Study of the Reactivity of [Hydroxy(tosyloxy)iodo]benzene Toward Enol Esters to Access α-Tosyloxy Ketones

Article abstract of DOI:10.1021/acs.joc.5b00948

The reactivity of enol esters toward [hydroxy(tosyloxy)iodo]benzene (HTIB) was assessed. These substrates were found to be rapidly converted in high yields to their corresponding α-tosyloxy ketones. This transformation demonstrates that these substrates can act as ketone surrogates. The scope of the method was investigated and aromatic, aliphatic, and cyclic enol esters were found to be suitable substrates for the reaction. The relative reactivity of a model substrate toward HTIB and m-CPBA was investigated, and it was found that the reaction could be performed under catalytic conditions.

Full text of DOI:10.1021/acs.joc.5b00948

Note
pubs.acs.org/joc
Study of the Reactivity of [Hydroxy(tosyloxy)iodo]benzene Toward
Enol Esters to Access α‑Tosyloxy Ketones
Benoit Basdevant and Claude Y. Legault*
́ ́ ́
Universite of Sherbrooke, CCVC, Department of Chemistry, 2500 Boul. de l’Universite, Sherbrooke, Quebec J1K 2R1, Canada
S
* Supporting Information
ABSTRACT: The reactivity of enol esters toward [hydroxy(tosyloxy)iodo]-
benzene (HTIB) was assessed. These substrates were found to be rapidly
converted in high yields to their corresponding α-tosyloxy ketones. This
transformation demonstrates that these substrates can act as ketone
surrogates. The scope of the method was investigated and aromatic, aliphatic,
and cyclic enol esters were found to be suitable substrates for the reaction.
The relative reactivity of a model substrate toward HTIB and m-CPBA was
investigated, and it was found that the reaction could be performed under
catalytic conditions.
ypervalent iodine compounds have proven to be
H
proficient reagents in synthetic chemistry and have
been an alternative to toxic transition metals in numerous
oxidation reactions.1 For this reason, hypervalent iodine
chemistry has received increasing attention over the past
three decades. Important advances are periodically made in
either the development of new hypervalent iodine reagents or
the application of known reagents to new transformations.
Another area of active research is the development of catalytic2
and enantioselective systems for a broad range of applications
in organic chemistry.3 Our group has studied the functionaliza-
tion of ketones,4 in particular, the α-tosyloxylation reaction,
which was initially reported by Koser et al. using [hydroxy-
(tosyloxy)iodo]benzene (HTIB)5 (eq 1).6
Unfortunately, such derivatives are too reactive to be used in
the conditions of the currently developed catalytic method-
ologies. Surprisingly, the investigation of enol analogues toward
HTIB is scarce. We envisioned, in the hope of achieving access
to catalytic systems, exploiting enol analogues bearing electron-
withdrawing groups on the oxygen atom, such as enol esters.
These substrates, having lower nucleophilicity, could possibly
be used under catalytic conditions without degradation.
Moreover, enol esters can be obtained through numerous
other methodologies, such as the addition of carboxylic acids to
alkynes.11 This would effectively increase the available paths to
access α-substituted ketones from nonketonic substrates.
Herein, we evaluate the reactivity of various enol ester
derivatives toward HTIB. We reveal that enol esters can be
cleanly converted to their corresponding α-tosyloxy ketone
products. Additionally, we demonstrate that they can serve as
substrates in iodine(III)-mediated catalytic systems.
The selected enol analogue candidates were easily obtained
from the corresponding ketone under basic conditions. The
evaluation of substrate reactivity is presented in Table 1 using
enol analogues derived from propiophenone as a reference.
The substrates were allowed to react with a slight excess of
HTIB at room temperature. Reaction completion was
monitored by the disappearance of the HTIB suspension, as
its solubility in the reaction conditions is very low. It is
important to note that under these conditions HTIB is almost
unreactive toward propiophenone (<5% conversion in 12 h).
Simple methyl enol ether 1a led to major degradation under the
Pioneering work by Wirth et al. has demonstrated that the
process could be rendered catalytic and enantioselective.7
Despite the work of numerous groups7,8 and as well as our
own,9 the enantioselectivities attained for this transformation
have remained low (<60% ee). Access to these enantiopure
products would be of great interest as they are polyvalent chiral
percursors that could serve as building blocks in synthesis. In an
attempt to surpass this current limitation, we have initiated the
study of substrates that would effectively lead to the same α-
tosyloxy ketone products. Enol analogues would be convenient
substrates to access such products using Koser’s methodology.
Moriarty et al. have, for example, demonstrated the rapid
conversion of silyl enol ethers to their corresponding α-tosyloxy
ketones using HTIB (eq 2).10
Received: April 28, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00948
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
suspension and conversion of 1b was almost instantaneous (∼1
min), but the reaction conditions led to numerous side
products, resulting in only 43% yield of 2 (Table 2, entry 7).
Whereas the addition of an acid catalyst does lead to rate
enhancement, for the sake of simplicity and atom economy, the
scope of the reaction was evaluated using only HTIB at 40 °C
(Table 2, conditions from entry 2). The results are presented in
Table 3.
Table 1. Evaluation of Enol Analogues 1a−d Reactivity
Toward HTIB
a
entry
R
time (h)
yield (%)
1
2
3
4
Me (1a)
4
7
<5
92
91
90
MeCO (1b)
t-BuCO (1c)
p-TolSO2 (1d)
Table 3. Study of the Reaction Scope of the Conversion of
Acetyl Enol Esters to α-Tosyloxy Ketones
13
48
a
Isolated yields after flash chromatography. Values reported are the
average of a minimum of two experiments.
described conditions. Gratifyingly, acetyl enol ester 1b was
converted cleanly to desired product 2 in excellent yields
(Table 1, entry 2). The pivaloyl enol ester 1c showed slightly
lower reactivity with complete conversion in 13 h (Table 1,
entry 3). The steric hindrance of the acyl group thus has a
noticeable effect on reactivity. We also tested the p-
toluenesulfonyl enol ester 1d to evaluate the effect of a
stronger electron-withdrawing group on the enol oxygen.
