Aminolactonization of Unactivated Alkenes Catalyzed by Aryl Iodine

Article abstract of DOI:10.1021/acs.joc.1c00074

A one-step protocol of the aryl iodine-catalyzed aminolactonization of unactivated alkenes under oxidation conditions was first reported to efficiently construct diverse amino lactones in a short time using HNTs2 as the compatible nitrogen source. In addi

Full text of DOI:10.1021/acs.joc.1c00074

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Aminolactonization of Unactivated Alkenes Catalyzed by Aryl Iodine
Lu-Wen Zhang, Xiao-Jun Deng, Dong-Xu Zhang, Qin-Qin Tian, and Wei He*
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ABSTRACT: A one-step protocol of the aryl iodine-catalyzed
aminolactonization of unactivated alkenes under oxidation
conditions was first reported to efficiently construct diverse
amino lactones in a short time using HNTs2 as the compatible
nitrogen source. In addition, we investigated the influence of the
reaction rate based on the structure of the iodoarene precatalyst,
which revealed the selective adjustment effect on aminolactoniza-
tion and oxylactonization. Finally, preliminary experiments verified
the feasibility of asymmetric aminolactonization catalyzed by a
chiral iodoarene precatalyst.
Scheme 1. Related Works
INTRODUCTION
■
The oxyamination of alkenes1 is a recently developed synthesis
strategy used to simultaneously construct C−O bonds and C−
N bonds, and transition metals, such as Cu,2 Pd,3 Fe,4 Os,5 Ir,6
Rh,7 Mn,8 etc.,9 are widely applied in these reactions. The
direct aminoxygenation of alkenes can yield privileged amino
lactones, which are prevalent motifs in diverse natural and
synthetic biologically active compounds,10 and they can be
converted to other skeletons,11 such as 1,2-amino alcohol and
tetrahydrofuran derivatives. At present, the majority of reports
on the aminolactonization of alkenes involve catalysis by the
transition metal copper12 (Scheme 1a). Usually, several
strategies require olefin substrates containing backbones to
favor cyclization via radical processes.12c−e Some copper-
catalyzed methods need pre-synthesis of nitrogen reagents that
are relatively unstable.12a,b,d In addition, due to the require-
ments of the backbone in the substrates, the product range is
always inflexible.12b,c Therefore, there are still opportunities to
develop novel and facile methods to realize the amino-
lactonization with mild conditions.
Iodine(I/III) has low toxicity and mild properties and is
regarded as a “green substitute” for transition metals in organic
synthesis.13 Iodoarene is an efficient and atom-economic
catalyst that can generate hypervalent iodine in situ under
oxidative conditions and catalyze the difunctionalization14 of
alkenes for the construction of C−X bonds.15−21 At present,
general catalytic strategies based on aryl iodine(I/III) can
realize the halolactonization,22 oxylactonization,23 and other
transformations24 of alkenes (Scheme 1b). However, up to
now, to the best of our knowledge, the aminolactonization of
unactivated alkenes catalyzed by aryl iodine (I/III) has seldom
been reported. We think that there are two main challenges in
realizing the aryl iodine(I)/oxidant-catalyzed amino lactoniza-
tion of unactivated alkenes: (1) nitrogen reagents must be
compatible with oxidants/substrates and can generate ArI[N]2
species in situ,15e and (2) the background dioxidation reaction
should be avoided to reduce the formation of byproducts.25
Recently, some literature reports15a−d have used equivalents of
ArI[N(SO2R)2]2 or a catalytic amount of ArI/HN(SO2R)2 to
Received: January 11, 2021
Published: March 24, 2021
https://doi.org/10.1021/acs.joc.1c00074
© 2021 American Chemical Society
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achieve the diamination of olefins and suggested15c that the
PhI(NTs2)2 species tends to dissociate in solution, releasing
[PhINTs2]+ with catalytic activity, and a large amount of
excellent nitrogen nucleophile [NTs2]−, which can effectively
construct C−N bonds (Scheme 1c). Therefore, using HN-
(SO2R)2 as a compatible nitrogen reagent may realize the aryl
iodine-catalyzed aminolactonization of unactivated alkenes. In
our previous work,26 iodoarene-catalyzed oxyamination of
alkenes was successfully performed to synthesize 5-imino-2-
tetrahydrofuranyl methanamine derivatives using HN(SO2R)2,
but the product needed to be further hydrolyzed to obtain
amino lactones. On the above basis, herein, we used more
easily available unactivated alkenyl acids as substrates and
developed a one-step aryl iodine/oxidant catalyst system to
construct diverse amino lactones.
focused our attention on the screening of nitrogen reagents
and found that, among all the tested nitrogen sources, N1−N4
could be used as compatible nitrogen reagents with yields of
75−95% (Table 1, nitrogen source), and HNTs2 was the best
nitrogen reagent. Subsequently, a detailed screening of the type
and amount of oxidant was carried out (see the Supporting
Information (SI)), and ultimately, we chose 1.75 equiv of
mCPBA as the matching oxidant (Table 1, entry 10). Then,
the amount of catalyst was screened (Table 1, entries 10−12),
showing that 0.1 equiv of I11 had better performance. In
addition, KI and I2 were investigated under the same
conditions (Table 1, entries 13 and 14). Compared with KI,
I2 has better solubility in CH3CN and better catalytic result,
but both results were disappointing.
We also screened the type (see the SI) of catalysts, and the
results indicated that the structure of the iodoarene precatalyst
1
RESULTS AND DISCUSSION
largely affected the catalytic activity. Therefore, H NMR was
■
used to monitor the conversion of 1e to 2e catalyzed by six
precatalysts with different structures, and the initial reaction
rates were calculated based on the change in substrate
concentration−time (Table 2). Taking I11 and I7 as examples,
the structure on the aryl iodophenyl group affected the target
product conversion rate, and the reaction rate of I11 was
higher than that of I7, while I11 effectively reduced the extent
In the initial investigation, HNTs2 was used as the nitrogen
reagent, and iodoarene I11 was used as the precatalyst to
catalyze the aminolactonization of 2,2-diphenylpent-4-enoic
acid 1e in HFIP to obtain 5-amino-γ-butyrolactone 2e with a
yield of 44% (Table 1, entry 1). Therefore, we used 1e as the
model substrate for condition screening. First, a series of
solvents were screened to improve the reaction result (Table 1,
entries 2−9), and the yield of 2e was improved to 95% when
the reaction proceeded in CH3CN (Table 1, entry 9). Next, we
Table 2. Reaction Rates for the Conversion of 4-Pentenoic
Acid, 1e, to 2e with Iodoarene Precatalysts I1−I2, I7, I11−
1
I13, Detected by H NMR Analysis
Table 1. Reaction Optimizations
a
b
entry
cat. (Y mol %)
oxidant (X equiv)
solvent
yield (%)
44
1
2
3
4
5
6
7
8
9
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (15)
I11 (10)
I11 (5)
KI
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (1.75)
mCPBA (1.75)
mCPBA (1.75)
mCPBA (1.75)
mCPBA (1.75)
HFIP
THF
EtOH
MeOH
TFE
5
20
74
63
85
82
95
DCM
DCE
CF3-Ph
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
d
e
10
98
98
d
e
11
a
b
b
c
entry
ArI
time
2e yield (%)
2e′ yield (%)
K
d
e
12
f
50
1
2
3
4
5
6
I1
I2
I7
I11
I12
I13
12.5
10.5
7.5
2.5
4.0
50
75
80
98
90
8
17
25
20
ND
8
1.68 × 10−6
2.63 × 10−6
3.62 × 10−6
1.19 × 10−5
6.15 × 10−6
1.44 × 10−6
13
10
56
g
14
I2
d
a
General conditions: 1e (0.2 mmol), HNTs2 (1.5 equiv), I11 (15 mol
%), mCPBA (X equiv), solvent (2 mL), r.t., 2−12 h, air atmosphere.
b
c
10.5
44
Isolated yield. 1e (0.2 mmol), nitrogen reagent (1.5 equiv), I11 (15
mol %), mCPBA (2.0 equiv), CH3CN (2 mL), r.t., 2.5−5 h, air
d
a
atmosphere. 1e (0.05 mmol), HNTs2 (1.5 equiv), I11 (Y mol %),
General conditions: 1e (0.05 mmol), HNTs2 (1.5 equiv), ArI (10
b
e
mCPBA (1.75 equiv), CD3CN (0.5 mL), r.t. Detected by NMR and
mol %), mCPBA (1.75 equiv), CD3CN (0.5 mL), r.t. Detected by
f
c
1,2-dibromomethane as the internal standard. KI (1.0 equiv) instead
NMR and 1,2-dibromomethane as the internal standard. K mol/L·
g
d
of I11. I2 (1.0 equiv) instead of I11.
S−1. Not detected.
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of dioxygenation, which differs from the results presented in
the literature.27 However, the presence of the more electron-
donating o-isopropoxy groups in I12 had a detrimental effect
on this transformation. The precatalyst I13 with a strong
electron-withdrawing substitution group (−NO2), which
affected the transformation of amino lactone, led to the
formation of byproduct 2e′ with a 44% yield. These results
indicated that a catalyst with a higher initial reaction rate will
affect the reaction time, which effectively reduced the extent of
dioxygenation and increased the yield of the target product.
Essentially, the electronics of the precatalyst can adjust the
selectivity of this transformation due to the oxidation rate of
iodoarenes by mCPBA and the dissociation rate of ArI(NTs2)2
to generate [ArINTs2]+ and [NTs2]−.
nPr, Ph, Bn, and 4-OMe-Ph) worked well in all cases,
furnishing the desired products in 65−95% yields (2b−2g).
