3
17
O
Y
Me3SiCHN2
OCH3
OEt
OCH3
O
O
O
O
O
(10 equiv.)
CH3
O
Me3SiCHN2
ROH
+
F3CO2S
S
S
OEt
+
F3C
OEt
F3C
Y
O
0.5 M, MeOH
rt, 1 h
CH3
SO2CF3
promoted
by strength
of Tf as EWG
Y = alkyl, aryl, NR2
F3CO2S
16
19
20
Y
H3C CH3
OCH3
OEt
SO2CF3
21
Scheme 9. Methylation of ester 16 with TMS-diazomethane.
H3C
17 / 18 / 19 / 20 / 21
8 : 4 : 4 : 1 : 1
sterically
OCH3
O
Y
favored
for small Y,
electronically
favored
Y
SO2CF3
SO2CF3
Scheme 10. Rationale for regio- and stereoselectivity in methylation of
a-triflyl
carbonyls.
Under the same conditions, ethyl triflylacetate 16 afforded an
8:4:4:1:1 mixture of products arising from C-methylation (17),
non-selective O-methylation (18 and 19), and non-selective bis-
C,O-methylation (20 and 21, Scheme 9). This served to further
substantiate the ambiguity of the hard site in the conjugate base of
triflylacetyl esters. While these product distributions were not
ideal, we did achieve the necessary level of reactivity and surmised
that if the reactivity could be tuned in either direction the products
would be interesting. C-alkylation would achieve our initial goal
related to our allylation chemistry and O-alkylation would afford
ambiphilic alkenes with clearly defined nucleophilic and electro-
philic termini.
Several a-triflyl amides were prepared from two equivalents of
the corresponding amine and bromoacetyl bromide or 2-bromo-
propionyl bromide, followed by SN2 reaction with sodium
trifluoromethanesulfinate in DMA (Table 2). The preparation of
a
-triflyl esters and ketones has been reported previously [2a];
however, to the best of our knowledge this is the first work [27] on
the synthesis of
a-triflyl tertiary acetamides.
Table 2
The amount of charge borne by the enolate oxygen varies with
the nature of the substituent adjacent to the carbonyl; therefore
we postulated that carbonyl compounds other than esters would
be more regioselective in their reaction with trimethylsilyldiazo-
Synthesis of
a-triflyl amides
methane. Consequently, we elected to probe the methylation of a-
triflyl ketones and amides (Scheme 10) with the anticipation that
these should afford predominantly O-methylation due to increased
electron density on the enolate oxygen. E/Z stereochemistry of the
products was anticipated to reflect the kinetic enolate geometry
ratios, as reactions of the enolate counterion, methyldiazonium,
have been shown to be quite rapid [31]. We also expected olefin
geometry to be a function of both steric effects, which would
favour the Z-enolate if the alkoxide is smaller than the Y group (NR2
in amides or alkyl/aryl group in ketones), and electronic effects,
which would favour the E-alkene via a minimization of dipoles. It
was expected that the amides would fall under steric control, as
minimization of A1,3-strain leads virtually all acyclic monosub-
stituted amide enolates to favour the Z configuration [32]. Ketones
were predicted to be more substrate-dependent, with larger Y
groups promoting Z olefin formation.
Entry
R1, R2
R3
Equiv. 1
Step 2 temp.
Product
Yield
(8C), time
(%, 2 steps)
1
2
3
4
5
(CH2)4
(CH2)2O
i–Pr2
H
H
H
H
H
1.5
60, 2 d
70, 3 d
70, 3 d
70, 3 d
70, 4 d
22
23
24
25
26
90
52
54
86
72
2.0
1.5
Et2
1.5
n-Bu, H
1.2 + 0.5
after 2 d
1.5 + 0.85
after 4 d
6
(CH2)4
CH3
70, 7 d
27
41

H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
155
O
O
1, NaI
Cl
SO2CF3
DMA
50 °C, 3 d
43%
29
28
O
O
1
Br
SO2CF3
31
DMA
50 °C, 24 h
79%
Ph
Ph
30
1. Me3SiCHN2
2. HBr
1
O
O
O
Br
SO2CF3
33
Cy
Cl
O
Cy
Cy
DMA
70 °C, 24 h
32
40% (3 steps)
NBS(0.3 equiv.)
p-TSA (cat.)
O
O
1
Br
SO2CF3
35
Et2O, rt, 3 h
DMA
70 °C, 3 d
>99%
34
(2 steps)
NBS,
O
O
O
p-TSA (cat.)
1
Br
SO2CF3
Ph
Ph
Ph
neat,
80 °C,
10 min
DMA
50 °C, 3 d
35%
Ph
Ph
Ph
37
36
(2 steps)
Scheme 11. Synthesis of
a-triflyl ketones.