Whereas 1d was found to be much less reactive than enol esters
1b or 1c, it was converted cleanly to 2 in 48 h. Acetyl enol ester
1b was selected as the ideal substrate for further optimization
due the size and cost of its acyl group. The effect of
temperature and additives on the reaction of 1b with HTIB
was next investigated. The results are illustrated in Table 2.
Table 2. Evaluation of Reaction Conditions on the
Conversion of 1b to 2
a
entry T (°C)
additive
X (equiv) time (min) yield (%)
1
2
3
4
5
6
7
25
40
25
25
40
25
25
420
50
10
60
13
180
1
92
94
92
91
95
89
43
TsOH·H2O
TsOH·H2O
TsOH·H2O
AcOH
1.0
0.1
0.1
0.1
1.0
BF3·OEt2
a
Isolated yields after flash chromatography. Results reported are the
average of a minimum of two experiments.
A slight elevation in temperature (+15 °C) increases the
reaction rate significantly, enabling complete conversion of 1b
within 50 min without any loss in yield (Table 2, entry 2). The
effect of acid additives was investigated next. The addition of a
stoichiometric quantity of TsOH·H2O led to a drastic increase
in the reaction rate, affording 2 in 92% yield within 10 min
(Table 2, entry 3). Even a catalytic quantity of TsOH·H2O (0.1
equiv) increased the reaction rate drastically (Table 2, entry 4).
Using the same catalytic quantity of TsOH·H2O and increasing
the temperature to 40 °C enabled complete conversion of 1b
within 13 min, affording 2 in 95% yield (Table 2, entry 5). The
addition of AcOH also resulted in a noticeable, albeit smaller,
rate enhancement (Table 2, entry 6). Finally, we evaluated the
use of trifluoroborane etherate, a commonly used Lewis acid in
iodine(III)-mediated processes.12 Disappearance of the HTIB
a
Isolated yield after flash chromatography. Results reported are the
b
average of a minimum of two experiments. Substrate 3g is a mixture
of both Z and E isomers. Reaction performed in dichloromethane
instead of acetonitrile. 1,4-Naphthoquinone is obtained as the major
side product.
c
d
B
DOI: 10.1021/acs.joc.5b00948
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The Journal of Organic Chemistry
Note
We first studied substrates bearing both an aromatic group
and an aliphatic chain. The length of the alkyl chain on the enol
ester did not significantly influence the rate of the reaction
(Table 3, entries 1−3). In contrast, modulation of the
electronic properties of the aromatic moiety has a drastic effect
on the substrate reactivity toward HTIB. The presence of an
electron-rich aromatic moiety resulted in a roughly 3-fold rate
acceleration (Table 3, entries 5 and 6). The effect of electron-
withdrawing groups was more noticeable. For example,
introduction of a trifluoromethyl (CF3) group at the meta
position of the aromatic group caused a decrease in reactivity
by a factor of more than 10 (Table 3, entry 7). Moving the CF3
group to the ortho position thus caused deactivation for both
electronic and steric reasons, resulting in an almost 100-fold
decrease in reactivity (Table 3, entry 8). The reaction of
substrate 3h, bearing two phenyl groups, led to a modest yield
(34%) of desired product 4h (Table 3, entry 9). The lower
yield with this specific substrate can be attributed to a side
reaction with acetonitrile, as 4,5-diphenyl-2-methyloxazole
(28%) was also isolated under these conditions. Product 4h
was obtained in a very good yield (84%) by performing the
reaction in dichloromethane to prevent this side reaction
(Table 3, entry 10). Substrate 3i, derived from tetralone, also
resulted in a modest yield of the desired compound (Table 3,
entry 10). It was found by analysis of the 1H NMR spectrum of
the crude mixture that product 4i is not stable under the
reaction conditions. It undergoes rapid elimination of TsOH,
followed by aromatization to yield 1-naphthol. The latter is
then further oxidized by HTIB to produce 1,4-naphthoquinone.
To favor formation of the latter, substrate 3i was reacted with
an excess of HTIB (2 equiv). Under these conditions, 1,4-
naphthoquinone was isolated in very good yield (86%). Finally,
we investigated the reactivity of enol esters bearing two
aliphatic groups. Reaction of enol ester 3j, derived from
cyclohexanone, with HTIB afforded desired compound 4j in
74% yield (Table 3, entry 12). The lower yield in comparison
to other substrates is attributed to partial elimination of TsOH
and formation of cyclohexenone, as found by analysis of the 1H
NMR spectrum of the crude mixture. Attempts to change the
reaction conditions did not lead to an increase in the isolated
yield of 4j. The reaction of 3k, an acyclic substrate bearing two
aliphatic groups, led to the formation of 4k in excellent yield
(Table 3, entry 13). The slight decrease in reactivity is
attributable to steric hindrance of the t-butyl group.
The potential of acetyl enol esters to be used as substrates in
catalytic systems was investigated last. Classical catalytic
conditions involve in situ generation of HTIB from PhI and
an excess of TsOH·H2O and m-chloroperbenzoic acid (m-
CPBA). We evaluated the stability and relative reactivity of enol
ester 1b toward these reagents to determine if selective reaction
with HTIB was possible under catalytic conditions. The
conversion rates of 1b are illustrated in Figure 1.
This substrate was found to be stable in the presence of
TsOH·H2O, showing no noticeable degradation (e.g., hydrol-
ysis) over a period of 6 h. Without the presence of TsOH·H2O,
compound 1b showed a similar kinetic profile toward both m-
CPBA and HTIB. However, in the presence of TsOH·H2O,
more representative of the actual catalytic conditions, a great
increase in reactivity with HTIB was observed, whereas
reactivity with m-CPBA remained mostly unaffected. These
kinetic profiles supported the feasibility of selective reaction
with HTIB in the presence of an excess of m-CPBA and TsOH·
H2O. As expected, the α-tosyloxy ketone product 2 was
Figure 1. Kinetic profiles of 1b with TsOH, m-CPBA, and HTIB.
obtained in 74% yield under catalytic conditions by slow
addition of 1b to a mixture of 20 mol % of phenyl iodide and a
stoichiometric quantity of m-CPBA and TsOH·H2O in
acetonitrile at room temperature (eq 3).