3,3-Dimethyl 4-pentenoic acid, 1h, showed slightly worse
reactivity, obtaining 2h with a 50% yield, which indicated that
3-substitution on the substrate had a weak effect on the
reaction. Moreover, 2i and 2j were generated in moderate
isolated yields and contained a sterically congested carbon
center at C4. The yield of internal olefin substrate 1k was 50%
under standard conditions with a high diastereomer ratio. A
diverse series of 2-cyclo-4-pentenoic acids containing carbon
and heterocyclic motifs, 1l−1q, were converted to spirocyclic
lactone structures with good efficiencies. Interestingly, 2,2-
diallylmalonic acid, 1r, was converted to 2,7-dioxaspiro[4.4]-
nonane-1,6-dione, 2r, with double the equivalents of the
reagents to prove the practicability of this method. In addition,
the product of 2s was generated with a 42% yield by the
cyclization/amination of carbonyl acid (without the partic-
ipation of carbonyl ester), showing that the activity of the
carboxylic acid is higher than that of the ester in this reaction
system.
With the optimal conditions in hand, we then examined the
scope of alkenyl acids substrates (Scheme 2). First, 4-
pentenoic acid was submitted to catalytic conditions, and 2a
was obtained in a 75% yield. In general, 2,2-disubstituted 4-
pentenoic acids containing different steric bulk groups (Me, Et,
Then, we explored the scope of mono- and multiple-
substituted unactivated alkenes. First, a range of 3-substituted
lactones were constructed, which furnished good yields (2aa−
2af). The steric bulk of the 3-position substituent will
dramatically affect the diastereomer ratios of the products.
When substituted −R3 was a methyl group, the diastereomer
ratio was only 2.8:1 (2ag), whereas, when it was an ethyl group
(2ah) or n-propyl group (2ai), excellent diastereoselectivities
were observed. The substrates of 1aj and 1ak also produced
good yields. Substrate 1al had greater steric hindrance than
1ak, but its diastereomeric ratio was not satisfactory. Finally, a
product containing three chiral centers, 2am, was obtained
with a moderate yield. The structures of 2b, 2d, 2k, 2m, 2o,
2ah, and 2ai were determined via X-ray crystallographic
analysis (see the SI).
a b
,
Scheme 2. Substrate Scope 1
Under standard conditions, the aromatic substrate 3a was
converted to product 4a with a low yield of 18% and poor
selectivity. We further optimized the reaction conditions, and a
series of aromatic substrates were smoothly converted to 5-exo
products12e (Scheme 3), furnishing the amino lactones with
moderate yields and excellent selectivities. In this trans-
formation, the solvent effect was apparent, and when HFIP was
used instead of CH3CN as the reaction solvent, 4a−4c and 4g
were regioselectively obtained. 3f, with a methyl group
tethered with olefin, could be converted to 5-exo products in
CH3CN. Unfortunately, para-NO2-substituted acid 3d was not
a b
,
Scheme 3. Substrate Scope 2
a
General conditions: 1 (0.2 mmol), HNTs2 (1.5 equiv), I11 (10 mol
%), mCPBA (1.75 equiv), CH3CN (2 mL), r.t., 2.5−5 h, air
b
c
atmosphere. Isolated yield. Diastereomeric ratio determined by
d
a
NMR. Detected by NMR and 1,2-dibromomethane as the internal
standard. 1 (0.2 mmol), HNTs2 (3.0 equiv), I11 (20 mol %),
mCPBA (2.5 equiv), CH3CN (4 mL), r.t., 5 h, air atmosphere. The
General conditions: 3 (0.2 mmol), I11 (15 mol %), mCPBA (1.75
equiv), HNTs2 (1.5 equiv), HFIP(3 mL), r.t. 5−12 h, air atmosphere.
e
f
b
c
d
e
Isolated yield. I1 as catalyst. CH3CN as solvent. Detected by
structure determined via X-ray.
NMR and 1,2-dibromomethane as the internal standard.
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converted to a product in either HFIP or CH3CN. The simple
iodobenzene I1 catalyst can convert 3e to 4e with high
regioselectivity, but I11 was very poor for this substrate.
Control experiments were conducted to investigate the
reaction process. First, the catalyst was explored. Substrate 1e
was converted into 2e within 2.5 h, resulting in a yield of 95%
via method A, which was more atom economical and practical
than methods B and C (Scheme 4a). The strategy of generated
On the basis of the current results,14a,23d a plausible reaction
pathway of this iodoarene-catalyzed aminolactonization
reaction is shown in Scheme 5. The reaction was initiated by
Scheme 5. Plausible Reaction Mechanism
Scheme 4. Control Experiments
the mCPBA oxidation of precatalyst I11 in the presence of
HNTs2 to generate aryl-λ3-iodane in situ. Next, aryl-λ3-iodane
can dissociate15c into [ArINTs2]+ and [NTs2]−, and then,
substrate 1e could undergo electrophilic addition with
[ArINTs2]+, converting to iodonium intermediate A. Further,
intermediate B was achieved by the intramolecular nucleo-
philic cyclization of intermediate A. [NTs2]− was removed, and
cationic intermediate C underwent nucleophilic addition to
produce target product 2e. Meanwhile, precatalyst I11 was
released, which finished the catalytic cycle. On the basis of
previous studies,25 oxylactonization byproduct generation
proceeds via oxidation of substrate alkene 1e by an in situ
generation epoxide intermediate D when using mCPBA as the
oxidant. Subsequently, epoxide intermediate D was attacked by
carbonyl groups and cyclized to produce oxylactone by-
products.
To prove the synthetic utility and versatility of this reaction,
a gram-scale reaction was achieved, and desired product 2q
was obtained in a 70% yield (Scheme 6). Notably, 48% of
precatalyst I11 was recovered and reused for the reaction,
giving the same reaction result. Next, amino lactone 2q was
transformed into 1,5-dihydroxyamine 5 in a 85% yield using
BH3·THF for carbon reduction. Furthermore, 2q can be
hypervalent iodine in situ is a more atom economical catalytic
method and was also applicable in our reactions. The
prepreparation15c process of PhI(NTs2)2 was complicated,
and an excessive dose was needed. Second, the difference in
the activities of carboxylic acid and the corresponding ester was
further confirmed. When ester substrate 1t was tested, the
same product, 2e, was observed but with a lower yield (50% vs
95%) under the same conditions (Scheme 4b). These results
were consistent with those of the previous substrate 1s,
illustrating that unsaturated carboxylic acids were more
compatible with these amino oxygenation conditions than
ester substrates. Third, to investigate the mechanism of this
process, several control experiments were conducted (Scheme
4c,d). The absence of an iodoarene precatalyst resulted in
complete inhibition of aminolactonization, while, in the
presence of mCPBA, dioxygenation product 2e′ was observed,
which was formed by the main side reaction. However, with
mCPBA and HNTs2, a 10% yield of 2e′ was produced and 1e
still has 90% remaining, which was in sharp contrast with the
result obtained for the condition where only mCPBA was used
(Scheme 4c). Moreover, 2e cannot be produced from
byproduct 2e′ by directly using PhI(NTs2)2 or HNTs2
(Scheme 4d). This result indicated that the mechanism of
the byproduct is epoxidation/dioxidation mediated by
mCPBA, which is different from that of the target product
catalyzed by iodoarene.
a
Scheme 6. Further Transformations
a
General conditions: a: BH3·THF, 1 h, r.t. b: HBr (33 wt % in acetic
acid), resorcinol, 85 °C, 24 h. c: CH3CH2I, K2CO3, THF, 69 °C, 24 h.
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converted to tricyclic antidepressant analogue 710b by simple
deprotection and alkylation processes. These derivatives
showcased the synthetic value of this method and could
provide numerous nitrogen-containing heterocyclic com-
pounds, which may serve as potential pharmaceutical
precursors.
Finally, to achieve the asymmetric aminolactonization of
alkenyl acids, preliminary studies were conducted with chiral
aryl iodine catalyst 1 (Scheme 7). Model substrate 1e can
purification. Reaction progress was monitored by thin layer
chromatography (0.15−0.2 mm thickness) with visualization by
exposure to a 254 nm UV lamp or molecule iodine, and TLC
purchased from Rushan Taiyang Company of China. Flash column
chromatography was performed on the glass column filled in 200−
300 mesh silica gel (silica gel purchased from Yantai Company of
China) and eluted with petroleum ether/EtOAc or dichloromethane/
1
methanol. All H NMR, 13C {1H} NMR spectra were recorded on
Bruker AV-400 or AV-600. Chemical shifts were reported relative to
1
internal tetramethylsilane (δ 0.00 ppm), CDCl3 (δ 7.26 ppm) for H
and CDCl3 (δ 77.16 ppm) for 13C {1H}, (CD3)2SO (δ 2.50 ppm) for
1H and (CD3)2SO (δ 39.52 ppm) for 13C {1H}, CD3OD (δ 3.31
ppm) for 1H and CD3OD (δ 49.00 ppm) for 13C {1H}, CD3CN (δ =
1.94 ppm) for 1H. Multiplicity was indicated as follows: s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of
doublet), dt (doublet of triplets), dq (doublet of quartets), td (triplet
of doublets), ddd (doublet of doublet of doublets). Coupling
constants were reported in hertz (Hz). HRMS were performed on a
Waters I-Class VION IMS Q-TOF Mass Spectrometer or a Bruker
ESI-Q-TOF (maxis) Mass Spectrometer. Enantiomeric excess (ee)
determination was carried out on an Agilent 1260 interfaced to a HP
71 series computer workstation with Chiralpak IA3/OD-H column.
Melting points were determined by a microscopic melting point tester
(X-6). IR spectra were recorded as KBr disks (Shimadzu FTIR-
8400S). X-ray single-crystal diffraction data were collected on a
Bruker APEX-II CCD diffractometer
a b c
, ,
Scheme 7. Asymmetric Transformation
General Procedures for Preparation of Substrates. All the
substrates 1 and 3 were synthesized according to reported
procedures.28 1ah−1ai and 1al are new compounds characterized
by NMR, HRMS (ESI), and IR.