We also synthesized
a
selection of
a
-triflyl ketones
(Scheme 11). The requisite
commercially available, while
a
a
-halo ketones 28 and 30 were
-bromination of the correspond-
ing ketone afforded 34 and 36 [33]. Since cyclohexyl methyl
ketone is not commercially available, bromomethyl ketone 32
was accessed via reaction of cyclohexanecarbonyl chloride
with trimethylsilyldiazomethane, followed by treatment with
HBr [34].
Upon examination of their 1H NMR spectra, we discovered
that several of the ketones exhibited significant enol content, a
Table 3
Keto/enol ratios of several
a
-triflyl ketones in different deuterated solvents.a
Ketone
CDCl3
65:35
DMSO-d6
Acetone-d6
13:87
91:9
phenomenon previously observed anecdotally in
a-perfluoro-
sulfonyl ketones [35]. We elected to carry out a survey of this
phenomenon by varying the solvent and structure of the ketone
and observed several general trends (Table 3). Conjugated
ketones exhibit less enol tautomer than non-conjugated ketones.
In CDCl3 and DMSO-d6 the cyclic ketone 29 displayed a higher
enol content than the acyclic examples. In all cases but two (31
and 37 in DMSO-d6), the keto/enol tautomerization was slower
than the NMR timescale, thus affording distinct peaks for the
keto and enol tautomers. Perhaps the most intriguing results
arise from 35, which offered no detectable enol content in CDCl3,
while affording 92% enol content in acetone-d6. We surmise that
this latter result is due to the ability of acetone to act as a
hydrogen bond acceptor for the enol or 35 and acetone’s planar
character provides a less sterically crowded environment than
the trigonal pyramidal DMSO. Moreover, the acyclic nature of 35
could allow it to adopt conformations more favorable to
stabilization of the enol form, including the E configuration of
the enol. This is in contrast to the cyclic 29. We presume sterics
also play a role, as the ethyl group of 29 is less bulky than the
phenyl and cyclohexyl groups of 31 and 33, respectively.
94:6
91:9
100:0
65:35
74:26
8:92
Broad peaks
100:0
85:15
94:6
Broad peaks
80:20
All samples were 1 mM in the noted solvent and all spectra (1H, 13C and 19F
a
With an assortment of
a-triflyl ketones and amides in hand, we
NMR) were acquired at ambient temperature.
selected amide 22 as our model. Reaction with 10 equiv. of

156
H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
Me3SiCHN2
(2.5 equiv.)
O
OCH3
SO2CF3
0.5 M: 50% conversion
1 M: 100% conversion
SO2CF3
33
Cy
Cy
EtOH
rt, 12 h
39
Scheme 12. Optimization of methylation of
a-triflyl ketone 33.
Table 4
trimethylsilyldiazomethane from 10 to 2.5. Further experimenta-
tion showed that EtOH could be effectively used with THF, Et2O, or
EtOAc in a 1:1 ratio. Notably, changing the reaction concentration
from 0.5 M to 1.0 M (with respect to the sulfone) was inconse-
quential for amide 22; however, to achieve full conversion of
ketone 33 the higher concentration was obligatory (Scheme 12).
With our optimized reaction conditions in hand, we began to
evaluate other substrates (Table 5). The nature of the nitrogen
Optimization of methylation of
a-triflyl amide 22.
Entry
Me3SiCHN2
(equiv.)
Solvent
Conc.
(M)
Time
(h)
Conv.
(%)a
substituents impacted the methylation of
a-triflyl amides. While
the reaction conditions had been optimized for the methylation of
pyrrolidinyl amide 22, more sterically hindered amides 24 and 25
1
2
10
10
10
5
MeOH
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
3
3
100
100
68
EtOH
were not as effectively methylated (entries
3 and 4) and
3
i–PrOH
MeOH
3
4
24
24
24
12
12
12
12
12
12
12
100
100
86
methylation of the secondary amide 26 proceeded in low yield
(entry 5). As expected, only the Z-alkene was observed for all
tertiary amide substrates; intriguingly, secondary amide 26, which
lacks the A1,3-strain of the tertiary amides, also afforded the Z-
5
5
EtOH
6
5
i–PrOH
MeOH
7
2.5
2.5
2.5
1.5
2.5
2.5
2.5
50
8
EtOH
100
100
47
9
EtOH
alkene exclusively (entry 5). Not unexpectedly,
a-methyl amide 27
was completely unreactive, with the increased A1,3-interactions
10
11
12
13
EtOH
1
EtOH/THF
EtOH/Et2O
EtOH/EtOAc
1
90
likely causing a lack of overlap of the C–H bond and the carbonyl
orbital [37].
p*
1
94
1
91
Analogous to
effective O-methylation for all substrates examined. In the cyclic
(29) and -methylene substrates (31 and 33), the Z olefin was
obtained exclusively (entries 7–9). Contrary to our results with
substituted amides, -substituted ketones 35 and 37 were reactive
but afforded E/Z mixtures (entries 10–11).