In summary, we have demonstrated that enol esters are
proficient substrates to access α-tosyloxy ketones by reaction
with HTIB. Despite the presence of an electron-withdrawing
group on the enol oxygen, they react rapidly under mild
conditions, similarly to silyl enol ethers.10 In contrast to the
latter, they are more stable in acidic and oxidative conditions.
This has permitted us to develop catalytic conditions for this
transformation. Additionally, the acyl enol esters are accessible
through numerous methodologies even from nonketonic
precursors.11 The described transformation can thus serve to
devise novel synthetic strategies to access α-substituted ketone
intermediates.
EXPERIMENTAL SECTION
■
General Remarks. All nonaqueous reactions involving air or
moisture-sensitive compounds were run under an inert atmosphere
(nitrogen or argon) with rigid exclusion of moisture from reagents and
glassware using standard techniques.13 All glassware was stored in the
oven and/or was flame-dried prior to use under an inert atmosphere of
gas. Anhydrous solvents were obtained either by distillation over
sodium (THF, ether, toluene) or over calcium hydride (CH2Cl2,
Et3N). Analytical thin-layer chromatography (TLC) was performed on
precoated, glass-backed silica gels (Merck 60 F254). Visualization of the
developed chromatogram was performed by UV absorbance, aqueous
cerium molybdate, ethanolic phosphomolybdic acid, iodine, or
aqueous potassium permanganate. Flash column chromatography
was performed using 230−400 mesh silica (EM Science or Silicycle) of
the indicated solvent system according to standard techniques.14
Melting points were obtained on a Buchi melting point apparatus and
are uncorrected. Infrared spectra were taken on an FTIR instrument
and are reported in reciprocal centimeters (cm−1). Nuclear magnetic
resonance spectra (1H, 13C, DEPT, COSY, HMQC) were recorded on
1
either a 300 or 400 MHz spectrometer. Chemical shifts for H NMR
spectra are recorded in parts per million (ppm) from tetramethylsilane
with the solvent resonance as the internal standard (chloroform, δ 7.27
ppm, acetonitrile, δ 1.94 ppm). Data are reported as follows: chemical
shift multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qn =
quintet, sext = sextuplet, m = multiplet and br = broad) and the
C
DOI: 10.1021/acs.joc.5b00948
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The Journal of Organic Chemistry
Note
coupling constant is in Hz for integration. Chemical shifts for 13C
NMR spectra are recorded in ppm from tetramethylsilane using the
central peak of deuterochloroform (77.23 ppm) as the internal
standard. All spectra were obtained with complete proton decoupling.
When ambiguous, proton and carbon assignments were established
using COSY, NOESY, HMQC, and DEPT experiments. High
resolution mass spectra were performed using an UPLC-Q-TOF
(ESI) mass spectrometer.
1e as a white solid; Tfus 64−68 °C; Rf = 0.43 (EtOAc:hexanes, 10:90);
1H NMR (300 MHz, CDCl3) δ 7.70 (d, J = 8.3 Hz, 2H), 7.36−7.11
(m, 8H), 5.82 (q, J = 7.0 Hz, 1H), 2.42 (s, 3H), 1.75 (d, J = 7.0 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 147.4, 144.8, 141.2, 134.9, 134.0,
129.4, 128.1 125.5, 117.3, 107.0, 21.6, 12.2; IR (neat) 3061, 2924,
1597, 1370, 1177, 1093, 984, 827, 727 cm−1; HRMS ESI (m/z) calcd
for C16H16NaO3S [MNa]+ 311.0712, found 311.0711.
(Z)-1-Phenylbut-1-en-1-yl Acetate (3a). The title compound was
(1-Methoxyprop-1-en-1-yl)benzene (1a). Propiophenone (4.47
mmol) was mixed with trimethylorthoformate (4.92 mmol) and p-
toluenesulfonic acid (0.022 mmol). The mixture was stirred for 24 h,
and then the MeOH formed was distilled. The product was purified by
distillation under reduced pressure (20 Torr, 80 °C) to provide 144
obtained as a colorless oil (78% yield) according to the general vinyl
acetate formation procedure; Rf = 0.48 (10% EtOAc/hexanes); H
1
NMR (300 MHz, CDCl3) δ 7.47−7.28 (m, 5H), 5.84 (t, J = 7.4 Hz,
1H), 2.32 (s, 3H), 2.17 (qn J = 7.5 Hz, 2H), 1.09 (t, J = 7.5 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 168.8, 145.6, 128.5, 128.0, 124.3, 119.8,
64.5, 20.6, 19.7, 13.5; IR (neat) 2967, 2935, 1759, 1666, 1494, 1370
1209, 1034, 749 cm−1; HRMS ESI (m/z) calcd for C12H14NaO2
[MNa]+ 213.0886, found 213.0889.
1
mg (36% yield) (1.7:1 Z:E) of 1a as a colorless oil; H NMR (300
MHz, CDCl3) δ 7.53−7.26 (m, 5H), 5.44 (q, J = 6.9 Hz, 1H, Z), 4.86
(q, J = 7.0 Hz, 1H, E), 3.68 (s, 3H, E), 3.60 (s, 3H, Z), 1.86 (d, J = 6.9
Hz, 3H, Z), 1.75 (d, J = 7.0 Hz, 3H, E); 13C NMR (75 MHz, CDCl3) δ
155.5, 155.3, 136.2, 136.0, 128.7, 128.3, 127.9, 127.90, 127.6, 125.7,
108.9, 94.1, 58.4, 55.0, 12.8, 11.0; IR (neat) 2935, 2832, 1656, 1445,
1224, 1073, 771, 698 cm−1; HRMS ESI (m/z) calcd for C10H12NaO
[MNa]+ 171.0780, found 171.0790.
