Iodide-Mediated Synthesis of Spirooxindolo Dihydrofurans from Iodonium Ylides and 3-Alkylidene-2-oxindoles

Article abstract of DOI:10.1021/acs.joc.7b01639

An iodide-mediated reaction between cyclic iodonium ylides of 1,3-dicarbonyls and 3-alkylidene-2-oxindoles results in 3H-spiro[furan-2,3′-indolin]-2′-ones. The reaction was tolerant to substitutions on both the alkylidene and ylide substrates and provided

Full text of DOI:10.1021/acs.joc.7b01639

Note
pubs.acs.org/joc
Iodide-Mediated Synthesis of Spirooxindolo Dihydrofurans from
Iodonium Ylides and 3‑Alkylidene-2-oxindoles
Benjamin A. Laevens, Jason Tao, and Graham K. Murphy*
Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L3G1, Canada
S
* Supporting Information
ABSTRACT: An iodide-mediated reaction between cyclic
iodonium ylides of 1,3-dicarbonyls and 3-alkylidene-2-oxindoles
results in 3H-spiro[furan-2,3′-indolin]-2′-ones. The reaction
was tolerant to substitutions on both the alkylidene and ylide
substrates and provided access to 19 new, densely functionalized
polycyclic spirocycles in typically high yield.
odonium ylides of 1,3-dicarbonyls are an important class of
Isynthetically useful hypervalent iodine (HVI) compounds
that can be synthesized easily from active methylene
compounds and PhI(OAc)2.1 Iodonium ylides of cyclic 1,3-
dicarbonyls are generally easier to isolate and handle, more
thermally stable,2 and more soluble in common organic
solvents than the acyclic counterparts. Such ylides can be
used in a variety of different reactions, including with
nucleophiles,3 as diazo surrogates in carbenoid reactions,4 and
in cycloaddition reactions.5 Suitable dipolarophiles for cyclo-
addition reactions include alkenes,6 alkynes,7 arynes,5a ketenes,8
isocyanates,5c isothiocyanates,5c nitriles,5b CS2,5c and carbodii-
mides,9 which can provide access to a variety of polycyclic
synthetic building blocks with carbocyclic or heterocyclic
scaffolds.
Reactions between iodonium ylides and functionalized
dipolarophiles can result in new methods for preparing valuable
classes of compounds, such as spirocyclic oxindoles. The family
of compounds containing (or derived from) 3,3′-spirooxindolo
dihydrofurans are represented by a variety of naturally
occurring compounds10 (Figure 1a). Previous preparations of
this motif employed diazo chemistry,11 intramolecular cycliza-
Figure 1. Motivation, background, and synthetic plan for a new 3,3′-
tions,12 [3 + 2] cycloadditions,13 intramolecular Friedel−Crafts
reactions,14 and annulation strategies.15 As part of our
investigations of iodonium ylides acting as diazo surrogates,16
we recently discovered that iodonium ylides react with
electron-rich styrenes, under the action of PhI(OAc)2 and
Bu4NI, to give dihydrofurans (Figure 1b).17 We envisioned that
more rigid, cyclic iodonium ylides (e.g., 2a) would react with 3-
alkylidene-2-oxindoles (1) to generate 3,3′-spirooxindolo
dihydrofurans. This chemistry would offer a mild, metal-free
and environmentally benign alternative to existing method-
ologies, and we report here that under Bu4NI catalysis, cyclic
iodonium ylides react with alkenes (1) to chemo-, diastereo-,
and regioselectively generate spirocyclic dihydrofurans 3
(Figure 1c).
spirooxindolo dihydrofuran synthesis.
We began this investigation using the previously optimized
reactions conditions (Figure 1, b), anticipating recovery of two
possible regioisomeric dihydrofurans 3a and/or 3a′ (Table 1,
entry 1). Complete consumption of 1a was observed within 5
h; however, the product was only recovered in 64% yield.
Presuming the excess PhI(OAc)2 to be problematic, we
decreased its loading and recovered 3a in 83% yield (entry
Special Issue: Hypervalent Iodine Reagents
Received: July 3, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.7b01639
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization of the Reaction
Figure 2. Structural elucidation of the spirooxindolo dihydrofuran
product. (a) Diagnostic 13C NMR peaks. (b) COSY (green) and
HMBC (blue) peaks, and the missing key peak (red). (c) X-ray
structure of 3a.
PhI(OAc)2
(equiv)
Bu4NI
time
(h)
b
,
c
b
entry
(equiv)
conv.
yield
1
2
1.0
0.3
0.3
0.3
0.3
0.3
−
0.3
0.3
0.3
0.3
0.3
0.3
−
5
5
100%
>95%
42%
64%
83%
d
3
5
38%
d
4
25
5
60%
54%
range H−H coupling between the 4.33 ppm methine proton
and the 2.53 ppm diasterotopic methylene (Figure 2b, green
arrow) are consistent with 3a. HMBC crosspeaks from the
methine proton showed all the expected 2- and 3-bond
correlations (Figure 2b, blue arrows) except the crucial 193.2
ppm crosspeak, which would have distinguished between 3a
and 3a′. The product was crystallized from CH2Cl2 (4 °C, 16
h), and X-ray analysis proved the structure and stereochemistry
to be as shown in Figure 2c. This regioisomer is consistent with
previous dihydrofuran syntheses employing iodonium ylides,
with the oxygen bound to the more substituted of alkene
carbons.19
e
5
63%
46%
f
6
5
>95%
8%
78%
7
5
<5%
8
0.3
−
5
19%
10%
9
−
−
−
−
−
−
0.3
0.1
0.3
0.3
0.3
0.3
5
83%
81%
10
11
20
20
5
54%
48%
>95%
>95%
>95%
100%
94%
g
12
96%
h
13
g,i
3
93%
14
1
97% (91%)
a
Reaction Conditions: 1a (0.1 mmol) is combined with 2a,
PhI(OAc)2, and Bu4NI in solvent (0.1 M), and the reaction is stirred
Having optimized the reaction, we conducted it at the 1.0
mmol scale, where 3a was recovered in 90% yield (Scheme 1).