Though trimethylsilyldiazomethane has significant advantages
over diazomethane, we nevertheless opted to explore the utility of
diazomethane for this transformation. Ethereal diazomethane
a-triflyl amides, a-triflyl ketones demonstrated
a
Determined by integration of the 1H NMR spectrum of the crude reaction
mixture.
a
a
-
trimethylsilyldiazomethane at 0.5 M in MeOH for 3 h resulted in
100% conversion (Table 4). Gratifyingly, the Z-alkene 38 was the
only observed product; no C-methylation or bis-methylation
products were found. We then set out to optimize the reaction
conditions. In order to ensure complete desilylation, we initially
limited our solvents to simple alcohols. Though methanol is
commonly used in conjunction with trimethylsilyldiazomethane
[36], ethanol proved to be the superior solvent for the formation of
38, as it enabled the reduction of the number of equivalents of
a
successfully reacted with
a-triflyl ketone 31 (Scheme 13),
achieving full conversion after 24 h.
We also sought to investigate the kinetics of the methylation.
Given that ketones are more acidic than the corresponding amides
CH2N2
(2 equiv.)
O
OCH3
SO2CF3
SO2CF3
Et2O,
rt, 24 h
31
46
100% conversion
Scheme 13. Methylation of 31 by diazomethane.
O
O
SO2CF3
SO2CF3
SO2CF3
SO2CF3
+
+
N
Me3SiCHN2
O
O
(1 equiv.)
22
31
SO2CF3
SO2CF3
+
N
EtOH
OCH3
OCH3
rt, 12 h
22
31
N
38
46
22 / 31 / 38 / 46
50 : 25 : 0 : 25
Scheme 14. Competitive methylation of
a-triflyl ketone 31 and a-triflyl amide 22.

H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
157
Table 5
Methylation of
a-triflyl amides and ketones
Entry
1
S.M.
Product
Conv. (%)a
100
Yield (%)
74
Z/E Ratiob
22
100:0
2
3
23
24
100
80
22
100:0
29 (12 h) 63 (48 h)
100:0
4
25
65 (12 h) 100 (18 h)
44
100:0
100:0
5
6
26
27
25 (12 h) 45 (60 h)
16 (12 h) 23 (60 h)
0c 0d
7
8
29
31
100
100
66 89e
100:0
100:0
92
9
33
35
100
100
68
77
100:0
25:75
10

158
H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
Table 5 (Continued )
Entry
11
S.M.
Product
Conv. (%)a
82
Yield (%)
48
Z/E Ratiob
37
n.d.
a
Determined by integration of the 1H NMR spectrum of the crude reaction mixture.
Assigned via 2D NOESY experiment.
b
c
Under standard conditions.
d
e
5 equiv. Me3SiCHN2, 1 M in EtOH, rt, 5 days.
10 equiv. Me3SiCHN2, 1 M in EtOH, rt, 3 h.
˚
and, conversely, amides enolate are more reactive than their
ketone analogues, we opted to perform a competition experiment
to determine whether the rate-limiting step of the reaction is
diazoalkane protonation or enolate methylation. When equimolar
amounts of ketone 31 and amide 22 were combined with 1
equivalent of trimethylsilyldiazomethane we observed 46 as the
sole methylation product; amide methylation product 38 was not
obtained (Scheme 14). Accordingly, we concluded that the
protonation of diazomethane is likely the rate-limiting step in
the reaction mechanism; however, given the apparent termole-
cular pathway of carboxylic acid esterification with trimethylsi-
lyldiazomethane [38], we cannot rule out more complex
behaviour. It is also notable that these conditions offered only
50% conversion of 31, consistent with our previous observation
that excess trimethylsilyldiazomethane is required to effect
complete reaction.
by TLC using glass-backed Extra Hard Layer (60 A) TLC plates from
Silicycle and visualized by fluorescence quenching under UV light
and/or staining using potassium permanganate. Flash chro-
matographic purification of products was performed either on
Silia-P Flash silica gel from Silicycle using a forced flow of eluent by
the method of Still [18] or by automated chromatography on a
Biotage Isolera One equipped with a UV detector. Concentration in
vacuo refers to rotary evaporation at 40 8C at the appropriate
pressure. Yields refer to purified and spectroscopically pure
compounds unless explicitly indicated as crude. NMR spectra
were recorded on a Bruker Avance III 300 or Bruker AMX 400 MHz
spectrometer. Chemical shifts are reported in ppm. Tetramethyl-
silane was used as the internal standard for 1H and 13C NMR
spectra. 19F NMR spectra are referenced to trifluorotoluene
(ꢀ63.7 ppm). IR spectra were recorded on a Varian 1000 Scimitar
Series or an ABB Bomem MB Series spectrometer. Absorptions are
given in wavenumbers (cmꢀ1). High-resolution electron impact
mass spectrometry (HR-EI-MS) was performed on
a Kratos
3. Conclusion
Concept-11A mass spectrometer with an electron beam of 70 eV
at the Ottawa-Carleton Mass Spectrometry Center. High-resolution
electrospray mass spectrometry (HR-ESI-MS) was conducted using
an ABI SciEx QSTAR XL electrospray quadrupole time-of-flight
spectrometer with cesium iodide as an internal reference.