2,2-Diphenylhex-4-enoic Acid (1k). Synthesized from 2,2-
diphenylacetic acid according to the literature.28e Purified by silica
gel column chromatography (the eluent was petroleum ether/EtOAc
10:1) as a white solid (2.1 g, 80%). H NMR (400 MHz, CDCl3) δ
7.34−7.29 (m, 10H), 5.28 (ddt, J = 16.8, 12.0, 6.0 Hz, 2H), 3.10 (d, J
= 6.0 Hz, 2H), 1.51 (d, J = 5.6 Hz, 3H).
a
1
General conditions: 1 (0.1 mmol), HNTs2 (1.5 equiv), ArI*1 (15
mol %), mCPBA (1.75 equiv), benzotrifluoride (1 mL), −10 °C, 60 h.
b
c
Isolated yield. Enantiomeric excess determined by chiral HPLC
analysis.
3-Ethyl-2,2-diphenylpent-4-enoic Acid (1ah). Synthesized from
2,2-diphenylacetic acid according to the literature.28e Purified by silica
gel column chromatography (the eluent was petroleum ether/EtOAc
obtain an 88% enantiomeric excess and an 89% yield.
However, a series of substrates obtained less enantiomeric
excess (2b*, 2d*, 2n*) for initial substrate expansion. Through
analysis, the catalytic system was highly dependent on the
substrate structure of the 2,2-diphenyl substituent.26 It is
necessary to further adjust the structure of the catalyst and
optimize the reaction conditions, and further research is still
being carried out in our laboratory.
1
10:1) as a white solid (1.4 g, 41%). mp 186.3−187.0 °C. H NMR
(400 MHz, CDCl3): δ 7.35−7.22 (m, 10H), 5.34−5.08 (m, 3H), 3.42
(t, J = 9.2 Hz, 1H), 1.72−1.60 (m, 1H), 0.87 (t, J = 7.2 Hz, 3H),
0.65−0.48 (m, 1H). 13C {1H} NMR (100 MHz, CDCl3): δ 179.6,
140.2, 139.6, 137.6, 131.0, 130.2, 127.7, 127.1, 127.1, 126.9, 119.0,
64.9, 48.8, 23.6, 12.1. IRνmax (cm−1): 3075, 2975, 2875, 2625, 1700,
1680, 1665, 1600, 1497, 1450, 1260, 922, 713, 663. HRMS (ESI) m/
z: [M + Na]+ Calcd for C19H20NaO2 303.1356; found 303.1352.
2,2-Diphenyl-3-vinylhexanoic Acid (1ai). Synthesized from 2,2-
diphenylacetic acid according to the literature.28e Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc
CONCLUSION
■
In conclusion, the aryl iodine/oxidant system was first applied
in the aminolactonization of unactivated alkenes. This protocol
was compatible with mono-substituted, multiple-substituted,
and benzoyl-alkenes to produce diverse amino lactones.
Through control experiments and calculations of the reaction
rate, a reasonable reaction mechanism was proposed. More-
over, a tricyclic antidepressant analogue was synthesized
through this transformation, which confirmed the potential
value for synthetic applications in pharmacophoric and
medicinal research. In addition, this work also provided a
basis for the exploration of rare asymmetric aminolactoniza-
tions by using a new chiral aryl iodine reagent, and further
research is being carried out in our laboratory.
1
10:1) as a white solid (2.4 g, 68%). mp 152.5−153.3 °C. H NMR
(400 MHz, CDCl3): δ 7.38−7.25 (m, 10H), 5.36−5.08 (m, 3H), 3.58
(t, J = 9.6 Hz, 1H), 1.64−1.51 (m, 1H), 1.44−1.32 (m, 1H), 1.27 (dt,
J = 14.8, 8.0 Hz, 1H), 0.87 (t, J = 7.2 Hz, 3H), 0.59 (q, J = 9.6 Hz,
1H). 13C {1H} NMR (100 MHz, CDCl3): δ 179.6, 140.2, 139.6,
138.1, 131.0, 130.2, 127.7, 127.1, 127.1, 126.9, 118.7, 64.9, 46.6, 32.6,
20.6, 14.0. IR νmax (cm−1): 3060, 2956, 2620, 1732, 1704, 1635, 1500,
1443, 1395, 1258, 922, 711. HRMS (ESI) m/z: [M + Na]+ Calcd for
C20H22NaO2 317.1510; found 317.1512.
2-(6-Methoxynaphthalen-2-yl)-2-methylpent-4-enoic Acid (1al).
Synthesized from pentylbenzene according to the literature.28a
Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 10:1) as a white solid (1.5 g, 54% yield). mp
1
152.1−152.9 °C. H NMR (400 MHz, CDCl3): δ 7.71 (dd, J = 8.8,
1.6 Hz, 3H), 7.48 (dd, J = 8.8, 2.0 Hz, 1H), 7.19−7.08 (m, 2H), 5.63
(ddt, J = 17.2, 10.0, 7.2 Hz, 1H), 5.15−4.97 (m, 2H), 3.92 (s, 3H),
2.90 (dd, J = 13.6, 7.2 Hz, 1H), 2.79 (dd, J = 13.6, 7.2 Hz, 1H), 1.65
(s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 182.0, 157.9, 137.4,
133.8, 133.5, 129.6, 128.7, 127.0, 125.2, 124.7, 119.0, 118.7, 105.5,
55.3, 49.6, 43.4, 22.2. IR νmax (cm−1): 3070, 2980, 2940, 1700, 1635,
EXPERIMENTAL SECTION
■
General Information. All of the reactions were carried out in
oven-dried glassware with magnetic stirring. Unless otherwise
indicated, all solvents, reagents, and all deuterated solvents were
obtained from the commercial provider and used without further
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1605, 1460, 1395, 1267, 1220, 1165, 1027, 920, 850, 814, 475. HRMS
(ESI) m/z: [M + Na]+ Calcd for C17H18NaO3 293.1148; found
293.1144.
eluent was petroleum ether/EtOAc 4:1) as a white solid (62.3 mg,
65%). mp 59.6−60.3 °C. 1H NMR (400 MHz, CDCl3): δ 7.98 (d, J =
8.4 Hz, 4H), 7.38 (d, J = 8.0 Hz, 4H), 4.76−4.69 (m, 1H), 4.09 (dd, J
= 16.0, 7.6 Hz, 1H), 3.69 (dd, J = 15.6, 4.8 Hz, 1H), 2.49 (s, 6H),
2.05 (dd, J = 13.6, 6.8 Hz, 1H), 1.87 (dd, J = 13.2, 9.2 Hz, 1H), 1.64−
1.57 (m, 4H), 0.91 (td, J = 7.6, 2.4 Hz, 6H). 13C {1H} NMR (100
MHz, CDCl3): δ 179.6, 145.3, 136.3, 129.7, 128.7, 75.1, 53.4, 52.3,
48.4, 34.9, 29.1, 28.3, 21.7, 8.6. IR νmax (cm−1): 2960, 2925, 2854,
1770, 1683, 1653, 1558, 1456, 1373, 1265, 1167, 948, 811, 727, 663,
551. HRMS (ESI) m/z: [M + Na]+ Calcd for C23H29NNaO6S2
502.1329; found 502.1324.
2-Vinylcyclohexane-1-carboxylic Acid (1am). Synthesized from
hexahydroisobenzofuran-1,3-dione according to the literature.28g
Purified by silica gel column chromatography (the eluent was
1
petroleum ether/EtOAc 3:1) as a colorless oil (1.5 g, 40% yield). H
NMR (400 MHz, CDCl3) δ 11.81 (s, 1H), 5.98 (ddd, J = 17.2, 10.4,
8.0 Hz, 1H), 5.13−5.00 (m, 2H), 2.72−2.65 (m, 1H), 2.61 (dt, J =
8.8, 4.4 Hz, 1H), 1.86−1.69 (m, 4H), 1.64−1.56 (m, 2H), 1.48−1.30
(m, 2H).
General Procedures for Nitrogen Reagents. All nitrogen
reagents are known compounds that are commercially available or
prepared by the literature.29
4-Methyl-N-((5-oxo-4,4-dipropyltetrahydrofuran-2-yl)methyl)-N-
tosylbenzenesulfonamide (2d). Synthesized from 1d according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 4:1) as a white solid (77.1 mg,
76%). mp 95.8−96.3 °C. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J =
8.0 Hz, 4H), 7.35 (d, J = 8.0 Hz, 4H), 4.73−4.61 (m, 1H), 4.06 (dd, J
= 15.6, 7.2 Hz, 1H), 3.68 (dd, J = 15.6, 4.4 Hz, 1H), 2.45 (s, 6H),
2.03 (dd, J = 13.2, 6.8 Hz, 1H), 1.85 (dd, J = 12.8, 9.2 Hz, 1H), 1.58−
1.15 (m, 8H), 0.94−0.84 (m, 6H). 13C {1H} NMR (100 MHz,
CDCl3): δ 179.9, 145.3, 136.2, 129.7, 128.7, 75.3, 52.2, 47.8, 39.0,
38.4, 35.7, 21.7, 17.6, 17.6, 14.4, 14.4. IR νmax (cm−1): 2961, 2933,
2873, 1772, 1685, 1652, 1558, 1376, 1167, 1084, 816, 663, 547.
HRMS (ESI) m/z: [M + Na]+ Calcd for C25H33NNaO6S2 530.1642;
found 530.1645.
4-Methyl-N-((5-oxo-4,4-diphenyltetrahydrofuran-2-yl)methyl)-
N-tosylbenzenesulfonamide (2e). Synthesized from 1e according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 5:1) as a white solid (109.3 mg,
95%). mp 171.3−171.8 °C. 1H NMR (400 MHz, CDCl3): δ 7.92 (d, J
= 8.0 Hz, 4H), 7.36−7.21 (m, 14H), 4.64−4.58 (m, 1H), 4.16 (dd, J
= 15.6, 6.4 Hz, 1H), 3.88 (dd, J = 15.6, 4.8 Hz, 1H), 2.95 (dd, J =
13.2, 5.2 Hz, 1H), 2.69 (dd, J = 12.8, 10.8 Hz, 1H), 2.43 (s, 6H). 13C
{1H} NMR (100 MHz, CDCl3): δ 176.0, 145.4, 141.4, 139.4, 136.3,
129.8, 129.0, 128.6, 128.4, 127.8, 127.7, 127.3, 127.2, 75.2, 57.8, 51.2,
41.0, 21.7. IR νmax (cm−1): 3060, 3030, 2962, 2925, 2855, 1771, 1683,
1652, 1558, 1373, 1165, 1083, 966, 945, 817, 700, 665, 551. HRMS
(ESI) m/z: [M + Na]+ Calcd for C31H29NNaO6S2 598.1329; found
598.1335.