(Z)-1-Phenyloct-1-en-1-yl Acetate (3b). The title compound was
obtained as a colorless oil (78% yield) according to the general vinyl
1
acetate formation procedure; Rf = 0.73 (10% EtOAc/hexanes); H
NMR (300 MHz, CDCl3) δ 7.46−7.20 (m, 1H), 5.85 (t, J = 7.4 Hz,
1H), 2.32 (s, 1H), 2.15 (q, J = 7.2 Hz, 1H), 1.54−1.19 (m, 2H), 0.93
(t, J = 6.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 168.7, 146.0, 135.1,
128.5, 128.0, 124.3, 118.4, 38.6, 31.7, 29.1, 26.3, 22.6, 20.7, 14.1; IR
(neat) 2928, 2856, 1761, 1369, 1205, 1183, 1021, 757, 692 cm−1;
HRMS ESI (m/z) calcd for C16H22NaO2 [MNa]+ 269.1512, found
269.1519.
(Z)-1-Phenylprop-1-en-1-yl Acetate (1b).15 General Vinyl Acetate
Formation Procedure. n-Butyllithium (9.6 mmol) was added to a
solution of diisopropylamine (9.6 mmol) in THF (40 mL) in a flame-
dried round-bottom flask under an argon atmosphere at −78 °C. The
mixture was stirred for 30 min, and then propiophenone (8 mmol)
was added. The resulting mixture was stirred for 45 min, and then
acetic anhydride (16 mmol) was added. The reaction was stirred 30
min at −78 °C and another 30 min at room temperature. The mixture
was poured into saturated NaHCO3 (100 mL), and extracted thrice
with EtOAc (60 mL). The combined organic layers were washed with
brine and dried over MgSO4, and the solvent was removed under
reduced atmosphere. The crude mixture was purified by column
chromatography on silica gel with EtOAc:hexanes (5:95 to 20:80) to
(Z)-1-(p-Tolyl)prop-1-en-1-yl Acetate (3c). The title compound
was obtained as a colorless oil (84% yield) according to the general
vinyl acetate formation procedure; Rf = 0.39 (10% EtOAc/hexanes);
1H NMR (400 MHz, CDCl3) δ 7.35−7.24 (m, 3H), 7.13 (d, J = 7.9
Hz, 2H), 5.84 (dd, J = 13.9, 7.0 Hz, 1H), 2.33 (s, 3H), 2.30 (s, 3H),
1.70 (d, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 168.6, 147.0,
137.9, 132.3, 129.2, 124.2, 111.6, 21.1, 20.6, 11.5; IR (neat) 2920,
1760, 1670, 1513, 1369, 1207, 1184, 1030, 798 cm−1; HRMS ESI (m/
z) calcd for C12H14NaO2 [MNa]+ 213.0886, found 213.0886.
(Z)-1-(4-Methoxyphenyl)prop-1-en-1-yl Acetate (3d). The title
compound was obtained as a colorless oil (88% yield) according to the
general vinyl acetate formation procedure; Rf = 0.41 (10% EtOAc/
1
provide 1.35 g (96% yield) of 1b as a colorless oil; H NMR (300
MHz, CDCl3) δ 7.51−7.41 (m, 2H), 7.41−7.24 (m, 3H), 5.93 (q, J =
6.9 Hz, 1H), 2.27 (s, 3H), 1.74 (d, J = 6.9 Hz, 3H); HRMS ESI (m/z)
calcd for C11H12NaO2 [MNa]+ 199.0730, found 199.0729.
1
(Z)-1-Phenylprop-1-en-1-yl Pivalate (1c). n-Butyllithium (3.9
mmol) was added to a solution of diisopropylamine (3.9 mmol) in
THF (17 mL) in a flame-dried round-bottom flask under an argon
atmosphere at −78 °C. The mixture was stirred for 30 min, and then
propiophenone (3.25 mmol) was added. The resulting mixture was
stirred for 45 min, and pivaloyl chloride (6.5 mmol) was added. The
reaction was stirred 30 min at −78 °C and another 30 min at room
temperature. The mixture was poured into saturated NaHCO3 (50
mL) and extracted thrice with EtOAc (60 mL). The combined organic
layers were washed with brine and dried over MgSO4, and the solvent
was removed under reduced atmosphere. The crude mixture was
purified by column chromatography on silica gel with EtOAc:hexanes
(5:95 to 20:80) to provide 647 mg (91% yield) of 1c as a colorless oil;
hexanes); H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.8 Hz, 2H),
6.83 (d, J = 8.9 Hz, 2H), 5.75 (q, J = 7.0 Hz, 1H), 3.78 (d, J = 1.2 Hz,
3H), 2.28 (d, J = 1.2 Hz, 3H), 1.67 (d, J = 7.0 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ 168.7, 159.5, 146.7, 127.8, 125.7, 113.9, 110.7, 55.3,
20.7, 11.5; IR (neat) 3029, 2919, 1760, 1512, 1368, 1207, 1184, 1030,
798 cm−1; HRMS ESI (m/z) calcd for C12H14NaO3 [MNa]+ 229.0835,
found 229.0846.
(Z)-1-(Thiophen-2-yl)prop-1-en-1-yl Acetate (3e). The title com-
pound was obtained as a pale yellow oil (96% yield) according to the
general vinyl acetate formation procedure; Rf = 0.52 (10% EtOAc/
1
hexanes); H NMR (300 MHz, CDCl3) δ 7.18 (dd, J = 4.9, 1.3 Hz,
1H), 7.03−6.92 (m, 2H), 5.83 (q, J = 7.1 Hz, 1H), 2.32 (s, 3H), 1.70
(d, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 168.3, 142.1,
139.1, 127.3, 124.5, 123.0, 112.4, 20.5, 11.4; IR (neat) 2938, 1764,
1667, 1435, 1370, 1201, 1025, 851, 805, 702 cm−1; HRMS ESI (m/z)
calcd for C9H10NaO2S [MNa]+ 205.0294, found 205.0294.