Compounds 22–27 [27], 29 [27], and 31–48 [27] were prepared
as previously reported.
In conclusion, we have demonstrated the rapid Pd(0)-catalyzed
decarboxylation of allylic
challenges in substrate preparation. However, these challenges
led us to utilize the exceptional acidity of -triflyl carbonyl
compounds to explore their methylation with trimethylsilyldia-
zomethane. We have also prepared an array of -triflyl amides and
a-triflyl esters, despite significant
a
a
ketones and the latter exhibit varying degrees of keto/enol
tautomerism. We have also demonstrated a facile method for
4.2. Experimental procedures
the stereoselective synthesis of
a-triflyl enol ethers and a-triflyl
4.2.1. Allyl trifluoromethanesulfonylacetate (2)
ketene aminals, both of which can be classified as ambiphilic
alkenes. We are currently exploring the chemistry of these
compounds as electrophiles and substrates for cycloadditions,
including cyclopropanation to afford a new class of donor-acceptor
cyclopropanes (Scheme 15) [39] and results will be reported in due
course.
A mixture of sodium trifluoromethanesulfinate (1, 672 mg, 4.3
mmol, 1.0 equiv.), allyl chloroacetate (0.50 mL, 4.3 mmol,
1.0 equiv.), and sodium iodide (155 mg, 6.5 mmol, 1.5 equiv.)
were sequentially added to MeCN (5 mL) and the solution was
heated to reflux for 40 h. After cooling to room temperature water
(10 mL) was added and the mixture was washed with EtOAc
(3 ꢁ 5 mL). The combined organic layers were dried over magne-
sium sulfate, filtered, and concentrated in vacuo. The residue was
purified by column chromatography (7% EtOAc/hexanes) to afford
2 as a colourless oil (589 mg, 59%).
4. Experimental
4.1. General methods
Rf = 0.16 (10% EtOAc/hexanes); 1H NMR (CDCl3, 400 MHz):
5.94 (m, 1H), 5.31–5.45 (m, 2H), 4.77 (d, J = 5.9 Hz, 2H), 4.28 (s,
d
All reagents were purchased from commercial sources and were
used as received, without further purification. Methylene chloride
was distilled from CaH2 prior to use. THF was distilled from lithium
aluminum hydride prior to use. Crude products were analyzed
2H); 13C NMR (CDCl3, 75 MHz):
d 159.2, 130.2, 120.3, 119.1 (q,
J = 327 Hz), 67.9, 54.6; 19F NMR (377 MHz):
d
ꢀ77.8; IR (thin film):
H3C
Nu
Y
CH3O
"CH2"
CH3O
Nu–
O
O
CF3
O
O
O
CF3
O
O
CF3
S
S
S
Y
Y
donor-acceptor
cyclopropane
Scheme 15. Potential applications of ambiphilic alkenes.

H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
159
3093, 3000, 2946, 1750, 1651, 1379, 1283, 1211, 1120; HR-ESI-MS:
solution. PPh3 (6.6 mg, 0.025 mmol, 10 mol%) was added to
the reaction mixture, and then left to stir for 30 min. The solution
progressively changed from the original deep red colour to a
clear dark green. A solution of ester 3a (68.0 mg, 0.25 mmol,
m/z calcd for C6H6F3O4S (MꢀH+) 230.9944; found: 230.9945.
4.2.2. Allyl 2-methyl-2-(trifluoromethanesulfonyl)butanoate (3a)
sec-Butyllithium (1.4 M in cyclohexane, 1.0 mL, 1.4 mmol,
2.5 equiv.) was added dropwise to solution of N-phenyl-bis(tri-
fluoromethanesulfonimide) (200 mg, 0.56 mmol, 1.0 equiv.) in
THF (2.8 mL, 0.2 M) at –78 8C in a Schlenk flask. The reaction
mixture was allowed to warm over 1 h and was then re-cooled to
ꢀ78 8C. Allyl chloroformate (0.056 mL, 0.53 mmol, 0.95 equiv.)
was added dropwise and the reaction mixture was stirred for 8 h
without further addition of dry ice to the cooling bath. The reaction
was quenched with saturated aqueous ammonium sulfate.