The N-CBZ (1b), N-Boc (1c), and N-Ts derivatives gave
products 3b, 3c, and 3d in 90%, 99%, and 90% yields,
respectively. Changing the polarity of the N-substituent from
electron-withdrawing to electron-donating groups was also
acceptable, as the N-Bn (1e), N-allyl (1f), and N-Me (1g)
substrates gave products 3e, 3f, and 3g in 97%, 85%, and 98%
yields, albeit over longer reaction times. Halogenated
alkylidenes possessing either N-Me (5-F, 1h), (5-Cl, 1i), or
(5-Br, 1j) or N-Boc (5-F, 1k), (5-Cl, 1l), or (5-Br, 1m)
substituents also gave the desired products in generally high
yield. Benzoyl and acetyl alkylidene substituents were tested
and gave 3n and 3o in 99% and 89% yields. Lastly, an electron-
neutral phenyl substituent on the alkylidene was tested, and it
gave 3p in 82% yield. This is noteworthy since the switch from
electron-poor to electron-neutral alkylidene substituents failed
to alter the regioisomeric outcome (e.g., 3p vs 3p′) of the
reaction.
We investigated other cyclic iodonium ylides in the reaction
with alkylidene 1a, and the iodonium ylide of cyclohexane
dione (2b) gave the dihydrofuran in 97% yield (Scheme 2).
Meldrum’s acid iodonium ylide (2c) failed, but a β-ketoester-
derived ylide (2d) gave 3s in 54% yield, with the ester carbonyl
participating in dihydrofuran formation. Lastly, the pyrimidine
derived iodonium ylide 2e gave 3t in 45% yield.
We attempted to circumvent isolation of the iodonium ylide
by developing a one-pot, multistep synthesis of 3a, with in situ
generation of 2a (eq 1).1b,21 Alkene 1a was combined with
dimedone, PhI(OAc)2, Bu4NI, and Cs2CO3 and stirred at 60 °C
in CH3CN. Though the alkene was consumed, no trace of 3a
was observed. We believe the alkene decomposition occurred
at the indicated temperature for the indicated length of time.
b
1
Conversion and yield determined by H NMR, using hexamethyldi-
c
siloxane as internal standard. Conversions listed as >95% indicate that
d
<5 mol % of 1a remained according to 1H NMR. Solvent was DCM.
e
f
g
Solvent was DCE. Solvent was toluene. Reaction at 60 °C.
h
i
Reaction at reflux. 1.1 equiv 2a used.
2). Changing the solvent offered no improvement, with
incomplete conversion observed even after 25 h (entries 3−
6). A control experiment lacking both PhI(OAc)2 and Bu4NI
failed (entry 7), and while the reaction containing 0.3 equiv of
PhI(OAc)2 also failed (10% yield, entry 8), the reaction
proceeded in 81% yield when only Bu4NI was present. Though
the conversion decreased when PhI(OAc)2 was omitted
(compare entry 9 with entry 2), the yield of 3a was nearly
equal in both instances. Decreasing the loading of Bu4NI
resulted in decreased conversion, but a longer reaction gave the
product in 94% NMR yield (entries 10, 11). Increasing the
temperature to either 60 °C or reflux resulted in decreased
reaction times (entries 12, 13), and despite the elevated
temperature, we did not observe any of iodoether 4, a known
byproduct of thermal reactions of 2a.5b,18 Incomplete
consumption of 1a was still problematic, but increasing the
loading of 2a to 1.1 equiv resulted in complete consumption of
1a, with 3a observed in 97% NMR yield (91% isolated, entry
14). Thus, straightforward synthesis of spirooxindolo dihy-
drofurans could be achieved using nearly equimolar loading of
ylide and alkene.
NMR analysis of the product indicated that the reaction
proceeded chemoselectively to give 3a as the sole product.20
The 87.8 ppm 13C peak (4°, R3C−O) (Figure 2a) and the long-
B
DOI: 10.1021/acs.joc.7b01639
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Scheme 1. Synthesis of Spirooxindolo Dihydrofurans
yield), and with I2, which failed (see Table SI-2). It is
improbable that thermally or photochemically generated free
carbenes are involved since the reaction proceeds well at room
temperature, and since iodoether 4 was not observed.5b,18 The
intermediacy of cyclopropanes is also unlikely because these do
not readily rearrange to dihydrofurans.19 To test for radical
chemistry, we added BHT (0.3 equiv), but 3a was still
recovered in 95% yield. Adding DDQ (0.3 equiv) completely
consumed ylide 2a, presumably though chemical degradation.
We therefore propose an ionic mechanism22 in which iodide
activates ylide 2a, giving A (Figure 3). Ligand exchange with
a
Reaction conditions: Alkene 1 (0.3 mmol, 1 equiv) is combined with
2a (1.1 equiv) and Bu4NI (0.3 equiv) in CH3CN (0.1 M), and the
b
reaction is stirred at reflux. Reaction carried out at the 1.0 mmol scale.
c
1H NMR yield using hexamethyldisiloxane as internal standard.
Scheme 2. Synthesis of Spirooxindolo Dihydrofurans Using
Cyclic Iodonium Ylides of 1,3-Dicarbonyls
Figure 3. Proposed mechanism for the formation of 3a.
the nucleophilic vinylogous enamine gives B.23 Steric repulsion
with the stereogenic methine substituents prevents bond
rotation, forcing the C−O bond to be forged from the α-
face, giving C as a single diastereomer. Reductive elimination of
iodobenzene from C generates 3a. We believe the differing
reactivity observed for cyclic and acyclic17 iodonium ylides with
1 (e.g., dihydrofuran vs cyclopropane formation) stems from
(a) the fixed proximity of the cyclic enolate oxygen atom with
the electrophile (see B) and (b) the unfavorable steric
interactions necessary for cyclopropane formation to occur.
In conclusion, we report here a novel, metal-free synthesis of
spirooxindolo dihydrofurans from substituted 3-alkylidene-2-
oxindoles and iodonium ylides of 1,3-dicarbonyls. The
optimized procedure was catalyzed by Bu4NI and provided
the desired spirocycles in excellent yield. The reaction was
tolerant to both electron-rich and electron-poor substituents on
the oxindole as well as keto, ester, and aryl substituents on the
alkylidene. Variations in the iodonium ylide were also tolerated,
with ylides derived from cyclic 1,3-diketones, 1,3-ketoesters,
and pyrimidines all undergoing the spirocycle formation.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out in flame-dried
glassware under a nitrogen atmosphere. Transfer of anhydrous
solvents and reagents was accomplished with oven-dried syringes.