1
Rf = 0.52 (EtOAc:hexanes, 10:80); H NMR (400 MHz, CDCl3) δ
7.43−7.23 (m, 5H), 5.89 (q, J = 7.0 Hz, 1H), 1.71 (d, J = 7.0 Hz, 3H),
1.41 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 175.9, 147.0, 135.5,
128.4, 127.9, 124.3, 112.4, 39.2, 27.3, 11.3; IR (neat) 2975, 2872, 1750,
1494, 1479, 1264, 1126, 1112, 1031, 753, 692 cm−1; HRMS ESI (m/z)
calcd for C14H18NaO2 [MNa]+ 241.1199, found 241.1199.
(Z)-1-(3-(Trifluoromethyl)phenyl)prop-1-en-1-yl Acetate (3f). The
title compound was obtained as a pale yellow oil (96% yield)
according to the general vinyl acetate formation procedure; Rf = 0.42
1
(Z)-1-Phenylprop-1-en-1-yl 4-Methylbenzenesulfonate (1d). n-
Butyllithium (3.9 mmol) was added to a solution of diisopropylamine
(3.9 mmol) in THF (17 mL) in a flame-dried round-bottom flask
under an argon atmosphere at −78 °C. The mixture was stirred for 30
min, and then propiophenone (3.25 mmol) was added. The resulting
mixture was stirred for 45 min, and p-toluenesulfonic anhydride (6.5
mmol) was added. The reaction was stirred 30 min at −78 °C and
another 30 min at room temperature. The mixture was poured into
saturated NaHCO3 (50 mL), extracted thrice with EtOAc (60 mL).
The combined organic layers were washed with brine and dried over
MgSO4, and the solvent was removed under reduced atmosphere. The
crude mixture was purified by column chromatography on silica gel
with EtOAc:hexanes (5:95 to 20:80) to provide 824 mg (82% yield) of
(10% EtOAc/hexanes); H NMR (300 MHz, CDCl3) δ 7.69−7.39
(m, 4H), 6.00 (q, J = 7.0 Hz, 1H), 2.34 (s, 3H), 1.76 (d, J = 7.0 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 145.8 (s), 136.0 (s), 131.0 (q, J =
32.3 Hz), 129.4 (s), 129.0 (s), 127.5 (s), 124.6 (q, J = 3.7 Hz), 124.0
(q, J = 272.4 Hz), 121.1 (q, J = 3.9 Hz), 114.6 (s), 20.5 (s), 11.6 (s);
IR (neat) 2985, 1764, 1444, 1335, 1203, 1127, 797 cm−1; HRMS ESI
(m/z) calcd for C12H11F3NaO2 [MNa]+ 267.0603, found 267.0602.
1-(2-(Trifluoromethyl)phenyl)prop-1-en-1-yl Acetate (3g). The
title compound was obtained as a pale yellow oil (92% yield) (1:3
Z:E) according to the general vinyl acetate formation procedure; Rf =
1
0.44 (10% EtOAc/hexanes); H NMR (300 MHz, CDCl3) δ 7.79−
7.39 (m, 4H), 5.69 (q, J = 7.2 Hz, 1H Z), 5.51 (q, J = 6.9 Hz, 1H E),
2.17 (s, 3H E), 2.09 (s, 3H Z), 1.76 (d, J = 6.9 Hz, 3H Z), 1.57 (d, J =
D
DOI: 10.1021/acs.joc.5b00948
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
7.2 Hz, 3H E); 13C NMR (75 MHz, CDCl3) δ 169.7 (s), 168.8 (s),
145.5 (s), 144.2 (s), 135.1 (q, J = 2.1 Hz), 133.5 (s), 132.0 (s), 131.7
(s), 131.5 (s), 128.9 (s), 128.5 (s), 127.8 (q, J = 30.9 Hz), 126.2 (q, J =
5.5 Hz), 123.9 (q, J = 273.5 Hz), 117.3 (s), 117.0 (s), 21.0 (s), 20.7
(s), 12.6 (s), 11.5 (s); IR (neat) 2984, 1759, 1375, 1315, 1211, 1169,
1131, 768 cm−1; HRMS ESI (m/z) calcd for C12H11F3NaO2 [MNa]+
267.0603, found 267.0613
(m, 6H), 0.83 (t, J = 6.9 Hz, 3H); HRMS ESI (m/z) calcd for
C21H26NaO4S [MNa]+ 397.1444, found 397.1444.
1-Oxo-1-p-tolylpropan-2-yl 4-Methylbenzenesulfonate (4c).9b
The title compound was obtained as a light brown solid (95% yield)
1
according to the general α-tosyloxy ketone formation procedure; H
NMR (400 MHz, CDCl3) δ 7.84−7.66 (m, 4H), 7.34−7.18 (m, 4H),
5.82−5.69 (m, 1H), 2.40 (s, 3H), 2.39 (d, J = 5.9 Hz, 3H), 1.57 (dd, J
= 6.9, 3.3 Hz, 3H); HRMS ESI (m/z) calcd for C17H18NaO4S [MNa]+
341.0818, found 341.0810.
(Z)-1,2-Diphenylvinyl Acetate (3h).16 The title compound was
obtained as a pale yellow oil (90% yield) according to the general vinyl
acetate formation procedure; 1H NMR (300 MHz, CDCl3) δ 7.56 (dd,
J = 11.4, 4.6 Hz, 1H), 7.47−7.24 (m, 2H), 6.73 (s, 1H), 2.34 (s, 3H).
HRMS ESI (m/z) calcd for C16H14NaO2 [MNa]+ 261.0886, found
261.0885.
1-(4-Methoxyphenyl)-1-oxopropan-2-yl 4-Methylbenzenesulfo-
nate (4d). The title compound was obtained as a light brown solid
(93% yield) according to the general α-tosyloxy ketone formation
1
procedure; Rf = 0.08 (10% EtOAc/hexanes); H NMR (400 MHz,
3,4-Dihydronaphthalen-1-yl Acetate (3i).17 The title compound
was obtained as a pale yellow oil (98% yield) according to the general
CDCl3) δ 7.94−7.82 (m, 2H), 7.75 (d, J = 8.3 Hz, 2H), 7.31−7.21 (m,
2H), 6.97−6.84 (m, 2H), 5.73 (q, J = 6.9 Hz, 1H), 3.87 (s, 3H), 2.40
(s, 3H), 1.57 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
193.0, 164.1, 145.0, 133.5, 131.2, 129.7, 127.9, 126.4, 114.0, 77.5, 77.3,
77.1, 76.6, 55.5, 21.6, 18.8; IR (neat) 1689, 1359, 1175, 845, 758, 666
cm−1; HRMS ESI (m/z) calcd for C17H18NaO5S [MNa]+ 357.0767,
found 357.0774.