Mixture was extracted with 2ꢁ 10 mL diethyl ether, and the
combined organic extracts were washed with brine and then dried
over magnesium sulfate. Filtration, followed by concentration
1.0 equiv.) in THF (200
mL) was then added to the Pd mixture
dropwise over a 2-min period. The reaction was monitored by
TLC and was complete in less than 30 min. The solvent was
removed in vacuo, then the crude mixture was purified via flash
chromatography (2.5% EtOAc/hexane) to give a colorless oil
(53 mg, 92%).
Rf = 0.47 (10% ethyl acetate/hexanes); 1H NMR (CDCl3,
400 MHz):
d 5.80 (ddt, J = 16.8, 10.0, 7.6 Hz, 1 H), 5.22 (dd,
J = 16.8, 1.6 Hz, 1H), 5.24–5.26 (m, 1H), 2.76 (dd, J = 14.4, 7.2 Hz,
1H), 2.57 (dd, J = 14.0, 7.2 Hz, 1H), 2.03 (dq, J = 14.8, 6.8 Hz, 1H),
1.88 (dq, J = 14.8, 7.2 Hz, 1H), 1.48 (d, J = 1.2 Hz, 3H), 1.09 (t,
J = 7.6 Hz, 3H). 13C NMR (CDCl3, 75 MHz):
d
129.5, 120.9, 120.7 (q,
yielded
a pale yellow oil, which was purified by column
J = 332 Hz), 56.2, 37.4, 26.7, 19.2, 8.2. 19F NMR (CDCl3, 376.5 MHz):
chromatography on silica gel (2% EtOAc/hexanes) to afford 3a
(94 mg, 62% yield) as a colourless oil.
d
ꢀ71.1. IR (thin film): 1622, 1594, 1439, 1419, 1341, 1204, 1121,
948, 887. HR-EI-MS: (M+) not observed; m/z calcd for C7H13
(M+ꢀSO2CF3): 97.1012; found: 97.1039.
Rf = 0.40 (10% ethyl acetate/hexanes); 1H NMR (CDCl3,
400 MHz):
d 5.92 (ddt, J = 17.1, 10.3, 6.0 Hz, 1H), 5.42 (ddt,
J = 17.1, 1.4, 1.3 Hz, 1H), 5.32 (m, 1H), 4.73 (m, 1H), 2.50 (m, 1H),
2.04 (m, 1H), 1.74 (s, 3H), 1.01 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3,
4.2.6. (E)-(6-Methyl-6-((trifluoromethyl)sulfonyl)oct-3-en-1-
yl)benzene (7b)
100 MHz):
d
165.5, 130.4, 122.6 (q, J = 330 Hz), 120.1, 74.7, 67.6,
Prepared in analogy to 7a as a colorless oil (77%). The E/Z ratio
(determined by integration of 19F NMR spectrum) of 7b was 88:12.
25.9, 16.0, 8.3; 19F NMR (CDCl3, 376.5 MHz):
d
ꢀ70.9; IR (thin film):
3092, 2987, 2952, 2918, 2890, 2849, 1745, 1462, 1363, 1316, 1203,
1156, 1128, 1097, 1052; HR-EI-MS: (M+) not observed; m/z calcd
for C6H8F3O3S (M+ꢀOC3H5): 217.0135; found: 217.0121.
Rf = 0.56 (10% EtOAc/hexanes); 1H NMR (CDCl3, 400 MHz):
d
7.15–7.30 (m, 5H), 5.57–5.71 (m, 1H, mixture of cis/trans isomers),
5.32–5.43 (m, 1H, mixture of cis/trans isomers), 2.71 (t, J = 7.2 Hz,
2H), 2.60–2.67 (m, 1H, mixture of cis/trans isomers), 2.44–2.52 (m,
1H, mixture of cis/trans isomers), 2.39 (td, J = 7.2, 7.2 Hz, 2H), 1.81–
1.98 (m, 1H, mixture of cis/trans isomers), 1.69–1.79 (m, 1H,
mixture of cis/trans isomers), 1.40 (d, J = 0.8 Hz, minor isomer),
1.35 (d, J = 1.2 Hz, 3H), 1.03 (t, J = 7.2 Hz, minor isomer, over-
lapping with peak for major isomer at 1.02 ppm), 1.02 (t, J = 7.6 Hz,
4.2.3. (E)-5-Phenylpent-2-en-1-yl chloroformate
Diphosgene (265
mL, 2.2 mmol, 0.6 equiv.) was added dropwise
to a solution of E-5-phenylpent-2-en-1-ol [40] (600 mg, 3.7 mmol,
1.0 equiv.) in diethyl ether (3.7 mL, 1.0 M relative to allylic
alcohol). Following 5 min of stirring, N,N-dimethylaniline
(470
m
L, 3.7 mmol, 1.0 equiv.) was added dropwise. After 20 min
3H); 13C NMR (CDCl3, 100 MHz):
d 141.4, 136.1, 134.1, 128.5
the reaction mixture was allowed to warm to room temperature.