Thin-layer chromatography was performed on glass plates precoated
with 0.25 mm Kieselgel 60 F254. Flash chromatography columns were
packed with 230−400 mesh silica gel. Melting points were recorded on
a MEL-TEMP II instrument and are uncorrected. Proton NMR
due to an undesired side reaction with PhI(OAc)2, as previously
observed (see Table 1, entry 1).
We probed the reaction mechanism by substituting Bu4NI
with NaI (55% yield), Bu4NBr (31% yield), Bu4NCl (17%
C
DOI: 10.1021/acs.joc.7b01639
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
spectra (1H NMR) were recorded at 300 or 500 MHz and are reported
(ppm) relative to the residual chloroform peak (7.26 ppm), and
coupling constants (J) are reported in hertz (Hz). Carbon NMR
spectra (13C NMR) were recorded at 125 MHz and are reported
(ppm) relative to the center line of the triplet from chloroform-d (77.0
ppm). 19F NMR spectra were recorded at 282 MHz and are reported
relative to TFA. Positive ion electrospray (ESI) mass spectrometry
experiments were performed with a ThermoFisher Scientific Q-
Exactive Orbitrap hybrid mass spectrometer, with accurate mass
determinations performed at a mass resolution of 70,000. For ESI,
samples were infused at 10 μL/min in 1:1 CH3OH/H2O + 0.1%
formic acid.
7.7 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.41 (dd, J = 7.6, 7.6 Hz, 1H),
7.91 (d, J = 8.3 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.6, 28.0
(4C), 28.9, 34.6, 37.6, 50.8, 53.4, 61.3, 85.3, 87.5, 111.5, 115.4, 122.6,
124.8, 125.4, 131.7, 140.3, 148.6, 167.9, 171.5, 177.0, 193.2; HRMS
(ESI) calcd for C25H30O7N [M + H]+ 456.2017; found 456.2016.
3d. General Procedure A was followed using 1d (111 mg, 0.3
mmol). The reaction was complete after 1 h at 60 °C, and 3d was
recovered as an orange solid (138 mg) in 90% yield. Rf = 0.27 (40%
EtOAc/hexanes, UV active); m.p.: 117−118 °C; IR (ATR): 2960,
1770, 1739, 1651, 1606, 1464, 1384, 1178, 1161 cm−1; 1H (500 MHz,
CDCl3) δ 0.75 (t, J = 7.1 Hz, 3H), 1.13 (s, 3H), 1.19 (s, 3H), 2.27 (d,
JAB = 16.3 Hz, 1H), 2.31 (d, JAB = 16.3 Hz, 1H), 2.39 (d, JAB = 17.8 Hz,
1H), 2.42 (s, 3H), 2.44 (d, JAB = 17.8 Hz, 1H), 3.72 (m, 2H), 4.11 (s,
1H), 7.15 (dd, J = 7.6, 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.33 (d, J
= 8.2 Hz, 2H), 7.44 (dd, J = 7.9, 7.9 Hz, 1H), 7.91 (d, J = 8.3 Hz, 1H),
7.94 (d, J = 8.3 Hz, 2H); 13C{1H} (125 MHz, CDCl3) δ 13.5, 21.7,
28.0, 28.6, 34.6, 37.4, 50.7, 53.5, 61.3, 87.3, 111.1, 113.8, 122.9, 125.2,
125.7, 127.9 (2C), 129.9 (2C), 132.0, 134.3, 139.4, 146.3, 167.3, 171.4,
177.0, 193.1; HRMS (ESI) calcd for C27H28O7NS [M + H]+ 510.1581;
found 510.1581.
3e. General Procedure A was followed using 1e (92 mg, 0.3 mmol).
The reaction was complete after 4 h at 60 °C, and 3e was recovered as
a white solid (130 mg) in 97% yield. Rf = 0.33 (40% EtOAc/hexanes,
UV active); m.p.: 151−153 °C, IR (ATR): 2966, 2929, 1728, 1641,
1611, 1489, 1468, 1397, 1376, 1365, 1351, 1233, 1180 cm−1; 1H (500
MHz, CDCl3) δ 0.74 (t, J = 7.2, 3H), 1.20 (s, 3H), 1.25 (s, 3H), 2.34
(d, JAB = 16.3 Hz, 1H), 2.38 (d, JAB = 16.3 Hz, 1H), 2.47 (d, JAB = 17.7
Hz, 1H), 2.54 (d, JAB = 17.7 Hz, 1H), 3.79 (m, 2H), 4.41 (s, 1H), 4.78
(d, J = 15.9 Hz, 1H), 5.06 (d, J = 15.9 Hz, 1H), 6.69 (d, J = 7.9 Hz,
1H), 7.00 (dd, J = 7.6, 7.6 Hz, 1H), 7.24 (dd, J = 7.9, 7.9 Hz, 1H), 7.30
(m, 6H); 13C{1H} (125 MHz, CDCl3) δ 13.5, 28.1, 28.9, 34.6, 37.7,
43.9, 50.9, 53.0, 61.1, 87.8, 109.7, 111.6, 123.1, 124.1, 125.6, 127.0
(2C), 127.9, 128.9 (2C), 131.2, 134.7, 143.0, 168.0, 173.5, 177.1,
193.2; HRMS (ESI) calcd for C27H28O5N [M + H]+ 446.1962; found
446.1961.
The 3-alkylidene-2-oxindoles 2a−o were prepared by Wittig
olefinations of the isatins.24 Compounds 2p was prepared by aldol
condensation of benzaldehyde onto N-acetyl-2-oxindole.
General Procedure A: Dihydrofuran Synthesis. The alkylidene
1 (0.3 mmol, 1.0 equiv) was added to a flame-dried round-bottom
flask equipped with a magnetic stir bar and a septum, and to this was
added CH3CN (3.0 mL, 0.1 M). To this was added Bu4NI (33 mg,
0.09 mmol, 0.3 equiv), followed by 2a (113 mg, 0.33 mmol, 1.1 equiv),
and the reaction was immersed in a preheated 60 °C oil bath. The
resulting mixture was stirred until TLC analysis (eluting with 40%
EtOAc in hexanes) indicated consumption of 1. Upon completion, the
CH3CN was evaporated by rotary evaporation, and the resulting
residue was dissolved in a minimum volume of CH2Cl2 and charged
onto a silica gel column. The product was eluted using a gradient of
10, 20, 30, then 40% EtOAc in hexanes, and the recovered product was
azeotropically dried using chloroform, reconcentrated, and dried under
high vacuum.