1
vinyl acetate formation procedure; H NMR (300 MHz, CDCl3) δ
7.24−7.06 (m, 1H), 5.73 (t, J = 4.7 Hz, 1H), 2.90 (t, J = 8.1 Hz, 1H),
2.48 (td, J = 8.1, 4.7 Hz, 1H), 2.33 (s, 1H); HRMS ESI (m/z) calcd for
C12H12NaO2 [MNa]+ 211.0730, found 211.0743.
Cyclohex-1-en-1-yl Acetate (3j). Cyclohexanone (6.3 mmol) was
mixed with acetic anhydride (12.6 mmol) and p-toluenesulfonic acid
(0.6 mmol). The mixture was refluxed for 24 h, then cooled to room
temperature, poured into saturated aqueous NaHCO3 solution (150
mL), and extracted thrice with diethyl ether (75 mL). The combined
organic layers were washed with brine and dried over MgSO4, and the
solvent was removed under reduced atmosphere. The product was
purified by distillation under reduced pressure (20 Torr, 80 °C) to
provide 3.7 g (70% yield) of 3j as a colorless oil; 1H NMR (300 MHz,
CDCl3) δ 5.38 (s, 1H), 2.14 (s, 7H), 1.79−1.69 (m, 2H), 1.61 (dd, J =
11.7, 6.2 Hz, 2H); HRMS ESI (m/z) calcd for C8H12NaO2 [MNa]+
163.0730, found 163.0737.
(Z)-2,2-Dimethyl-6-phenylhex-3-en-3-yl Acetate (3k). The title
compound was obtained as a pale yellow oil (72% yield) according to
the general vinyl acetate formation procedure; Rf = 0.83 (10% EtOAc/
hexanes); 1H NMR (300 MHz, CDCl3) δ 7.38−7.08 (m, 5H), 5.16 (t,
J = 7.0 Hz, 1H), 2.84−2.59 (m, 1H), 2.19 (s, 3H), 2.18−2.11 (m, 2H),
1.08 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 168.4, 155.1, 141.9,
128.4, 128.3, 125.8, 112.5, 36.0, 35.2, 28.0, 26.4, 20.6; IR (neat) 2969,
1758, 1454, 1369, 1208, 1098, 1048, 699 cm−1; HRMS ESI (m/z)
calcd for C16H22NaO2 [MNa]+ 269.1512, found 269.1518.
1-(3-(Trifluoromethyl)phenyl)-1-oxopropan-2-yl 4-Methylbenze-
nesulfonate (4e).9b The title compound was obtained as a colorless
oil (93% yield) according to the general α-tosyloxy ketone formation
1
procedure; H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.5 Hz, 2H),
7.83 (d, J = 7.8 Hz, 1H), 7.71 (d, J = 8.3 Hz 2H), 7.60 (t, J = 7.7 Hz,
1H), 7.29−7.21 (m, 2H), 5.70 (q, J = 7.0 Hz, 1H), 2.40 (s, 3H), 1.61
(d, J = 7.0 Hz, 3H); HRMS ESI (m/z) calcd for C17H15F3NaO4S
[MNa]+ 395.0535, found 395.0532.
1-Oxo-1-(2-(trifluoromethyl)phenyl)propan-2-yl 4-Methylbenze-
nesulfonate (4f).9b The title compound was obtained as a colorless
oil (82% yield) according to the general α-tosyloxy ketone formation
procedure; NMR (300 MHz, CDCl3) δ 7.66 (dd, J = 10.4, 6.1 Hz,
3H), 7.61−7.51 (m, 2H), 7.44 (dd, J = 5.1, 3.7 Hz, 1H), 7.25 (d, J =
8.1 Hz, 3H), 5.50 (q, J = 6.9 Hz, 1H), 2.41 (s, 3H), 1.53 (d, J = 6.9 Hz,
3H); HRMS ESI (m/z) calcd for C17H15F3NaO4S [MNa]+ 395.0535,
found 395.0528.
1-Oxo-1-(thiophen-2-yl)propan-2-yl 4-Methylbenzenesulfonate
(4g).8 The title compound was obtained as a white solid (81%
yield) according to the general α-tosyloxy ketone formation
procedure; 1H NMR (300 MHz, CDCl3) δ 7.90 (d, J = 3.9 Hz,
1H), 7.78 (d, J = 8.3 Hz, 2H), 7.73 (d, J = 4.9 Hz, 1H), 7.30 (d, J = 8.8
Hz, 2H), 7.21−7.12 (m, 1H), 5.48 (q, J = 6.9 Hz, 1H), 2.44 (s, 3H),
1.62 (d, J = 6.9 Hz, 3H); HRMS ESI (m/z) calcd for C14H14NaO4S2
[MNa]+ 333.0226, found 333.0229.