After 8 h, argon was bubbled through the reaction mixture to
remove any remaining phosgene. The mixture was then diluted
with diethyl ether and filtered through a medium porosity fritted
funnel. The filtrate was concentrated in vacuo to give desired
product (quantitative yield). The product was used without any
further purification.
d 7.30–7.33 (m, 2 H), 7.18–7.24 (m,
3H), 5.92–6.01 (m, 1H), 5.61–5.70 (m, 1H), 4.60 (d, J = 6.8 Hz, 2H),
2.75 (t, J = 7.2 Hz, 2H), 2.44 (dt, J = 7.6, 7.2 Hz, 2H).
(minor isomer), 128.5, 128.4 (minor isomer), 128.3, 126.0 (minor
isomer), 125.9, 122.4, 122.3 (minor isomer), 120.2 (q, J = 246 Hz),
70.1 (minor isomer), 69.9, 36.1, 35.5 (minor isomer), 35.4, 34.1,
30.4 (minor isomer), 29.4, 26.8 (minor isomer), 26.6, 19.0, 18.9
(minor isomer), 8.4 (minor isomer), 8.3.; 19F NMR (CDCl3,
376.5 MHz):
d
ꢀ71.1 (minor isomer), ꢀ71.2 (major isomer). IR
(thin film): 3028, 2985, 2945, 2857, 1604, 1497, 1456, 1349, 1199,
1138, 1123, 1103, 1030, 974. HR-EI-MS: m/z calcd for C16H21F3O2S:
334.1214; Found: 334.1218.
1H NMR (400 MHz, CDCl3):
4.2.7. 6-Methyl-1-phenyloctane (9)
4.2.4. (E)-5-Phenylpent-2-en-1-yl 2-methyl-2-
((trifluoromethyl)sulfonyl)butanoate (3b)
Raney1 2800 nickel, slurry in water, was washed five times
with distilled water until the pH of the supernatant was neutral,
then the Raney Ni was slurried in anhydrous ethanol. (6-methyl-6-
(trifluoromethanesulfonyl)oct-3-en-1-yl)benzene (51.7 mg, 0.15
mmol, 1 equiv.) was dissolved in anhydrous ethanol in a Schlenk
flask, then the washed slurry of Raney Ni was transferred to the
flask. The flask headspace was briefly evacuated under vacuum,
then backfilled with a balloon of hydrogen gas. This was repeated
three times. The reaction flask was left under H2 pressure at room
temperature for 8 h while monitoring by TLC. The mixture was
filtered through Celite, then concentrated in vacuo to yield a light
yellow oil. Flash chromatography (100% hexane) gave 9 as a
colorless oil (24 mg, 78%).
Prepared in analogy to 3a to afford 3b as a colourless oil (40%).
Rf = 0.47 (10% ethyl acetate/hexanes); 1H NMR (CDCl3,
400 MHz):
d 7.26–7.31 (m, 2H), 7.16–7.21 (m, 3H), 5.88 (m, 1H),
5.60 (m, 1H), 4.64 (m, 2H), 4.59 (d, minor isomer), 2.71 (t, J = 7.2 Hz,
2H), 2.47 (m, unresolved due to overlap with q at 2.40), 2.40 (q,
J = 7.6 Hz, 2H), 2.02 (dq, J = 15.2, 6.8 Hz, 1H), 1.72 (s, 3H), 0.98 (t,
J = 7.2 Hz, 3H). 13C NMR (CDCl3, 100 MHz) (major isomer):
d
165.5,
141.3, 137.3, 128.4, 126.0, 124.0, 122.9, 120.4 (q, J = 330 Hz), 74.7,
67.7, 35.2, 33.9, 25.9, 16.0, 8.3. 19F NMR (CDCl3, 376.5 MHz):
d
ꢀ70.9. IR (thin film): 3029, 2944, 2858, 1742, 1673, 1604, 1497,
1456, 1362, 1316, 1202, 1155, 1127, 1096, 1052, 1030. HR-EI-MS:
(M+) not observed; m/z calcd for C5H8F3O2S+ [M+ꢀC(O)OC11H13]:
189.0175; Found: 189.0192; m/z calcd for C11H13+: 145.1012;
Found: 145.1026.