3a. General Procedure A was followed using 1a (78 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3a was recovered as
a white solid (109 mg) in 91% yield.
General Procedure A was also followed using 1a (259 mg, 1.0
mmol). The reaction was complete after 1 h at 60 °C, and 3a was
recovered as a white solid (356 mg) in 90% yield. Rf = 0.40 (40%
EtOAc/hexanes, UV active); m.p.: 146−148 °C; IR (ATR): 2958,
1771, 1737, 1717, 1646, 1175, 1166 cm−1;1H NMR (500 MHz,
CDCl3) δ 0.84 (t, J = 7.2 Hz, 3H), 1.20 (s, 3H), 1.26 (s, 3H), 2.35 (d,
JAB = 16.3 Hz, 1H), 2.39 (d, JAB = 16.3 Hz, 1H), 2.48 (d, JAB = 17.7 Hz,
1H), 2.52 (d, JAB = 17.7 Hz, 1H), 2.71 (s, 3H), 3.83 (m, 2H), 4.33 (br
s, 1H), 7.21 (dd, J = 7.7, 7.7 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.45
(dd, J = 8.0, 8.0 Hz, 1H), 8.26 (d, J = 8.3 Hz, 1H); 13C{1H} NMR
(125 MHz, CDCl3) δ 13.6, 26.5, 28.1, 28.8, 34.7, 37.6, 50.9, 53.6, 61.5,
87.7, 111.5, 116.9, 122.9, 125.3, 125.6, 131.8, 140.5, 167.6, 170.2,
174.0, 176.9, 193.2; HRMS (ESI) calcd for C22H24O6N [M + H]+
398.1604; found 398.1599.
3b. General Procedure A was followed using 1b (105 mg, 0.3
mmol). The reaction was complete after 1 h at 60 °C, and 3b was
recovered as a white solid (132 mg) in 90% yield. Rf = 0.37 (40%
EtOAc/hexanes, UV active); m.p.: 116−118 °C; IR (ATR): 2963,
1777, 1742, 1645, 1608, 1344, 1286, 1231, 1169 cm−1; 1H NMR (500
MHz, CDCl3) δ 0.83 (t, J = 7.2 Hz, 3H), 1.19 (s, 3H), 1.24 (s, 3H),
3f. General Procedure A was followed using 1f (68 mg, 0.3 mmol).
The reaction was complete after 4 h at 60 °C, and 3f was recovered by
column chromatography, eluting with 5, 10, 20, and then 30% EtOAc/
hexanes, which gave a white solid (101 mg) in 85% yield. Rf = 0.29
(40% EtOAc/hexanes, UV active); m.p.: 173−174 °C; IR (ATR):
2961, 1736, 1726, 1648, 1613, 1465, 1395, 1366, 1226, 1184, 1169
cm−1; 1H (500 MHz, CDCl3) δ 0.80 (t, J = 7.1 Hz, 3H), 1.17 (s, 3H),
1.23 (s, 3H), 2.33 (s, 2H), 2.43 (d, JAB = 17.7 Hz, 1H), 2.50 (d, JAB
=
17.7 Hz, 1H), 3.81 (m, 2H), 4.24 (dd, J = 16.7, 4.5 Hz, 1H), 4.31 (s,
1H), 4.41 (dd, J = 16.7, 4.5 Hz, 1H), 5.23 (d, J = 13.1 Hz, 2H), 5.83
(m, 1H), 6.82 (d, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 7.25
(d, J = 7 Hz, 1H), 7.32 (dd, J = 7.7, 7.7 Hz, 1H); 13C{1H} (125 MHz,
CDCl3) δ 13.5, 28.0, 28.9, 34.6, 37.6, 42.3, 50.8, 52.8, 61.1, 87.7, 109.5,
111.6, 117.6, 123.1, 123.9, 125.6, 130.3, 131.3, 143.1, 168.1, 173.0,
177.1, 193.2; HRMS (ESI) calcd for C23H26O5N [M + H]+ 396.1806;
found 396.1806.
3g. General Procedure A was followed using 1g (69 mg, 0.3 mmol).
The reaction was complete after 6 h at 60 °C, and 3g was recovered as
an oil that solidified upon standing (108 mg) in 98% yield. Rf = 0.23
(40% EtOAc/hexanes, UV active); m.p.: 102−103 °C; IR (ATR):
2970, 2930, 1736, 1636, 1612, 1467, 1347, 1187 cm−1; 1H (500 MHz,
CDCl3) δ 0.85 (t, J = 7.2 Hz, 3H), 1.18 (s, 3H), 1.23 (s, 3H), 2.33 (s,
2H), 2.43 (d, JAB = 17.7 Hz, 1H), 2.50 (d, JAB = 17.7 Hz, 1H), 3.21 (s,
3H), 3.84 (q, J = 7.2 Hz, 2H), 4.26 (s, 1H), 6.84 (d, J = 7.9 Hz, 1H),
7.04 (dd, J = 7.6, 7.6 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 7.37 (dd, J =
7.8, 7.8 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.6, 26.5, 27.9, 28.9,
34.6, 37.6, 50.8, 52.5, 61.1, 87.8, 108.6, 111.8, 123.1, 123.8, 125.6,
131.4, 144.1, 168.3, 173.2, 177.1, 193.2; HRMS (ESI) calcd for
C21H24O5N [M + H]+ 370.1649; found 370.1648.