1-Oxo-1-phenylpropan-2-yl 4-Methylbenzenesulfonate (2).7c
General α-Tosyloxy Ketone Formation Procedure. [Hydroxy-
(tosyloxy)iodo]benzene (0.33 mmol) was added to a solution of 1a
(0.3 mmol) in acetonitrile (1.5 mL). The mixture was stirred at 40 °C
until disappearance of the suspension. The reaction mixture was
poured into water (15 mL) and extracted thrice with dichloromethane
(10 mL). The combined organics layers were dried over MgSO4 and
evaporated under reduced pressure. The crude mixture was purified by
column chromatography on silica gel with EtOAc:hexanes (20:80) to
2-Oxo-1,2-diphenylethyl 4-Methylbenzenesulfonate (4h).8 The
title compound was obtained as a white solid (35% yield) according to
1
the general α-tosyloxy ketone formation procedure; H NMR (300
MHz, CDCl3) δ 7.87 (d, J = 7.2 Hz, 2H), 7.74 (d, J = 8.3 Hz, 2H),
7.54 (t, J = 7.4 Hz, 1H), 7.45−7.35 (m, 4H), 7.32 (q, J = 3.8 Hz, 3H),
7.24 (d, J = 8.3 Hz, 2H), 6.70 (s, 1H), 2.42 (s, 3H); HRMS ESI (m/z)
calcd for C21H18NaO4S [MNa]+ 389.0818, found 389.0825.
1
provide 85.8 mg (92% yield) of 2 as a white solid; H NMR (300
MHz, CDCl3) δ 7.86 (d, J = 7.0 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H),
7.58 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.25 (d, J = 8.1 Hz,
2H), 5.78 (q, J = 7.0 Hz, 1H), 2.39 (s, 3H), 1.58 (d, J = 7.0 Hz, 3H);
HRMS ESI (m/z) calcd for C16H16NaO4S [MNa]+ 327.0661, found
327.0658.
1,2,3,4-Tetrahydro-1-oxonaphthalen-2-yl 4-Methylbenzenesulfo-
nate (4i).8 The title compound was obtained as a brown solid (25%
yield) according to the general α-tosyloxy ketone formation
1
procedure; H NMR (300 MHz, CDCl3) δ 7.93 (dd, J = 11.5, 8.1
1-Oxo-1-phenylbutan-2-yl 4-Methylbenzenesulfonate (4a).7b
The title compound was obtained as a colorless solid (91% yield)
Hz, 2H), 7.50 (td, J = 7.4, 1.1 Hz, 1H), 7.43−7.29 (m, 3H), 7.25 (t, J =
7.7 Hz, 1H), 5.16 (dd, J = 12.2, 5.0 Hz, 1H), 3.12 (dd, J = 6.2, 3.5 Hz,
2H), 2.55 (dt, J = 13.4, 4.5 Hz, 1H), 2.50−2.31 (m, 4H); HRMS ESI
(m/z) calcd for C17H16NaO4S [MNa]+ 339.0662, found 339.0666.
2-Oxocyclohexyl 4-Methylbenzenesulfonate (4j).18 The title
compound was obtained as a white solid (74% yield) according to
1
according to the general α-tosyloxy ketone formation procedure; H
NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 8.2, 1.0 Hz, 2H), 7.74 (d, J =
8.3 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.25 (t,
J = 7.0 Hz, 2H), 5.55 (dd, J = 7.9, 5.0 Hz, 1H), 2.39 (s, 3H), 2.05−
1.83 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H); HRMS ESI (m/z) calcd for
C17H18NaO4S [MNa]+ 341.0818, found 341.0810.
1
the general α-tosyloxy ketone formation procedure; H NMR (400
MHz, CDCl3) δ 7.82 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H),
4.89 (dd, J = 10.9, 5.9 Hz, 1H), 2.53 (d, J = 13.8 Hz, 2H), 2.43 (s, 3H),
2.37−2.21 (m, 2H), 2.02−1.82 (m, 2H), 1.77−1.57 (m, 2H); HRMS
ESI (m/z) calcd for C13H16NaO4S [MNa]+ 291.0662, found 291.0658.
5,5-Dimethyl-4-oxo-1-phenylhexan-3-yl 4-Methylbenzenesulfo-
nate (4k). The title compound was obtained as a colorless oil (93%
yield) according to the general α-tosyloxy ketone formation
1-Oxo-1-phenyloctan-2-yl 4-Methylbenzenesulfonate (4b).7b The
title compound was obtained as a light brown solid (89% yield)
1
according to the general α-tosyloxy ketone formation procedure; H
NMR (400 MHz, CDCl3) δ 7.88−7.78 (m, 2H), 7.77−7.68 (m, 2H),
7.62−7.52 (m, 1H), 7.44 (dd, J = 10.8, 4.8 Hz, 2H), 7.24 (t, J = 6.7 Hz,
2H), 5.58 (dd, J = 8.2, 4.9 Hz, 1H), 2.39 (s, 3H), 1.96−1.74 (m, 2H),
1.48−1.37 (m, 1H), 1.33 (ddd, J = 12.6, 9.2, 5.0 Hz, 1H), 1.27−1.11
1
procedure; Rf = 0.25 (10% EtOAc/hexanes); H NMR (300 MHz,
E
DOI: 10.1021/acs.joc.5b00948
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
CDCl3) δ 7.84 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 7.27 (dt, J
= 14.9, 6.9 Hz, 3H), 7.12 (d, J = 6.9 Hz, 2H), 5.34 (dd, J = 7.2, 4.6 Hz,
1H), 2.89−2.70 (m, 1H), 2.68−2.53 (m, 1H), 2.48 (s, 3H), 2.02 (ddd,
J = 12.3, 5.8, 2.0 Hz, 2H), 1.10 (s, 9H); 13C NMR (75 MHz, CDCl3)
209.3, 145.0, 140.0, 133.7, 129.8, 128.6, 128.5, 128.0, 126.4, 78.0, 43.7,
34.0, 31.1, 26.7, 21.7; IR (neat) 2969, 1720, 1496, 1368, 1189, 1176,
932, 553 cm−1; HRMS ESI (m/z) calcd for C21H26NaO4S [MNa]+
397.1444, found 397.1449.
Cui, J.; Hou, X.-S.; Liu, S.-S.; Gao, W.-C.; Jiang, S.; Tian, J.; Zhang, C.
Tetrahedron: Asymmetry 2011, 22, 2039.
̀
(9) (a) Ther
́
ien, M.-E.; Guilbault, A.-A.; Legault, C. Y. Tetrahedron:
Asymmetry 2013, 24, 1193. (b) Guilbault, A.-A.; Basdevant, B.; Wanie,
V.; Legault, C. Y. J. Org. Chem. 2012, 77, 11283. (c) Guilbault, A.-A.;
Legault, C. Y. ACS Catal. 2012, 2, 219.