General Procedures for Amino Lactones. Procedure A. A 10
mL Pyrex tube was charged with substrates 1 (0.2 mmol), mCPBA
(0.35 mmol, 71 mg, 85 wt %), HNTs2 (0.3 mmol, 98 mg), and I11
(0.02 mmol, 5.3 mg) in CH3CN (2 mL), which was stirred at room
temperature for 2.5−5 h. The reaction solution was detected by TLC
until completely finished. After completion, the mixture was quenched
with an aqueous solution of NaOH (2 mol/L). The mixture was
extracted with EtOAc (20 mL × 3). The combined organic phase was
washed with brine, dried over Na2SO4, filtered, and concentrated
under vacuum. Then, the residue was purified by flash chromatog-
raphy on silica gel (PE/EtOAc = 10:1−1:1) to afford the desired
products 2.
Procedure B. A 10 mL Pyrex tube was charged with substrates 3
(0.2 mmol), mCPBA (0.35 mmol, 71 mg, 85 wt %), HNTs2 (0.3
mmol, 98 mg), and I11 (0.03 mmol, 7.9 mg) in HFIP (3 mL), which
was stirred at room temperature for 5−10 h. The reaction solution
was detected by TLC until completely finished. After completion, the
mixture was quenched with an aqueous solution of NaOH (2 mol/L).
The mixture was extracted with EtOAc (20 mL × 3). The combined
organic phase was washed with brine, dried over Na2SO4, filtered, and
concentrated under vacuum. Then, the residue was purified by flash
chromatography on silica gel (PE/EtOAc = 5:1−3:1) to afford the
desired products 4. Substrate 3e used I1 (0.03 mmol, 6.1 mg) instead
of I11, and substrate 3f used CH3CN (3 mL) as solvent.
1H NMR Experiments. An NMR tube was charged with substrates
(0.05 mmol), mCPBA (1.75 equiv, 85 wt %), I11 (10 mol % or 15
mol %), and HNTs2 (1.5 equiv), in CD3CN (0.5 mL) with CH2Br2
(0.05 mmol) as an internal standard.
5-(Hydroxymethyl)-3,3-diphenyldihydrofuran-2(3H)-one (2e′).
Synthesized from 1e via control experiment, sticky solid.30 1H
NMR (400 MHz, CDCl3): δ 7.40−7.27 (m, 9H), 7.26−7.21 (m, 1H),
4.51−4.40 (m, 1H), 3.95 (dd, J = 12.8, 2.4 Hz, 1H), 3.68 (dd, J =
12.8, 4.4 Hz, 1H), 3.02−2.84 (m, 2H), 2.64 (s, 1H). 13C {1H} NMR
(100 MHz, CDCl3): δ 177.3, 141.8, 139.8, 129.0, 128.4, 127.8, 127.8,
127.3, 127.3, 63.0, 58.3, 38.3.
4-Methyl-N-((5-oxotetrahydrofuran-2-yl)methyl)-N-tosylbenze-
nesulfonamide (2a). Synthesized from 1a according to the procedure
A. Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 1:1) as a white solid (63.5 mg, 75%). mp
1
59.8−60.6 °C. H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.4 Hz,
N-((4,4-Bis(4-methoxyphenyl)-5-oxotetrahydrofuran-2-yl)-
methyl)-4-methyl-N-tosylbenzenesulfonamide (2f). Synthesized
from 1f according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 2:1) as a
4H), 7.35 (d, J = 8.0 Hz, 4H), 4.86−4.79 (m, 1H), 4.07 (dd, J = 15.6,
7.6 Hz, 1H), 3.65 (dd, J = 15.6, 4.4 Hz, 1H), 2.56−2.47 (m, 2H), 2.45
(s, 6H), 2.34−2.21 (m, 1H), 1.95 (ddd, J = 16.8, 13.2, 8.8 Hz, 1H).
13C {1H} NMR (100 MHz, CDCl3): δ 176.0, 145.4, 136.1, 129.7,
1
white solid (85.1 mg, 67%). mp 92.9−93.9 °C. H NMR (400 MHz,
128.7, 78.5, 51.2, 28.0, 25.2, 21.7. IR νmax (cm−1): 2925, 1780, 1683,
1653, 1558, 1373, 1165, 1083, 816, 664, 550. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C19H21NNaO6S2 446.0702; found 446.0716.
N-((4,4-Dimethyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-
N-tosylbenzenesulfonamide (2b). Synthesized from 1b according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (77.6 mg,
86%). mp 166.3−167.4 °C. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J
= 7.6 Hz, 4H), 7.35 (d, J = 8.0 Hz, 4H), 4.78−4.67 (m, 1H), 4.10
(dd, J = 15.6, 7.2 Hz, 1H), 3.70 (dd, J = 16.0, 3.6 Hz, 1H), 2.45 (s,
6H), 2.10 (dd, J = 12.8, 6.0 Hz, 1H), 1.80−1.74 (m, 1H), 1.23 (s,
3H), 1.20 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 180.6,
145.3, 136.2, 129.7, 128.7, 75.3, 51.9, 40.6, 40.1, 24.9, 24.4, 21.7. IR
νmax (cm−1): 2970, 2932, 2876, 2360, 2340, 1775, 1657, 1558, 1373,
1166, 815, 664, 550. HRMS (ESI) m/z: [M + Na]+ Calcd for
C21H25NNaO6S2 474.1016; found 474.1016.
CDCl3): δ 7.92 (d, J = 8.4 Hz, 4H), 7.31 (d, J = 8.0 Hz, 4H), 7.13
(dd, J = 18.8, 8.8 Hz, 4H), 6.83 (dd, J = 15.2, 8.8 Hz, 4H), 4.63−4.56
(m, 1H), 4.14 (dd, J = 16.0, 6.4 Hz, 1H), 3.85 (dd, J = 15.6, 4.8 Hz,
1H), 3.80 (s, 3H), 3.77 (s, 3H), 2.89 (dd, J = 12.8, 4.8 Hz, 1H), 2.61
(dd, J = 13.2, 10.4 Hz, 1H), 2.43 (s, 6H). 13C {1H} NMR (100 MHz,
CDCl3): δ 176.6, 159.0, 158.61, 145.4, 136.2, 133.9, 131.4, 129.8,
128.8, 128.6, 128.3, 114.2, 113.7, 75.2, 56.6, 55.3, 55.2, 51.2, 41.2,
21.7. IR νmax (cm−1): 2955, 2935, 2835, 1772, 1684, 1653, 1558,
1506, 1375, 1254, 1165, 816, 664, 550. HRMS (ESI) m/z: [M + Na]+
Calcd for C33H33NNaO8S2 658.1540; found 658.1534.
N-((4,4-Dibenzyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-
N-tosylbenzenesulfonamide (2g). Synthesized from 1g according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 5:1) as a white solid (96.5 mg,
80%). mp 197.2−197.5 °C. 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J
= 8.4 Hz, 4H), 7.36−7.27 (m, 10H), 7.21−7.16 (m, 4H), 3.71−3.64
(m, 1H), 3.37 (dd, J = 15.6, 6.8 Hz, 1H), 3.20 (d, J = 13.6 Hz, 1H),
3.16−3.10 (m, 2H), 2.74 (dd, J = 17.6, 13.6 Hz, 2H), 2.46 (s, 6H),
2.16 (dd, J = 13.6, 7.6 Hz, 1H), 1.93 (dd, J = 13.6, 9.2 Hz, 1H). 13C
N-((4,4-Diethyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-N-
tosylbenzenesulfonamide (2c). Synthesized from 1c according to the
procedure A. Purified by silica gel column chromatography (the
5157
https://doi.org/10.1021/acs.joc.1c00074
J. Org. Chem. 2021, 86, 5152−5165

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
{1H} NMR (100 MHz, CDCl3): δ 179.8, 145.1, 136.5, 136.1, 135.9,
130.4, 129.9, 129.6, 128.7, 128.6, 127.4, 127.1, 75.2, 51.7, 51.5, 44.4,
43.4, 32.6, 21.7. IR νmax (cm−1): 3067, 3032, 2922, 1772, 1683, 1653,
1558, 1375, 1167, 1085, 816, 664, 550. HRMS (ESI) m/z: [M + Na]+
Calcd for C33H33NNaO6S2 626.1642; found 626.1640.
N-((3,3-Dimethyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-
N-tosylbenzenesulfonamide (2h). Synthesized from 1h according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (45.1 mg,
50%). mp 204.9−205.6 °C. 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J
= 8.4 Hz, 4H), 7.37 (d, J = 8.0 Hz, 4H), 4.47 (d, J = 9.2 Hz, 1H), 4.15
(dd, J = 16.0, 9.6 Hz, 1H), 3.55 (d, J = 16.0 Hz, 1H), 2.46 (s, 6H),
2.38 (d, J = 16.8 Hz, 1H), 2.31 (d, J = 16.8 Hz, 1H), 1.24 (s, 3H),
1.06 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 174.7, 145.6,
136.2, 129.6, 128.9, 86.6, 48.1, 44.2, 38.9, 25.2, 21.7, 21.0. IR νmax
(cm−1): 2963, 1792, 1772, 1734, 1683, 1653, 1520, 1506, 1372, 1165,
847, 664, 550. HRMS (ESI) m/z: [M + Na]+ Calcd for
C21H25NNaO6S2 474.1016; found 474.1030.