2.33 (d, JAB = 16.3 Hz, 1H), 2.36 (d, JAB = 16.3 Hz, 1H), 2.45 (d, JAB
=
17.7 Hz, 1H), 2.50 (d, JAB = 17.7 Hz, 1H), 3.82 (m, 2H), 4.32 (s, 1H),
5.46 (s, 2H), 7.18 (dd, J = 7.8, 7.8 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H),
7.37 (d, J = 7.2 Hz, 1H), 7.42 (m, 3H), 7.51 (d, J = 6.9 Hz, 2H), 7.97
(d, J = 8.3 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 13.6, 28.1,
28.8, 34.7, 37.6, 50.9, 53.5, 61.4, 69.2, 87.5, 111.5, 115.5, 122.8, 125.2,
125.5, 128.2 (2C), 128.70, 128.74 (2C), 131.8, 134.4, 139.7, 150.2,
167.8, 171.3, 176.9, 193.2; HRMS (ESI) calcd for C28H28O7N [M +
H]+ 490.1860; found 490.1860.
3c. General Procedure A was followed using 1c (95 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3c was recovered by
column chromatography, eluting with 10, 20, and then 30% EtOAc/
hexanes, which gave an oil that solidified upon standing (136 mg) in
99% yield. Rf = 0.39 (40% EtOAc/hexanes, UV active); m.p.: 138−140
°C; IR (ATR): 2965, 1787, 1730, 1652, 1470, 1347, 1292, 1151 cm−1;
1H (500 MHz, CDCl3) δ 0.85 (t, J = 7.2 Hz, 3H), 1.18 (s, 3H), 1.23
(s, 3H), 1.63 (s, 9H), 2.33 (s, 2H), 2.44 (d, JAB = 17.7 Hz, 1H), 2.50
(d, JAB = 17.7 Hz, 1H), 3.83 (m, 2H), 4.23 (s, 1H), 7.14 (dd, J = 7.7,
3h. General Procedure A was followed using 1h (83 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3h was observed in
87% NMR yield. An analytically pure sample was recovered by column
chromatography, eluting with 5, 10, 15, 20, and then 30% EtOAc/
hexanes, which gave a pale-yellow solid that was characterized. Rf =
0.45 (40% EtOAc/hexanes, UV active); m.p.: 179−181 °C; IR (ATR):
D
DOI: 10.1021/acs.joc.7b01639
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
2959, 1785, 1736, 1715, 1646, 1604, 1480, 1397, 1371, 1328, 1288,
1259, 1224, 1182, 1166, 1117 cm−1; 1H (500 MHz, CDCl3) δ 0.91 (t, J
= 7.1 Hz, 3H), 1.19 (s, 3H), 1.24 (s, 3H), 2.33 (d, JAB = 16.4 Hz, 1H),
Hz, 1H), 7.89 (d, J = 8.8 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ
13.7, 27.9 (4C), 28.9, 34.7, 37.5, 50.8, 53.5, 61.7, 85.7, 87.0, 111.5,
116.8, 124.2, 125.6, 130.4, 131.6, 138.7, 148.4, 167.7, 170.8, 176.9,
193.2; HRMS (ESI) calcd for C25H29O7NCl [M + H]+ 490.1627;
found 490.1628.
2.37 (d, JAB = 16.4 Hz, 1H), 2.47 (d, JAB = 18.2 Hz, 1H), 2.51 (d, JAB
=
18.2 Hz, 1H), 2.68 (s, 3H), 3.90 (q, J = 7.1 Hz, 2H), 4.29 (s, 1H), 7.06
(dd, J = 7.5, 2.7 Hz, 1H), 7.14 (ddd, J = 8.9, 8.9, 2.7 Hz, 1H), 8.26 (dd,
J = 9.0, 4.5 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.7, 26.4, 28.1,
28.7, 34.7, 37.5, 50.8, 53.7, 61.7, 87.2, 111.5, 112.8 (d, J = 25.1 Hz,
1C), 118.41 (d, J = 22.4 Hz, 1C), 118.47 (d, J = 7.5 Hz, 1C), 124.6 (d,
J = 8.1 Hz), 136.5, 160.0 (d, J = 245.5 Hz, 1C), 167.4, 169.9, 173.6,
176.8, 193.2; 19F{1H} (470 MHz, CDCl3) δ −115.0; HRMS (ESI)
calcd for C22H23O6NF [M + H]+ 416.1504; found 416.1503.
3m. General Procedure A was followed using 1m (119 mg, 0.3
mmol). The reaction was complete after 1 h at 60 °C, and 3m was
recovered by column chromatography, eluting with 5, 10, 20, and then
30% EtOAc/hexanes, which gave a yellow solid (121 mg) in 76% yield.
Rf = 0.48 (40% EtOAc/hexanes, UV active); m.p.: 125−126 °C; IR
(ATR): 2961, 1781, 1736, 1652, 1605, 1470, 1394, 1370, 1328, 1250,
1
1163, 1147, 1122 cm−1; H (500 MHz, CDCl3) δ 0.94 (t, J = 7.2 Hz,
3i. General Procedure A was followed using 1i (88 mg, 0.3 mmol).
1i did not dissolve in CH3CN, and the reaction proceeded as a
suspension. The reaction was complete after 1 h at 60 °C, and 3i was
observed in 84% NMR yield. An analytically pure sample was
recovered by column chromatography, eluting with 5, 10, 15, 20, and
then 30% EtOAc/hexanes, which gave a white solid that was
characterized. Rf = 0.49 (40% EtOAc/hexanes, UV active); m.p.:
197−199 °C; IR (ATR): 2956, 1782, 1737, 1717, 1646, 1468, 1224,
3H), 1.16 (s, 3H), 1.21 (s, 3H), 1.61 (s, 9H), 2.31 (s, 2H), 2.43 (d, Jab
= 17.7 Hz, 1H), 2.49 (d, Jab = 17.7 Hz, 1H), 3.91 (m, 2H), 4.25 (s,
1H), 7.40 (d, J = 1.9 Hz, 1H), 7.53 (dd, J = 8.8, 2.1 Hz, 1H), 7.82 (d, J
= 8.8 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.7, 27.89 (3C), 27.93,
28.8, 34.7, 37.4, 50.8, 53.4, 61.7, 85.6, 86.8, 111.5, 117.1, 117.7, 124.4,
128.3, 134.5, 139.2, 148.3, 167.6, 170.6, 176.8, 193.1; HRMS (ESI)
calcd for C25H29O7NBr [M + H]+ 534.1122; found 534.1122.