Rf = 0.72 (hexane); 1H NMR (400 MHz, CDCl3)
d 7.25–7.29 (m,
2H), 7.15–7.19 (m, 3H), 2.60 (t, J = 8.0 Hz, 2H), 1.58–1.65 (m, 2H),
1.24–1.37 (m, 7H), 1.07–1.17 (m, 2H), 0.83–0.87 (m, 6H). 13C NMR
(100 MHz, CDCl3)
d 143.0, 128.4, 128.2, 125.5, 36.5, 36.0, 34.4, 31.6,
4.2.5. 4-Methyl-4-((trifluoromethyl)sulfonyl)hex-1-ene (7a)
29.7, 29.5, 27.0, 19.2, 11.4. IR (thin film): 3027, 2960, 2928, 2856,
Pd2(dba)3 (5.8 mg, 6.3
(2.5 mL) under argon with constant stirring to produce a deep red
m
mol, 2.5 mol%) was dissolved in THF
1605, 1496, 1463, 1377, 1030. HR-EI-MS: m/z calcd for C15H24
204.1878; Found: 204.1869.
:

160
H.I. Kong et al. / Journal of Fluorine Chemistry 153 (2013) 151–161
(b) J.B. Hendrickson, K.W. Bair, R. Bergeron, A. Giga, P.L. Skipper, D.D. Sternbach,
J.A. Wareing, Org. Prep. Proced. Int. 9 (1977) 173–207.
4.2.8. Cyclohexyl trifluoromethanesulfinate (10)
A solution of mesitylenesulfonyl chloride (3.32 g, 15.2 mmol,
1.0 equiv.) and sodium trifluoromethanesulfinate (1, 2.50 g,
16.0 mmol, 1.05 equiv.) in acetonitrile (20 mL) was stirred at room
temperature for 1 h, then cooled in an ice bath. A solution of
cyclohexanol (1.61 mL, 15.2 mmol, 1.0 equiv.) and pyridine
(1.23 mL, 15.2 mmol, 1.0 equiv.) in acetonitrile (7.0 mL, 2.2 M)
was prepared and added dropwise over 5 min to the cooled solution
prepared previously. The reaction mixture was allowed to warm
slowly to room temperature over 18 h. The milky reaction mixture
was then diluted with diethyl ether (100 mL) and washed with
water (5ꢁ 50 mL). The organic phase was washed with 3ꢁ 50 mL
brine, then dried over magnesium sulfate, filtered and concentrated
in vacuo to produce a yellow oil (2.30 g, 70%) that was sufficiently
pure to proceed to the next step. An analytical sample was purified
by flash chromatography (10% EtOAc/hexanes).
[2] (a) F. Eugene, B. Langlois, E. Laurent, J. Fluorine Chem. 66 (1994) 301–309;
(b) M. Tordeux, B. Langlois, C. Wakselman, J. Org. Chem. 54 (1989) 2452–2453.
[3] (a) T. Billard, B.R. Langlois, Tetrahedron Lett. 37 (1996) 6865–6868;
(b) T. Billard, S. Large, B.R. Langlois, Tetrahedron Lett. 38 (1997) 65–68.
[4] J.B. Hendrickson, K.W. Bair, J. Org. Chem. 42 (1977) 3875–3878.
[5] J.B. Hendrickson, D.A. Judelson, T. Chancellor, Synthesis (1984) 320–322.
[6] (a) P. Eisenberger, I. Kieltsch, R. Koller, K. Stanek, A. Togni, Org. Synth. 88 (2011)
168–180;
(b) I. Kieltsch, P. Eisenberger, A. Togni, Angew. Chem. Int. Ed. 46 (2007) 754–757;
(c) S. Capone, I. Kieltsch, O. Flo¨gel, G. Lelais, A. Togni, D. Seebach, Helv. Chim. Acta
91 (2008) 2035–2056.
[7] C. Chen, Y. Xie, L. Chu, R.-W. Wang, X. Zhang, F.-L. Qing, Angew. Chem. Int. Ed. 51
(2012) 2492.
[8] G. Teverovskiy, D.S. Surry, S.L. Buchwald, Angew. Chem. Int. Ed. 50 (2011) 7312.
[9] (a) For recent reviews on metal-catalyzed decarboxylative allylation, see: J.D.
Weaver, A. Recio III, A.J. Grenning, J.A. Tunge, Chem. Rev. 111 (2011) 1846–1913;
(b) J.F. Hartwig, L.M. Stanley, Acc. Chem. Res. 43 (2010) 1461–1475.
[10] (a) J.D. Weaver, J.A. Tunge, Org. Lett. 10 (2008) 4657–4660;
(b) J.D. Weaver, B.J. Ka, D.K. Morris, W. Thompson, J.A. Tunge, J. Am. Chem. Soc.
132 (2010) 12179–12181.
Rf = 0.64 (10% ethyl acetate/hexanes); 1H NMR (CDCl3,
[11] M. Childs, W. Webber, J. Org. Chem. 41 (1976) 3486.