4-Methyl-N-tosyl-N-((2,4,4-trimethyl-5-oxotetrahydrofuran-2-
yl)methyl)benzenesulfonamide (2i). Synthesized from 1i according
to the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (45.6 mg,
49%). mp 101.2−102.3 °C. 1H NMR (400 MHz, CDCl3): δ 7.98 (d, J
= 8.4 Hz, 4H), 7.34 (d, J = 8.4 Hz, 4H), 4.01 (d, J = 1.6 Hz, 2H), 2.44
(s, 6H), 2.16 (d, J = 13.6 Hz, 1H), 1.92 (d, J = 13.6 Hz, 1H), 1.38 (s,
3H), 1.29 (s, 3H), 1.06 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3):
δ 180.9, 145.1, 136.8, 129.6, 128.9, 81.8, 56.7, 45.4, 40.4, 27.4, 27.1,
26.3, 21.7. IR νmax (cm−1): 2974, 2934, 2870, 1767, 1683, 1652, 1506,
1375, 1168, 1084, 937, 815, 766, 664, 552. HRMS (ESI) m/z: [M +
Na]+ Calcd for C22H27NNaO6S2 488.1172; found 488.1173.
1272, 1165, 1084, 1040, 815, 664, 551. HRMS (ESI) m/z: [M + Na]+
Calcd for C22H25NNaO6S2 486.1016; found 486.1021.
4-Methyl-N-((1-oxo-2-oxaspiro[4.4]nonan-3-yl)methyl)-N-tosyl-
benzenesulfonamide (2m). Synthesized from 1m according to the
procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (72.5 mg,
76%). mp 155.9−156.6 °C. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J
= 8.4 Hz, 4H), 7.34 (d, J = 8.0 Hz, 4H), 4.73−4.62 (m, 1H), 4.10
(dd, J = 15.6, 7.2 Hz, 1H), 3.69 (dd, J = 16.0, 4.4 Hz, 1H), 2.44 (s,
6H), 2.15−2.07 (m, 2H), 1.86−1.76 (m, 4H), 1.65−1.49 (m, 4H).
13C {1H} NMR (100 MHz, CDCl3): δ 181.2, 145.3, 136.2, 129.7,
128.7, 75.9, 51.7, 49.8, 40.2, 37.4, 36.9, 25.4, 25.4, 21.7. IR νmax
(cm−1): 2925, 2855, 1771, 1683, 1653, 1558, 1508, 1455, 1373, 1164,
1084, 947, 920, 813, 750, 662, 550. HRMS (ESI) m/z: [M + Na]+
Calcd for C23H27NNaO6S2 500.1172; found 500.1176.
4-Methyl-N-((1-oxo-2-oxaspiro[4.5]decan-3-yl)methyl)-N-tosyl-
benzenesulfonamide (2n). Synthesized from 1n according to the
procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (60.0 mg,
61%). mp 151.4−152.2 °C. 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J
= 8.0 Hz, 4H), 7.35 (d, J = 8.0 Hz, 4H), 4.74−4.67 (m, 1H), 4.09
(dd, J = 15.6, 7.2 Hz, 1H), 3.69 (dd, J = 16.0, 4.4 Hz, 1H), 2.45 (s,
6H), 2.25 (dd, J = 12.8, 6.4 Hz, 1H), 1.81−1.55 (m, 6H), 1.43 (d, J =
13.2 Hz, 1H), 1.36−1.18 (m, 4H). 13C {1H} NMR (100 MHz,
CDCl3): δ 180.3, 145.3, 136.2, 129.7, 128.7, 75.5, 52.1, 44.6, 36.6,
34.1, 31.7, 25.2, 22.1, 22.0, 21.7. IR νmax (cm−1): 2925, 2852, 1770,
1683, 1653, 1597, 1558, 1456, 1373, 1310, 1295, 1265, 1162, 1087,
1027, 943, 930, 815, 737, 660, 547. HRMS (ESI) m/z: [M + Na]+
Calcd for C24H29NNaO6S2 514.1329; found 514.1331.
4-Methyl-N-((1-oxo-2,8-dioxaspiro[4.5]decan-3-yl)methyl)-N-to-
sylbenzenesulfonamide (2o). Synthesized from 1o according to the
procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 1:1) as a white solid (67.0 mg,
68%). mp 183.5−184.4 °C. 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J
= 8.4 Hz, 4H), 7.36 (d, J = 8.0 Hz, 4H), 4.80−4.73 (m, 1H), 4.11
(dd, J = 15.6, 7.2 Hz, 1H), 4.02 (dt, J = 11.6, 4.4 Hz, 1H), 3.89 (dt, J
= 12.4, 4.0 Hz, 1H), 3.71 (dd, J = 15.6, 4.4 Hz, 1H), 3.57−3.41 (m,
2H), 2.46 (s, 6H), 2.33 (dd, J = 12.8, 6.4 Hz, 1H), 2.04 (ddd, J =
13.6, 10.0, 4.0 Hz, 1H), 1.92−1.74 (m, 2H), 1.53−1.39 (m, 2H). 13C
{1H} NMR (100 MHz, CDCl3): δ 178.6, 145.4, 136.1, 129.7, 128.7,
75.4, 63.9, 63.6, 51.8, 41.9, 37.2, 33.6, 32.0, 21.7. IR νmax (cm−1):
2955, 2855, 1773, 1652, 1558, 1375, 1165, 1085, 816, 664, 550.
HRMS (ESI) m/z: [M + Na]+ Calcd for C23H27NNaO7S2 516.1121;
found 516.1125.
4-Methyl-N-((2-methyl-5-oxo-4,4-diphenyltetrahydrofuran-2-yl)-
methyl)-N-tosylbenzenesulfonamide (2j). Synthesized from 1j
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
1
white solid (76.6 mg, 65%). mp 271.9−272.7 °C. H NMR (400
MHz, CDCl3): δ 7.95 (d, J = 8.0 Hz, 4H), 7.37−7.31 (m, 4H), 7.25−
7.20 (m, 8H), 7.10−7.07 (m, 2H), 4.24 (d, J = 16.4 Hz, 1H), 3.94 (d,
J = 16.4 Hz, 1H), 3.21 (d, J = 14.0 Hz, 1H), 2.92 (d, J = 14.0 Hz, 1H),
2.37 (s, 6H), 1.14 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
175.7, 145.1, 142.6, 142.1, 136.7, 129.6, 128.9, 128.6, 128.4, 127.4,
127.3, 127.2, 127.0, 82.9, 57.8, 56.2, 44.8, 24.9, 21.7. IR νmax (cm−1):
3060, 3030, 1766, 1666, 1597, 1492, 1447, 1370, 1168, 1085, 815,
775, 730, 700, 665, 550. HRMS (ESI) m/z: [M + Na]+ Calcd for
C32H31NNaO6S2 612.1485; found 612.1498.
(E)-4-Methyl-N-(1-(5-oxo-4,4-diphenyltetrahydrofuran-2-yl)-
ethyl)-N-tosylbenzenesulfonamide (2k). Synthesized from 1k
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
tert-Butyl 3-(((4-Methyl-N-tosylphenyl)sulfonamido)methyl)-1-
oxo-2-oxa-8-azaspiro[4.5]decane-8-carboxylate (2p). Synthesized
from 1p according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 3:1) as a
1
1
white solid (58.9 mg, 50%), dr > 20:1. mp 82.4−83.6 °C. H NMR
white solid (82.9 mg, 70%). mp 72.5−73.6 °C. H NMR (400 MHz,
(400 MHz, CDCl3): δ 7.97−7.74 (m, 4H), 7.37−7.29 (m, 12H), 7.20
(d, J = 7.2 Hz, 2H), 4.97 (td, J = 9.6, 5.2 Hz, 1H), 4.26 (dq, J = 15.2,
8.0, 7.2 Hz, 1H), 3.11 (dd, J = 13.2, 5.2 Hz, 1H), 2.44 (s, 6H), 2.40
(d, J = 4.0 Hz, 1H), 1.46−1.42 (m, 3H). 13C {1H} NMR (100 MHz,
CDCl3): δ 175.1, 141.7, 139.1, 129.3, 128.8, 128.7, 128.4, 128.3,
128.2, 127.7, 127.3, 127.1, 127.0, 76.2, 61.8, 57.7, 42.0, 21.4, 15.5. IR
νmax (cm−1): 3075, 2925, 2854, 2360, 2260, 1777, 1597, 1495, 1450,
1372, 1165, 1084, 1052, 967, 915, 858, 740, 697, 667, 550. HRMS
(ESI) m/z: [M + Na]+ Calcd for C32H31NNaO6S2 612.1485; found
612.1475.
4-Methyl-N-((5-oxo-6-oxaspiro[3.4]octan-7-yl)methyl)-N-tosyl-
benzenesulfonamide (2l). Synthesized from 1l according to the
procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 5:1) as a white solid (47.2 mg,
51%). mp 150.9−151.6 °C. 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J
= 7.6 Hz, 4H), 7.35 (d, J = 7.6 Hz, 4H), 4.69−4.60 (m, 1H), 4.01
(dd, J = 15.6, 7.6 Hz, 1H), 3.68−3.58 (m, 1H), 2.56−2.49 (m, 1H),
2.45 (s, 6H), 2.42−2.36 (m, 2H), 2.17−2.07 (m, 1H), 2.05−1.95 (m,
4H). 13C {1H} NMR (100 MHz, CDCl3): δ 179.9, 145.3, 136.1,
129.7, 128.7, 75.5, 51.5, 43.8, 39.0, 31.3, 29.8, 21.7, 16.4. IR νmax
(cm−1): 2990, 2937, 2865, 2360, 1773, 1684, 1654, 1599, 1373, 1295,
CDCl3): δ 7.94 (d, J = 8.4 Hz, 4H), 7.35 (d, J = 8.4 Hz, 4H), 4.79−
4.72 (m, 1H), 4.10 (dd, J = 15.6, 7.2 Hz, 1H), 3.92 (s, 1H), 3.80 (s,
1H), 3.71 (dd, J = 15.6, 4.4 Hz, 1H), 3.04 (dt, J = 23.4, 10.6 Hz, 2H),
2.45 (s, 6H), 2.24 (dd, J = 13.2, 6.4 Hz, 1H), 1.88 (ddd, J = 13.8,
10.0, 4.0 Hz, 1H), 1.79−1.69 (m, 2H), 1.51 (dd, J = 15.6, 6.4 Hz,
2H), 1.45 (s, 9H). 13C {1H} NMR (100 MHz, CDCl3): δ 178.7,
154.6, 145.5, 136.1, 129.7, 128.7, 79.9, 75.5, 51.8, 42.7, 36.6, 33.2,
31.5, 28.4, 21.7. IR νmax (cm−1): 2977, 2930, 1771, 1690, 1682, 1653,
1596, 1425, 1370, 1282, 1265, 1252, 1165, 1085, 1045, 818, 790, 664,
552. HRMS (ESI) m/z: [M + Na]+ Calcd for C28H36N2NaO8S2
615.1805; found 615.1812.