3n. General Procedure A was followed using 1n (87 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3n was recovered by
column chromatography, eluting with 5, 10, 20, and then 30% EtOAc/
hexanes, which gave a yellow/orange oil (129 mg) in 99% yield. Rf =
0.36 (40% EtOAc/hexanes, UV active); IR (ATR): 2959, 1768, 1718,
1646, 1466, 1370, 1338, 1270, 1218, 1168 cm−1; 1H (500 MHz,
CDCl3) δ 1.22 (s, 3H), 1.31 (s, 3H), 2.36 (d, JAB = 16.3 Hz, 1H), 2.43
(d, JAB = 16.3 Hz, 1H), 2.54 (s, 2H), 2.73 (s, 3H), 5.31 (s, 1H), 7.01
(dd, J = 7.6, 7.6 Hz, 1H), 7.16 (dd, J = 6.8, 6.8 Hz, 2H), 7.21 (dd, J =
7.6, 7.6 Hz, 2H), 7.37 (dd, J = 7.4, 7.4 Hz, 1H), 7.46 (d, J = 7.5 Hz,
2H), 7.94 (d, J = 8.3 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 26.5,
28.3, 28.7, 34.7, 37.7, 50.9, 54.2, 87.7, 112.4, 116.4, 122.4, 125.6, 126.4,
127.7 (2C), 128.4 (2C), 131.4, 133.4, 136.3, 139.9, 169.9, 174.4, 176.7,
193.2, 193.9; HRMS (ESI) calcd for C26H24O5N [M + H]+ 430.1649;
found 430.1650.
1
1189, 1174, 1166 cm−1; H (500 MHz, CDCl3) δ 0.92 (t, J = 7.2 Hz,
3H), 1.20 (s, 3H), 1.25 (s, 3H), 2.34 (d, JAB = 16.4 Hz, 1H), 2.38 (d,
JAB = 16.4 Hz, 1H), 2.48 (d, JAB = 18.3 Hz, 1H), 2.52 (d, JAB = 18.3 Hz,
1H), 2.69 (s, 3H), 3.92 (m, 2H), 4.28 (s, 1H), 7.31 (d, J = 2.2 Hz,
1H), 7.42 (dd, J = 8.8, 2.2 Hz, 1H), 8.22 (d, J = 8.8 Hz, 1H); 13C{1H}
(125 MHz, CDCl3) δ 13.7, 26.4, 28.2, 28.8, 34.8, 37.6, 50.9, 53.7, 61.8,
87.1, 111.5, 118.2, 124.6, 125.5, 131.2, 131.8, 139.0, 167.4, 170.0,
173.3, 176.8, 193.2; HRMS (ESI) calcd for C22H23O6NCl [M + H]+
432.1208; found 432.1209.
3j. General Procedure A was followed using 1j (101 mg, 0.3 mmol).
1j did not dissolve in CH3CN, and the reaction proceeded as a
suspension. The reaction was complete after 1 h at 60 °C, and 3c was
observed in 84% NMR yield. An analytically pure sample was
recovered by column chromatography, eluting with 5, 10, 15, 20, and
then 30% EtOAc/hexanes, which gave a white solid that was
characterized. Rf = 0.48 (40% EtOAc/hexanes, UV active); m.p.:
198−200 °C; IR (ATR): 2954, 1787, 1737, 1717, 1646, 1466, 1372,
1315, 1254, 1224, 1188, 1166 cm−1; 1H (500 MHz, CDCl3) δ 0.94 (t, J
= 7.1 Hz, 3H), 1.20 (s, 3H), 1.25 (s, 3H), 2.34 (d, JAB = 16.4 Hz, 1H),
2.38 (d, JAB = 16.4 Hz, 1H), 2.50 (s, 2H), 2.68 (s, 3H), 3.83 (m, 2H),
4.28 (s, 1H), 7.45 (s, 1H), 7.57 (d, J = 8.7 Hz, 1H), 8.17 (d, J = 8.8
Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.7, 26.5, 28.1, 28.7, 34.7,
37.5, 50.9, 53.7, 61.8, 87.0, 111.5, 118.50, 118.60, 124.8, 128.3, 134.7,
139.5, 167.4, 170.0, 173.2, 176.8, 193.2; HRMS (ESI) calcd for
C22H23O6NBr [M + H]+ 476.0703; found 476.0705.
3o. General Procedure A was followed using 1o (69 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3o was recovered as
a yellow/orange solid (98 mg) in 89% yield. Rf = 0.34 (40% EtOAc/
hexanes, UV active); m.p.: 193−194 °C; IR (ATR): 2962, 2932, 1777,
1713, 1645, 1606, 1468 1395, 1367, 1340, 1272, 1220, 1177 cm−1; 1H
(500 MHz, CDCl3) δ 1.19 (s, 3H), 1.24 (s, 3H), 1.81 (s, 3H), 2.33 (s,
2H), 2.50 (s, 2H), 2.69 (s, 3H), 4.37 (s, 1H), 7.20 (d, J = 4.1 Hz, 2H),
7.44 (m, 1H), 8.26 (d, J = 8.2 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ
26.6, 28.3, 28.7, 31.4, 34.7, 37.5, 50.7, 58.5, 87.5, 112.6, 116.9, 121.9,
125.9, 126.2, 131.9, 140.3, 170.2, 174.0, 177.2, 193.5, 202.8; HRMS
(ESI) calcd for C21H22O5N [M + H]+ 368.1493; found 368.1492.
3p. General Procedure A was followed using 1p (79 mg, 0.3 mmol).
The reaction was complete after 15 h at 60 °C, and 3p was recovered
by column chromatography, eluting with 5, 10, 15, 20, and then 30%
EtOAc/hexanes, which gave a pale yellow solid (99 mg) in 82% yield.
Rf = 0.44 (40% EtOAc/hexanes, UV active); m.p.: 164−166 °C; IR
3k. General Procedure A was followed using 1k (101 mg, 0.3
mmol). The reaction was complete after 1 h at 60 °C, and 3k was
recovered by column chromatography, eluting with 5, 10, 20, and then
30% EtOAc/hexanes, which gave a white solid (104 mg) in 73% yield.