[12] B.M. Trost, J. Xu, J. Org. Chem. 72 (2007) 9372.
400 MHz):
13C NMR (CDCl3, 75 MHz):
24.8, 23.5, 23.4; 19F NMR (276 MHz):
2864, 1732, 1453, 1373, 1200, 1132, 1033, 1004; HR-EI-MS: m/z
calcd for C6H11O2S (M+ꢀCF3) 147.0474; found: 147.0498; m/z calcd
for CF3OS: 116.9622; found: 116.9594; m/z calcd for C6H11
(M+ꢀSO2CF3): 83.0855; found: 83.0877.
d
4.54 (septet, J = 4.0 Hz, 1H), 1.19–2.02 (m, 10H);
122.7 (q, J = 334 Hz), 82.0, 33.1, 33.0,
ꢀ81.1; IR (thin film): 2942,
d
[13] J.B. Hendrickson, P.L. Skipper, Tetrahedron 32 (1976) 1627–1635.
[14] F.G. Bordwell, N.R. Vanier, W.S. Matthews, J.B. Hendrickson, P.L. Skipper, J. Am.
Chem. Soc. 97 (1975) 7160–7162.
[15] SciFinder Scholar. Calculated using Advanced Chemistry Development (ACD/
Labs) Software V11.02.
[16] See also Ref. [8]. Magnesium is typically limited to reduction of aromatic sulfones.
See: A.C. Brown, L.A. Carpino, J. Org. Chem. 50 (1985) 1749–1750.
[17] Careful TLC monitoring of the reaction demonstrated that sulfone cleavage and
alkene reduction proceeded at competitive rates.
d
[18] Lithium 4,40-di-tert-butylbiphenylide. e-Encyclopedia of Reagents for Organic
Synthesis [Online]; Wiley, Posted 15.4.01. http://onlinelibrary.wiley.com/o/eros/
articles/rl088/frame.html (accessed 15.10.12).
[19] Few secondary alkyllithiums are commercially available and their preparation is
considerably more tedious than their Grignard brethren. We explored the gener-
ation of the requisite alkyllithiums from the corresponding halides using lithium
di-tert-butylbiphenylide but product yields were quite low and contrary to our
initial expectations, our triflones were actually quite non-polar and co-eluted
with the di-tert-butylbiphenyl byproduct.
4.2.9. Cyclohexyl cyclohexanesulfinate (12)
Cyclohexyl trifluoromethanesulfinate (10, 505 mg, 2.3 mmol,
1.0 equiv.) was dissolved in toluene (12.5 mL, 0.2 M) and the
solution was cooled in an ice bath. Cyclohexylmagnesium chloride
(2.9 mL, 2.0 M in diethyl ether, 5.8 mmol, 2.5 equiv.) was added
dropwise over 5 min. Cooling bath was maintained for 15 min, then
reaction mixture was allowed to warm to room temperature over
45 min. Reaction was quenched with saturated aqueous ammonium
chloride and extracted with 3ꢁ 25 mL methylene chloride. The
combinedorganicextractswerewashedwithbrine(3ꢁ 25 mL), then
dried over sodium sulfate, filtered and concentrated in vacuo. The
crude product was purified via flash chromatography (10% EtOAc/
hexane) to yield 12 (213 mg, 40%) as a colourless oil.
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bromine and iodine, respectively. Primary organomagnesium chlorides were
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opted to revisit the acylation of triflone anions. Despite testing a thorough array of
reaction conditions, we, like Hendrickson et al. (see Ref. [1,13]), were unable to
achieve the desired outcome.
Rf = 0.24 (10% ethyl acetate/hexanes); 1H NMR (CDCl3,
400 MHz):
1H), 1.68–2.01 (m, 10H), 1.21 – 1.61 (m, 12H). 13C NMR (100 MHz,
CDCl3) 78.8, 63.8, 33.8, 32.9, 25.7, 25.2, 25.2, 25.1, 24.5, 23.8, 23.7
d 4.81 (tt, J = 9.6, 4.0 Hz, 1H), 2.52 (tt, J = 11.2, 4.0 Hz,
d
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Acknowledgements
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J.M.M. thanks NSERC (Discovery and RTI programs), Canada
Foundation for Innovation (Leaders Opportunity Fund), Ontario
Research Fund, and Carleton University for financial support.
M.A.G. acknowledges the Government of Ontario for an Ontario
Graduate Scholarship. M.A.G. and H.I.K. thank Carleton University
for financial support. The authors also wish to thank Prof. Jeff Smith
and Karl Wasslen for performing high-resolution electrospray
mass spectrometry experiments.
Appendix A. Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.jfluchem.2013.
03.020.
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tautomerism, see Y. Kobayashi, T. Yoshida, I. Kumadaki, Tetrahedron Lett. 20
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