4-Methyl-N-((2′-oxo-4′,5′-dihydro-2′H-spiro[fluorene-9,3′-
furan]-5′-yl)methyl)-N-tosylbenzenesulfonamide (2q). Synthesized
from 1q according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
1
white solid (86.0 mg, 75%). mp 231.3−231.8 °C. H NMR (400
MHz, CDCl3): δ 8.03 (d, J = 8.4 Hz, 4H), 7.74 (d, J = 7.6 Hz, 2H),
7.47−7.40 (m, 2H), 7.39−7.28 (m, 8H), 5.34−5.27 (m, 1H), 4.39
(dd, J = 15.8, 7.2 Hz, 1H), 3.98 (dd, J = 15.8, 4.4 Hz, 1H), 2.72 (dd, J
= 13.6, 10.4 Hz, 1H), 2.61 (dd, J = 13.6, 6.4 Hz, 1H), 2.44 (s, 6H).
13C {1H} NMR (100 MHz, CDCl3): δ 175.7, 145.5, 145.4, 144.6,
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141.4, 140.6, 136.2, 129.8, 129.0, 128.9, 128.8, 128.3, 128.1, 123.6,
122.8, 120.7, 120.4, 76.6, 58.5, 52.1, 38.9, 21.7. IR νmax (cm−1): 3068,
2925, 1780, 1685, 1597, 1450, 1375, 1165, 817, 735, 667, 550. HRMS
(ESI) m/z: [M + Na]+ Calcd for C31H27NNaO6S2 596.1172; found
596.1177.
5′-(Hydroxymethyl)-4′,5′-dihydro-2′H-spiro[fluorene-9,3′-
furan]-2′-one (2q′). Byproduct of 2q, yellow solid. mp 123.9−130.6
°C. 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 6.4 Hz, 2H), 7.56 (d,
J = 7.2 Hz, 1H), 7.46−7.38 (m, 4H), 7.32 (dd, J = 8.8, 5.2 Hz, 1H),
4.92 (dq, J = 10.4, 6.4, 5.2 Hz, 1H), 3.63 (dt, J = 10.0, 5.2 Hz, 2H),
2.79 (tt, J = 9.6, 5.4 Hz, 2H). 13C {1H} NMR (100 MHz, CDCl3): δ
175.9, 145.8, 144.8, 141.4, 140.6, 129.0, 129.0, 128.4, 128.1, 123.8,
122.6, 120.8, 120.4, 75.9, 59.3, 42.3, 8.3. IR νmax (cm−1): 3067, 3018,
2925, 2852, 1775, 1683, 1448, 1332, 1155, 1011, 971, 752, 734.
HRMS (ESI) m/z: [M + Na]+ Calcd for C17H14NaO3 289.0835;
found 289.0835.
177.5, 145.4, 136.1, 129.7, 128.7, 76.9, 51.8, 42.0, 32.0, 23.3, 21.7,
11.6. IR νmax (cm−1): 2965, 2928, 1770, 1597, 1558, 1456, 1375,
1260, 1167, 1084, 945, 816, 664, 550. HRMS (ESI) m/z: [M + Na]+
Calcd for C21H25NNaO6S2 474.1016; found 474.1023.
N-((4-Isopropyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-N-
tosylbenzenesulfonamide (2ac). Synthesized from 1ac according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (77.2 mg,
83%). The product was obtained as a mixture of two inseparable
isomers with dr = 3.3:1. mp 142.7−143.6 °C. For major isomer
shown: 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.4 Hz, 4H), 7.34
(d, J = 8.4 Hz, 4H), 4.67−4.60 (m, 1H), 4.08 (dd, J = 15.6, 6.8 Hz,
1H), 3.72 (dd, J = 16.0, 4.4 Hz, 1H), 2.61−2.46 (m, 1H), 2.44 (s,
6H), 2.26−1.97 (m, 2H), 1.69−1.60 (m, 1H), 1.00 (d, J = 6.8 Hz,
3H), 0.87 (d, J = 6.8 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
176.7, 145.4, 136.2, 129.7, 128.7, 76.6, 51.8, 46.6, 28.1, 27.6, 21.7,
20.6, 18.3. IR νmax (cm−1): 2960, 2875, 2360, 1775, 1653, 1600, 1558,
1373, 1165, 1084, 817, 663, 550. HRMS (ESI) m/z: [M + Na]+ Calcd
for C22H27NNaO6S2 488.1172; found 488.1172.
N-((4-(tert-Butyl)-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-
N-tosylbenzenesulfonamide (2ad). Synthesized from 1ad according
to the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (63.2 mg,
66%). The product was obtained as a mixture of two inseparable
isomers with dr = 2.9:1. mp 197.5−198.3 °C. For major isomer
shown: 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.0 Hz, 4H), 7.35
(d, J = 8.0 Hz, 4H), 4.57 (dd, J = 10.4, 5.2 Hz, 1H), 4.08 (dd, J =
16.0, 6.8 Hz, 1H), 3.72 (dd, J = 15.6, 4.0 Hz, 1H), 2.45 (s, 6H), 2.42−
2.38 (m, 1H), 2.26−2.20 (m, 1H), 1.68 (q, J = 11.8 Hz, 1H), 1.01 (s,
9H). 13C {1H} NMR (100 MHz, CDCl3): δ 175.5, 145.3, 136.2,
129.7, 128.7, 75.7, 51.8, 50.4, 31.7, 29.4, 27.1, 21.7. IR νmax (cm−1):
2962, 2872, 1770, 1683, 1654, 1597, 1558, 1385, 1166, 1084, 815,
663, 550. HRMS (ESI) m/z: [M + Na]+ Calcd for C23H29NNaO6S2
502.1329; found 502.1336.
N,N′-((1,6-Dioxo-2,7-dioxaspiro[4.4]nonane-3,8-diyl)bis(met-
ylene))bis(4-methyl-N-tosylbenzenesulfonamide) (2r). Synthesized
from 1r according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 3:1) as a
1
white solid (116.3 mg, 70%). mp 134.5−135.6 °C. H NMR (400
MHz, CDCl3): δ 7.94 (d, J = 8.0 Hz, 8H), 7.36 (d, J = 8.0 Hz, 8H),
5.14−5.07 (m, 2H), 4.08 (dd, J = 15.6, 6.8 Hz, 2H), 3.73 (dd, J =
15.6, 5.2 Hz, 2H), 2.66 (dd, J = 13.6, 6.8 Hz, 2H), 2.45 (s, 12H), 2.04
(dd, J = 13.2, 8.8 Hz, 2H). 13C {1H} NMR (100 MHz, CDCl3): δ
172.0, 145.6, 136.0, 129.9, 128.6, 76.6, 52.2, 50.6, 35.7, 21.7. IR νmax
(cm−1): 3070, 2962, 2927, 1770, 1653, 1597, 1558, 1495, 1373, 1295,
1265, 1167, 1084, 921, 812, 738, 665, 580, 554. HRMS (ESI) m/z:
[M + Na]+ Calcd for C37H38N2NaO12S4 853.1200; found 853.1205.
Ethyl 3-allyl-5-(((4-methyl-N-tosylphenyl)sulfonamido)methyl)-
2-oxotetrahydrofuran-3-carboxylate (2s). Synthesized from 1s
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 3:1) as a
1
white solid (45.0 mg, 42%), dr > 20:1. mp 56.7−58.3 °C. H NMR
(400 MHz, CDCl3): δ 7.95 (d, J = 7.6 Hz, 4H), 7.36 (d, J = 8.0 Hz,
4H), 5.62 (dq, J = 16.8, 7.2 Hz, 1H), 5.21−5.11 (m, 2H), 4.91−4.82
(m, 1H), 4.29−4.14 (m, 2H), 4.09 (dd, J = 15.6, 6.8 Hz, 1H), 3.75−
3.67 (m, 1H), 2.73 (dd, J = 14.0, 8.0 Hz, 1H), 2.63 (dd, J = 13.6, 6.0
Hz, 1H), 2.52 (dd, J = 14.4, 6.8 Hz, 1H), 2.46 (s, 6H), 1.99−1.88 (m,
1H), 1.27 (t, J = 7.2 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
172.7, 168.8, 145.4, 136.1, 131.7, 129.7, 128.7, 120.5, 77.2, 62.5, 55.3,
51.4, 38.3, 34.7, 21.7, 14.0. IR νmax (cm−1): 2985, 2917, 2857, 1785,
1734, 1683, 1653, 1375, 1297, 1165, 1083, 920, 820, 664, 551. HRMS
(ESI) m/z: [M + Na]+ Calcd for C25H29NNaO8S2 558.1227; found
558.1222.