Rf = 0.48 (40% EtOAc/hexanes, UV active); m.p.: 161−162 °C; IR
1
(ATR): 2965, 1784, 1728, 1652, 1486, 1162, 1144, 1116 cm−1; H
1
(ATR): 2961, 1763, 1717, 1607, 1466, 1265, 1171 cm−1; H (500
(500 MHz, CDCl3) δ 0.93 (t, J = 7.2 Hz, 3H), 1.17 (s, 3H), 1.22 (s,
3H), 1.62 (s, 9H), 2.32 (s, 2H), 2.44 (d, JAB = 17.7 Hz, 1H), 2.50 (d,
JAB = 17.7 Hz, 1H), 3.91 (q, J = 7.2 Hz, 2H), 4.29 (s, 1H), 7.04 (dd, J
= 7.5, 2.7 Hz, 1H), 7.12 (ddd, J = 8.9, 8.9, 2.7 Hz, 1H), 7.92 (dd, J =
9.0, 4.4 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.7, 27.9, 28.9 (4C),
34.7, 37.5, 50.8, 53.4, 61.6, 85.5, 87.1, 111.5, 113.0 (d, J = 25.0 Hz),
116.9 (d, J = 7.6 Hz), 118.3 (d, J = 22.6 Hz), 124.1 (d, J = 8.3 Hz),
136.2 (d, J = 2.4 Hz), 148.5, 159.7 (d, J = 244.5 Hz), 167.7, 171.1,
176.9, 193.1; 19F{1H} (470 MHz, CDCl3) δ −115.0; HRMS (ESI)
calcd for C25H29O7NF [M + H]+ 474.1923; found 474.1923.
3l. General Procedure A was followed using 1l (106 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3l was recovered by
column chromatography, eluting with 5, 10, 20, and then 30% EtOAc/
hexanes, which gave a pale yellow solid (113 mg) in 77% yield. Rf =
0.50 (40% EtOAc/hexanes, UV active); m.p.: 139−141 °C; IR (ATR):
2961, 1781, 1736, 1653, 1470, 1328, 1250, 1148, 1120 cm−1; 1H (500
MHz, CDCl3) δ 0.94 (t, J = 7.1 Hz, 3H), 1.18 (s, 3H), 1.23 (s, 3H),
MHz, CDCl3) δ 1.27 (s, 3H), 1.33 (s, 3H), 2.42 (s, 2H), 2.59 (d, JAB
=
18.9 Hz, 1H), 2.63 (d, JAB = 18.9 Hz, 1H), 2.72 (s, 3H), 4.69 (s, 1H),
6.39 (d, J = 7.6 Hz, 1H), 6.77 (dd, J = 7.5, 7.5 Hz, 1H), 6.83 (s, 2H),
7.14 (s, 3H), 7.22 (dd, J = 8.2, 8.2 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H);
13C{1H} (125 MHz, CDCl3) δ 26.6, 28.6, 29.1, 34.3, 37.9, 51.4, 53.3,
90.7, 113.7, 116.3, 122.9, 124.8, 126.2, 127.8, 128.3 (2C), 128.4 (2C),
130.7, 135.8, 140.1, 170.4, 175.2, 177.0, 193.6; HRMS (ESI) calcd for
C25H24O4N [M + H]+ 402.1700; found 402.1700.
3q. General Procedure A was followed using 1a (78 mg, 0.3 mmol).
The reaction was complete after 1 h at 60 °C, and 3q was recovered as
a white solid (108 mg) in 97% yield. Rf = 0.23 (40% EtOAc/hexanes,
UV active); m.p.: 142−143 °C; IR (ATR): 2998, 2952, 1775, 1733,
1709, 1648, 1603, 1171 cm−1; 1H (500 MHz, CDCl3) δ 0.80 (t, J = 7.2
Hz, 3H), 2.21 (m, 2H), 2.49 (m, 2H), 2.65 (m, 2H), 2.71 (s, 3H), 3.81
(m, 2H), 4.34 (s, 1H), 7.21 (dd, J = 7.6, 7.6 Hz, 1H), 7.35 (d, J = 7.0
Hz, 1H), 7.45 (ddd, J = 7.9, 7.9, 1.4 Hz, 1H), 8.26 (d, J = 8.3 Hz, 1H);
13C{1H} (125 MHz, CDCl3) δ 13.5, 21.5, 23.8, 26.5, 36.4, 53.8, 61.4,
87.4, 112.6, 116.8, 123.0, 125.3, 125.6, 131.8, 140.5, 167.4, 170.1,
1.62 (s, 9H), 2.33 (s, 2H), 2.44 (d, JAB = 17.8 Hz, 1H), 2.50 (d, JAB
=
17.8 Hz, 1H), 3.93 (m, 2H), 4.28 (s, 1H), 7.29 (s, 1H), 7.39 (d, J = 8.7
E
DOI: 10.1021/acs.joc.7b01639
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
174.1, 177.7, 193.7; HRMS (ESI) calcd for C20H20O6N [M + H]+
370.1285; found 370.1284.
(4) (a) Zhu, C.; Yoshimura, A.; Ji, L.; Wei, Y.; Nemykin, V. N.;
Zhdankin, V. V. Org. Lett. 2012, 14, 3170. (b) Muller, P.; Allenbach,
̈
3s. General Procedure A was followed using 1a (52 mg, 0.2 mmol).
The reaction was complete after 22 h at 60 °C, and 3s was recovered
by column chromatography, eluting with 5, 10, 20, and then 30%
EtOAc/hexanes, which gave a white solid (45 mg) in 54% yield. Rf =
0.43 (40% EtOAc/hexanes, UV active); m.p.: 186−188 °C; IR (ATR):
2979, 1770, 1744, 1723, 1661, 1607, 1371, 1276, 1165 cm−1; 1H (500
MHz, CDCl3) δ 0.85 (t, J = 7.1 Hz, 3H), 2.75 (s, 3H), 2.89 (m, 2H),
4.68 (s, 1H), 7.24 (dd, J = 7.6, 7.6 Hz, 1H), 7.32 (dd, J = 7.5, 7.5 Hz,
1H), 7.39 (d, J = 7.7 Hz, 1H), 7.46 (d, J = 8.5 Hz, 1H), 7.51 (dd, J =
7.6, 7.6 Hz, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.65 (dd, J = 7.6, 7.6 Hz,
1H), 8.32 (d, J = 8.3 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.6,
26.6, 54.2, 62.0, 89.0, 101.1, 111.7, 117.1, 117.3, 122.5, 123.2, 124.3,
125.5, 125.9, 132.4, 133.6, 140.8, 155.5, 158.8, 166.5, 167.2, 170.1,
173.5; HRMS (ESI) calcd for C23H18O7N [M + H]+ 420.1078; found
420.1077.