(10) Moriarty, R. M.; Penmasta, R.; Awasthi, A. K.; Epa, W. R.;
Prakash, I. J. Org. Chem. 1989, 54, 1101.
(11) (a) Wei, S.; Pedroni, J.; Meißner, A.; Lumbroso, A.; Drexler, H.-
J.; Heller, D.; Breit, B. Chem.Eur. J. 2013, 19, 12067. (b) Nishiumi,
M.; Miura, H.; Wada, K.; Hosokawa, S.; Inoue, M. Adv. Synth. Catal.
2010, 352, 3045. (c) Gooßen, L. J.; Gooßen, K.; Rodriguez, N.;
Blanchot, M.; Linder, C.; Zimmermann, B. Pure Appl. Chem. 2008, 80,
1725. (d) Dragutan, V.; Dragutan, I.; Delaude, L.; Demonceau, A.
Coord. Chem. Rev. 2007, 251, 765. (e) Ye, S.; Leong, W. K. J.
Organomet. Chem. 2006, 691, 1216. (f) Bruneau, C.; Dixneuf, P. H.
Angew. Chem., Int. Ed. 2006, 45, 2176.
(12) Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto,
K. J. Am. Chem. Soc. 2005, 127, 12244.
(13) Shriver, D. F.; Drezdzon, M. A. The Manipulation of Air-Sensitive
Compounds, 2nd ed.; Wiley: New York, 1986.
ASSOCIATED CONTENT
■
S
* Supporting Information
NMR spectra for all new compounds. The Supporting
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc.5b00948.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: claude.legault@usherbrooke.ca.
Notes
(14) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
(15) Eames, J.; Coumbarides, G. S.; Suggate, M. J.; Weerasooriya, N.
Eur. J. Org. Chem. 2003, 634.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(16) Zhu, Y.; Shu, L.; Tu, Y.; Shi, Y. J. Org. Chem. 2001, 66, 1818.
(17) Noji, M.; Ohno, T.; Fuji, K.; Futaba, N.; Tajima, H.; Ishii, K. J.
Org. Chem. 2003, 68, 9340.
(18) John, O. R. S.; Killeen, N. M.; Knowles, D. A.; Chak Yau, S.;
Bagley, M. C.; Tomkinson, N. C. O. Org. Lett. 2007, 9, 4009.
■
This work was supported by the National Science and
Engineering Research Council (NSERC) of Canada, the
Canada Foundation for Innovation (CFI), the FQRNT Centre
in Green Chemistry and Catalysis (CGCC), and the Universite
de Sherbrooke. We thank Antoine Jobin-Des Lauriers for
helpful discussions.
́
REFERENCES
■
(1) (a) Uyanik, M.; Ishihara, K. Chem. Commun. 2009, 2086.
(b) Zhdankin, V. V. Arkivoc 2009, 1, 1. (c) Wirth, T. Angew. Chem., Int.
Ed. 2005, 44, 3656 and references cited therein. (d) Tohma, H.; Kita,
Y. In Hypervalent Iodine Chemistry; Wirth, T., Ed.; Springer: Berlin,
2003; p 209. (e) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
2523. (f) Moriarty, R. M.; Prakash, O. Org. React. 2001, 57, 327.
(g) Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic
Press: San Diego, 1997.
(2) Reviews on the catalytic generation of hypervalent iodine:
(a) Singh, F. V.; Wirth, T. Chem.Asian J. 2014, 9, 950. (b) Dohi, T.;
Kita, Y. Chem. Commun. 2009, 2073. (c) Richardson, R. D.; Wirth, T.
Angew. Chem., Int. Ed. 2006, 45, 4402.
(3) Reviews on hypervalent iodine-mediated asymmetric trans-
formations: (a) Berthiol, F. Synthesis 2015, 47, 587. (b) Parra, A.;
Reboredo, S. Chem.Eur. J. 2013, 19, 17244. (c) Ngatimin, M.;
Lupton, D. W. Aust. J. Chem. 2010, 63, 653.
(4) Reviews on hypervalent iodine-mediated functionalization of
carbonyl compounds: (a) Dong, D.-Q.; Hao, S.-H.; Wang, Z.-L.; Chen,
C. Org. Biomol. Chem. 2014, 12, 4278. (b) Merritt, E. A.; Olofsson, B.
Synlett 2011, 517.
(5) Neilands, O.; Karele, B. Zh. Org. Khim. 1970, 6, 885.
(6) (a) Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.;
Wettbach, R. H. J. Org. Chem. 1982, 47, 2487. (b) Koser, G. F.;
Wettach, R. H. J. Org. Chem. 1977, 42, 1476.
(7) (a) Farooq, U.; Schafer, S.; Shah, A. A.; Freudendahl, D. M.;
̈
Wirth, T. Synthesis 2010, 1023. (b) Altermann, S. M.; Richardson, R.
D.; Page, T. K.; Schmidt, R. K.; Holland, E.; Mohammed, U.; Paradine,
S. M.; French, A. N.; Richter, C.; Bahar, A. M.; Witulski, B.; Wirth, T.
Eur. J. Org. Chem. 2008, 5315. (c) Richardson, R. D.; Page, T. K.;
Altermann, S. M.; Paradine, S. M.; French, A. N.; Wirth, T. Synlett
2007, 538. (d) Hirt, U. H.; Schuster, M. F. H.; French, A. N.; Wiest,
O. G.; Wirth, T. Eur. J. Org. Chem. 2001, 1569. (e) Hirt, U. H.;
Spingler, B.; Wirth, T. J. Org. Chem. 1998, 63, 7674.
(8) (a) Brenet, S.; Berthiol, F.; Einhorn, J. Eur. J. Org. Chem. 2013,
8094. (b) Rodriguez, A.; Moran, W. J. Synthesis 2012, 1178. (c) Yu, J.;
F
DOI: 10.1021/acs.joc.5b00948
J. Org. Chem. XXXX, XXX, XXX−XXX