4-Methyl-N-((4-methyl-5-oxotetrahydrofuran-2-yl)methyl)-N-to-
sylbenzenesulfonamide (2aa). Synthesized from 1aa according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (61.2 mg,
70%). The product was obtained as a mixture of two inseparable
isomers with dr = 2.3:1. mp 69.8−70.3 °C. For major isomer shown:
1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.4 Hz, 4H), 7.35 (d, J =
8.4 Hz, 4H), 4.71−4.60 (m, 1H), 4.10 (dd, J = 16.0, 7.2 Hz, 1H), 3.72
(dd, J = 16.0, 4.0 Hz, 1H), 2.76−2.56 (m, 2H), 2.46 (s, 6H), 1.60−
1.50 (m, 1H), 1.22 (d, J = 7.2 Hz, 3H). 13C {1H} NMR (100 MHz,
CDCl3): δ 178.2, 145.4, 136.2, 129.7, 128.7, 77.3, 51.7, 35.5, 34.6,
21.7, 15.0. IR νmax (cm−1): 2973, 2945, 2877, 1777, 1684, 1653, 1596,
1506, 1375, 1165, 1085, 1032, 816, 663, 550. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C20H23NNaO6S2 460.0859; found 460.0866.
N-((4-Ethyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-N-to-
sylbenzenesulfonamide (2ab). Synthesized from 1ab according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 2:1) as a white solid (70.4 mg,
78%). The product was obtained as a mixture of two inseparable
isomers with dr = 2.4:1. mp 130.9−132.6 °C. For major isomer
shown: 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.8 Hz, 4H), 7.34
(d, J = 8.2 Hz, 4H), 4.72−4.60 (m, 1H), 4.09 (dd, J = 15.6, 6.8 Hz,
1H), 3.72 (dd, J = 15.6, 4.4 Hz, 1H), 2.61−2.47 (m, 1H), 2.45 (s,
6H), 2.42−2.36 (m, 1H), 1.91−1.78 (m, 1H), 1.61−1.32 (m, 2H),
0.96 (d, J = 8.0 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ
4-Methyl-N-((5-oxo-4-phenyltetrahydrofuran-2-yl)methyl)-N-to-
sylbenzenesulfonamide (2ae). Synthesized from 1ae according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (70.9 mg,
71%). The product was obtained as a mixture of two inseparable
isomers with dr = 2.5:1. mp 81.9−82.5 °C. For major isomer shown:
1H NMR (400 MHz, CDCl3): δ 7.97 (dd, J = 8.0, 4.4 Hz, 4H), 7.39−
7.18 (m, 9H), 4.85−4.79 (m, 1H), 4.19 (dd, J = 16.0, 6.8 Hz, 1H),
3.88−3.78 (m, 2H), 2.73 (ddd, J = 13.2, 8.4, 5.6 Hz, 1H), 2.45 (s,
6H), 2.16−2.02 (m, 1H). 13C {1H} NMR (100 MHz, CDCl3): δ
175.5, 145.4, 136.1, 135.9, 129.7, 128.9, 128.8, 128.0, 127.8, 76.8,
51.5, 46.6, 35.2, 21.7. IR νmax (cm−1): 3065, 3030, 2926, 1780, 1684,
1652, 1506, 1374, 1165, 1084, 945, 817, 663, 552. HRMS (ESI) m/z:
[M + Na]+ Calcd for C25H25NNaO6S2 522.1016; found 522.1021.
N-((4-Benzyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-N-to-
sylbenzenesulfonamide (2af). Synthesized from 1af according to the
procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (67.7 mg,
66%). The product was obtained as a mixture of two inseparable
isomers with dr = 3.4:1. mp 190.4−190.7 °C. For major isomer
1
shown: H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.0 Hz, 4H),
7.37−7.14 (m, 9H), 4.68−4.59 (m, 1H), 4.04 (dd, J = 16.0, 7.2 Hz,
1H), 3.64 (dd, J = 16.0, 4.0 Hz, 1H), 3.26 (dd, J = 14.0, 4.0 Hz, 1H),
2.91−2.83 (m, 1H), 2.64 (dd, J = 14.0, 10.0 Hz, 1H), 2.45 (s, 6H),
2.26 (ddd, J = 13.6, 8.4, 6.0 Hz, 1H), 1.59 (q, J = 12.0 Hz, 1H). 13C
{1H} NMR (100 MHz, CDCl3): δ 176.8, 145.3, 138.3, 136.1, 129.7,
128.8, 128.7, 126.8, 77.2, 51.7, 42.4, 36.1, 32.3, 21.7. IR νmax (cm−1):
3066, 3032, 2925, 1776, 1683, 1652, 1558, 1374, 1165, 1084, 817,
663, 550. HRMS (ESI) m/z: [M + Na]+ Calcd for C26H27NNaO6S2
536.1172; found 536.1178.
4-Methyl-N-((3-methyl-5-oxo-4,4-diphenyltetrahydrofuran-2-yl)-
methyl)-N-tosylbenzenesulfonamide (2ag). Synthesized from 1ag
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 10:1) as a
white solid (106.0 mg, 90%). The product was obtained as a mixture
of two inseparable isomers with dr = 2.9:1. mp 118.2−119.0 °C. For
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Article
major isomer shown: 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.0
Hz, 4H), 7.50−7.18 (m, 12H), 6.82−6.80 (m, 2H), 4.25 (ddd, J =
22.8, 16.8, 7.6 Hz, 2H), 3.94−3.82 (m, 1H), 3.12−3.04 (m, 1H), 2.44
(d, J = 11.6 Hz, 6H), 0.89 (d, J = 6.8 Hz, 3H). 13C {1H} NMR (100
MHz, CDCl3): δ 176.4, 145.3, 139.6, 138.5, 136.4, 129.7, 128.9,
128.7, 128.6, 128.5, 128.4, 128.2, 80.7, 60.8, 50.8, 41.3, 21.7, 12.6. IR
νmax (cm−1): 3060, 2973, 1773, 1684, 1653, 1558, 1375, 1167, 1085,
816, 701, 664, 551. HRMS (ESI) m/z: [M + Na]+ Calcd for
C32H31NNaO6S2 612.1485; found 612.1487.
(E)-N-((3-Ethyl-5-oxo-4,4-diphenyltetrahydrofuran-2-yl)methyl)-
4-methyl-N-tosylbenzenesulfonamide (2ah). Synthesized from 1ah
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 2:1) as a
white solid (97.7 mg, 81%), dr > 20:1. mp 116.3−116.9 °C. 1H NMR
(400 MHz, CDCl3): δ 8.02 (d, J = 8.0 Hz, 4H), 7.46 (d, J = 7.2 Hz,
2H), 7.37 (d, J = 8.2 Hz, 6H), 7.29−7.21 (m, 4H), 6.90−6.79 (m,
2H), 4.50 (t, J = 8.4 Hz, 1H), 4.18 (dd, J = 15.6, 9.2 Hz, 1H), 3.85 (d,
J = 16.0 Hz, 1H), 2.88 (s, 1H), 2.47 (s, 6H), 1.25 (s, 2H), 1.02−0.97
(m, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 176.4, 145.2, 139.6,
139.3, 136.3, 129.6, 128.9, 128.6, 128.5, 128.4, 128.2, 127.8, 127.5,
80.8, 61.2, 52.2, 47.7, 22.2, 21.8, 12.9. IR νmax (cm−1): 2963, 2925,
2853, 1773, 1734, 1684, 1652, 1559, 1506, 1458, 1260, 1166, 1087,
1020, 810, 662, 550, 418. HRMS (ESI) m/z: [M + Na]+ Calcd for
C33H33NNaO6S2 626.1642; found 626.1643.
(E)-4-Methyl-N-((5-oxo-4,4-diphenyl-3-propyltetrahydrofuran-2-
yl)methyl)-N-tosylbenzenesulfonamide (2ai). Synthesized from 1ai
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 3:1) as a
white solid (80.2 mg, 65%), dr > 20:1. mp 200.7−201.3 °C. 1H NMR
(400 MHz, CDCl3): δ 8.02 (d, J = 7.6 Hz, 4H), 7.52−7.29 (m, 12H),
6.88 (s, 2H), 4.49 (t, J = 8.8 Hz, 1H), 4.19 (dd, J = 15.6, 9.2 Hz, 1H),
3.85 (d, J = 15.6 Hz, 1H), 3.03−2.91 (m, 1H), 2.46 (s, 6H), 1.45−
1.31 (m, 2H), 1.30−1.27 (m, 1H), 1.02 (dt, J = 13.2, 7.2 Hz, 1H),
0.86 (t, J = 6.8 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 176.5,
145.3, 139.7, 139.2, 136.3, 129.7, 128.9, 128.7, 128.6, 128.4, 128.2,
127.8, 127.6, 80.7, 61.3, 52.1, 46.0, 31.2, 21.8, 21.5, 14.4. IR νmax
(cm−1): 3062, 3032, 2960, 3932, 2873, 2257, 1775, 1653, 1495, 1445,
1375, 1352, 1307, 1292, 1167, 1085,1057, 912, 816, 735, 700, 663,
554. HRMS (ESI) m/z: [M + Na]+ Calcd for C34H35NNaO6S2
640.1798; found 640.1806.
664, 550. HRMS (ESI) m/z: [M + Na]+ Calcd for C26H27NNaO6S2
536.1172; found 536.1174.
N-((4-(7-Methoxynaphthalen-2-yl)-4-methyl-5-oxotetrahydro-
furan-2-yl)methyl)-4-methyl-N-tosylbenzenesulfonamide (2al).
Synthesized from 1al according to the procedure A. Purified by silica
gel column chromatography (the eluent was petroleum ether/EtOAc
5:1) as a white solid (47.4 mg, 40%). The product was obtained as a
mixture of two inseparable isomers with dr = 1.2:1. mp 85.1−86.6 °C.