3t. General Procedure A was followed using 1a (52 mg, 0.2 mmol).
The reaction was complete after 11 h at 60 °C, and 3t was recovered
by column chromatography, eluting with 10, 20, 30, 40, and then 50%
EtOAc/hexanes, which gave a purple solid (37 mg) in 45% yield. Rf =
0.19 (40% EtOAc/hexanes, UV active); m.p.: 182−184 °C; IR (ATR):
2960, 1772, 1738, 1710, 1678, 1658, 1509, 1465, 1176. cm−1; 1H (500
MHz, CDCl3) δ 0.82 (t, J = 7.1 Hz, 3H), 2.72 (s, 3H), 3.35 (s, 3H),
3.36 (s, 3H), 3.79 (m, 1H), 3.88 (m, 1H), 4.50 (s, 1H), 7.25 (dd, J =
7.6, 7.6 Hz, 1H), 7.40 (d, J = 7.7 Hz, 1H), 7.50 (dd, J = 7.8, 7.8 Hz,
1H), 8.29 (d, J = 8.3 Hz, 1H); 13C{1H} (125 MHz, CDCl3) δ 13.6,
26.5, 28.2, 29.9, 53.3, 61.9, 85.8, 88.0, 117.1, 121.6, 125.4, 125.8, 132.5,
140.7, 151.2, 158.9, 162.2, 167.2, 170.0, 172.9 ; HRMS (ESI) calcd for
C20H20O7N3 [M + H]+ 414.1296; found 414.1297.
Y.; Robert, E. Tetrahedron: Asymmetry 2003, 14, 779. (c) Muller, P.;
̈
Fernandez, D.; Nury, P.; Rossier, J.-C. J. Phys. Org. Chem. 1998, 11,
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Hadjiarapoglou, L. P. J. Org. Chem. 2015, 80, 1279.
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N.; Zhdankin, V. V. Chem. Commun. 2012, 48, 10108.
(10) (a) Goudou, F.; Petit, P.; Moriou, C.; Gros, O.; Al-Mourabit, A.
J. Nat. Prod. 2017, 80, 1693. (b) Zhou, M.; Miao, M.-M.; Du, G.; Li,
X.-N.; Shang, S.-Z.; Zhao, W.; Liu, Z.-H.; Yang, G.-Y.; Che, C.-T.; Hu,
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69, 5631.
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Chem. 2006, 71, 2346. (b) Alcaide, B.; Almendros, P.; Rodríguez-
Acebes, R. Chem. - Eur. J. 2005, 11, 5708. (c) Roh, H. J.; Kim, S. Y.;
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2017, 53, 6860.
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T. Tetrahedron Lett. 2007, 48, 2943. (b) Basavaiah, D.; Badsara, S. S.;
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2011, 353, 1961.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.7b01639.
Reaction optimization and control experiment tables,
NMR spectra used for elucidation of 3a, and spectra of
all new compounds (PDF)
(16) (a) Ho, P. E.; Tao, J.; Murphy, G. K. Eur. J. Org. Chem. 2013,
2013, 6540. (b) Tao, J.; Tuck, T. N.; Murphy, G. K. Synthesis 2016, 48,
772.
(17) Tao, J.; Estrada, C. D.; Murphy, G. K. Chem. Commun. 2017,
DOI: 10.1039/C7CC04859A.
Crystallographic data for 3a (CIF)
(18) (a) Hayasi, Y.; Okada, T.; Kawanisi, M. Bull. Chem. Soc. Jpn.
1970, 43, 2506. (b) Tu, X.-C.; Yu, Y.; Tu, M.-S.; Jiang, B.; Li, C.; Tu,
S.-J. J. Heterocycl. Chem. 2014, 51, 436.
(19) Guo, J.; Liu, Y.; Li, X.; Liu, X.; Lin, L.; Feng, X. Chem. Sci. 2016,
7, 2717.
AUTHOR INFORMATION
Corresponding Author
*E-mail: graham.murphy@uwaterloo.ca.
ORCID
■
(20) The structure of 3a is consistent with most literature precedents.
However, the opposite regioisomer has been observed with α,β-
unsaturated compounds; see: Yong, R. L.; Yoon, S. H.; Seo, Y.; Kim, B.
S. Synthesis 2004, 2004, 2787.
Graham K. Murphy: 0000-0002-8795-2404
Notes
The authors declare no competing financial interest.
(21) (a) Kalpogiannaki, D.; Martini, C.-I.; Nikopoulou, A.; Nyxas, J.
A.; Pantazi, V.; Hadjiarapoglou, L. P. Tetrahedron 2013, 69, 1566.
(b) Karade, N. N.; Shirodkar, S. G.; Patil, M. N.; Potrekar, R. A.;
Karade, H. N. Tetrahedron Lett. 2003, 44, 6729.
(22) (a) Alexiou, I.; Gogonas, E. P.; Hadjiarapoglou, L. P. Synlett
1999, 1999, 1925. (b) Bosnidou, A. E.; Kalpogiannaki, D.;
Karanestora, S.; Nixas, J. A.; Hadjiarapoglou, L. P. J. Org. Chem.
2015, 80, 1279.
(23) This mechanism fails to explain why N-EWG substrates react
faster than N-alkyl substrates. This discrepancy might be better
explained by a radical reaction proceeding through a stabilized
captodative radical.
(24) Liu, Y.-Y.; Duan, S.-W.; Zhang, R.; Liu, Y.-H.; Chen, J.-R.; Xiao,
W.-J. Org. Biomol. Chem. 2016, 14, 5224.
ACKNOWLEDGMENTS
■
This work was supported by the Natural Sciences and
Engineering Research Council (NSERC) of Canada and the
University of Waterloo. J.T. was supported by a NSERC PGS-
D and an Ontario Graduate Scholarship. B.L. is supported by
an NSERC USRA. We acknowledge Dr. Assoud for conducting
the X-ray analysis.
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DOI: 10.1021/acs.joc.7b01639
J. Org. Chem. XXXX, XXX, XXX−XXX