For major isomer shown: 1H NMR (400 MHz, CDCl3): δ 7.88 (t, J =
7.6 Hz, 4H), 7.80−7.13 (m, 10H), 4.51−4.44 (m, 1H), 4.17 (dd, J =
15.6, 6.4 Hz, 1H), 3.92 (s, 3H), 3.84 (dd, J = 15.6, 5.2 Hz, 1H), 2.74
(dd, J = 13.0, 4.8 Hz, 1H), 2.41 (s, 6H), 2.18−2.07 (m, 1H), 1.58 (s,
3H). 13C {1H} NMR (100 MHz, CDCl3): δ 178.4, 158.1, 145.3,
136.3, 136.1, 133.7, 129.7, 129.6, 128.5, 127.9, 124.2, 124.1, 119.4,
105.5, 75.1, 55.4, 51.2, 49.7, 41.7, 26.2, 21.7. IR νmax (cm−1): 2965,
2925, 2855, 1771, 1683, 1652, 1505, 1454, 1372, 1265, 1166, 1087,
1035, 810, 661, 549. HRMS (ESI) m/z: [M + Na]+ Calcd for
C31H31NNaO7S2 616.1434; found 616.1439.
4-Methyl-N-((3-oxooctahydroisobenzofuran-1-yl)methyl)-N-to-
sylbenzenesulfonamide (2am). Synthesized from 1am according to
the procedure A. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (44.8 mg,
47%). The product was obtained as a mixture of three inseparable
isomers with dr = 3.8:1.8:1. mp 212.3−214.1 °C. For major isomer
shown: 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.0 Hz, 4H), 7.36
(d, J = 8.4 Hz, 4H), 4.62−4.50 (m, 1H), 4.22 (dd, J = 16.4, 8.4 Hz,
1H), 3.66 (dd, J = 16.4, 2.0 Hz, 1H), 2.66 (t, J = 6.0 Hz, 1H), 2.45 (s,
6H), 2.15 (d, J = 13.6 Hz, 1H), 2.04−0.95 (m, 8H). 13C {1H} NMR
(100 MHz, CDCl3): δ 176.6, 145.3, 136.3, 129.6, 128.8, 80.7, 48.5,
41.6, 38.3, 23.4, 22.6, 22.3, 22.3, 21.7. IR νmax (cm−1): 2934, 2858,
2360, 2345, 1777, 1653, 1558, 1375, 1165, 816, 664, 550. HRMS
(ESI) m/z: [M + Na]+ Calcd for C23H27NNaO6S2 500.1172; found
500.1174.
4-Methyl-N-((3-oxo-1,3-dihydroisobenzofuran-1-yl)methyl)-N-
tosylbenzenesulfonamide (4a). Synthesized from 3a according to
the procedure B. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (51.8 mg,
55%). mp 191.5−192.8 °C. 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J
= 8.4 Hz, 4H), 7.91 (d, J = 7.6 Hz, 1H), 7.67 (t, J = 7.4 Hz, 1H), 7.57
(t, J = 7.4 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.39 (d, J = 8.0 Hz, 4H),
5.82 (dd, J = 8.4, 2.8 Hz, 1H), 4.10 (dd, J = 16.0, 8.8 Hz, 1H), 3.96
(dd, J = 16.0, 3.2 Hz, 1H), 2.47 (s, 6H). 13C {1H} NMR (100 MHz,
CDCl3): δ 169.4, 146.2, 145.5, 136.1, 134.3, 130.0, 129.8, 128.8,
126.2, 126.1, 122.5, 80.0, 52.3, 21.8. IR νmax (cm−1): 3075, 2925,
2855, 1770, 1684, 1600, 1512, 1372, 1285, 1168, 1085, 1063, 1038,
930, 765, 724, 665, 552. HRMS (ESI) m/z: [M + Na]+ Calcd for
C23H21NNaO6S2 494.0702; found 494.0707.
N-((4-Ethyl-5-oxo-4-phenyltetrahydrofuran-2-yl)methyl)-4-
methyl-N-tosylbenzenesulfonamide (2aj). Synthesized from 1aj
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
white solid (98.0 mg, 93%). The product was obtained as a mixture of
two inseparable isomers with dr = 2.6:1. mp 72.8−73.9 °C. For major
1
isomer shown: H NMR (400 MHz, CDCl3): δ 7.92 (d, J = 8.0 Hz,
N-((5-Fluoro-3-oxo-1,3-dihydroisobenzofuran-1-yl)methyl)-4-
methyl-N-tosylbenzenesulfonamide (4b). Synthesized from 3b
according to the procedure B. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
4H), 7.50−7.27 (m, 9H), 4.52−4.45 (m, 1H), 4.14 (dd, J = 15.6, 6.0
Hz, 1H), 3.81 (dd, J = 15.6, 5.2 Hz, 1H), 2.67 (dd, J = 13.2, 4.8 Hz,
1H), 2.45 (d, J = 5.6 Hz, 6H), 2.06 (dd, J = 13.2, 10.8 Hz, 1H), 2.01−
1.88 (m, 2H), 0.83−0.75 (m, 3H). 13C {1H} NMR (100 MHz,
CDCl3): δ 177.5, 145.3, 137.8, 136.3, 129.7, 128.9, 128.6, 127.6,
126.2, 75.1, 53.5, 51.4, 37.2, 32.3, 21.7, 9.0. IR νmax (cm−1): 3060,
2970, 2934, 1775, 1654, 1597, 1492, 1447, 1375, 1352, 1166, 1084,
941, 913, 816, 664, 551. HRMS (ESI) m/z: [M + Na]+ Calcd for
C27H29NNaO6S2 550.1329; found 550.1336.
4-Methyl-N-((4-methyl-5-oxo-4-phenyltetrahydrofuran-2-yl)-
methyl)-N-tosylbenzenesulfonamide (2ak). Synthesized from 1ak
according to the procedure A. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 3:1) as a
white solid (80.0 mg, 78%). The product was obtained as a mixture of
two inseparable isomers with dr = 1.3:1. mp 72.5−72.8 °C. For major
isomer shown: 1H NMR (400 MHz, CDCl3): δ 7.92 (dd, J = 8.8, 4.4
Hz, 5H), 7.45−7.22 (m, 8H), 4.49−4.2 (m, 1H), 4.15 (dd, J = 15.6,
6.4 Hz, 1H), 3.80 (dd, J = 15.6, 5.2 Hz, 1H), 2.65 (dd, J = 13.2, 5.2
Hz, 1H), 2.46 (s, 6H), 2.07 (dd, J = 12.8, 11.2 Hz, 1H), 1.52 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3): δ 178.5, 145.3, 140.2, 136.3,
1
white solid (45.0 mg, 46%). mp 173.4−174.7 °C. H NMR (400
MHz, CDCl3): δ 7.99 (d, J = 8.0 Hz, 4H), 7.55 (d, J = 6.4 Hz, 1H),
7.49 (dd, J = 8.0, 4.0 Hz, 1H), 7.38 (d, J = 8.0 Hz, 4H), 7.37−7.33
(m, 1H), 5.80 (d, J = 5.2 Hz, 1H), 4.11 (dd, J = 16.0, 8.4 Hz, 1H),
3.94 (dd, J = 16.0, 2.8 Hz, 1H), 2.48 (s, 6H). 13C {1H} NMR (100
MHz, CDCl3): δ 168.1 (168.1), 164.8 (162.3), 145.5, 141.8 (141.7),
136.1, 129.7, 128.8, 128.4 (128.3), 124.5 (124.4), 122.3 (122.1),
112.6 (112.3), 79.8, 52.2, 21.7. IR νmax (cm−1): 3073, 2926, 2855,
1777, 1684, 1499, 1374, 1165, 1085, 1040, 923, 815, 720, 663, 549.
HRMS (ESI) m/z: [M + Na]+ Calcd for C23H20FNNaO6S2 512.0608;
found 512.0599.
N-((5-Chloro-3-oxo-1,3-dihydroisobenzofuran-1-yl)methyl)-4-
methyl-N-tosylbenzenesulfonamide (4c). Synthesized from 3c
according to the procedure B. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
1
white solid (45.5 mg, 45%). mp 191.3−192.6 °C. H NMR (400
MHz, CDCl3): δ 7.98 (d, J = 8.4 Hz, 4H), 7.86 (s, 1H), 7.58 (d, J =
8.4 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 8.4 Hz, 4H), 5.80
(dd, J = 8.0, 3.6 Hz, 1H), 4.11 (dd, J = 16.0, 8.4 Hz, 1H), 3.93 (dd, J
129.7, 129.0, 128.6, 127.6, 125.6, 75.0, 51.2, 49.6, 41.6, 26.3, 21.7. IR
νmax (cm−1): 2975, 2930, 1780, 1684, 1653, 1375, 1166, 1083, 815,
5160
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= 16.0, 3.6 Hz, 1H), 2.47 (s, 6H). 13C {1H} NMR (100 MHz,
CDCl3): δ 167.9, 145.6, 144.4, 136.4, 136.0, 134.5, 129.8, 128.7,
127.9, 125.88, 124.1, 79.7, 52.0, 21.8. IR νmax (cm−1): 3075, 2925,
2852, 2362, 2256, 1775, 1683, 1597, 1373, 1290, 1165, 1085, 1058,
1040, 930, 819, 663, 552. HRMS (ESI) m/z: [M + Na]+ Calcd for
C23H20ClNNaO6S2 528.0313; found 528.0304.
13.2, 10.2 Hz, 1H). 13C {1H} NMR (100 MHz, CDCl3): δ 176.0,
141.4, 139.4, 139.1, 134.3, 129.2, 129.0, 128.6, 128.5, 127.9, 127.7,
127.4, 127.2, 75.2, 57.8, 51.5, 41.0. IR νmax (cm−1): 3067, 3030, 2947,
2260, 1780, 1600, 1585, 1496, 1448, 1378, 1291, 1170, 1085, 1064,
965, 945, 913, 800, 740, 699, 685, 853,550. HRMS (ESI) m/z: [M +
Na]+ Calcd for C29H25NNaO6S2 570.1016; found 570.1011.
N-((5-Methoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)methyl)-4-
methyl-N-tosylbenzenesulfonamide (4e). Synthesized from 3e
according to the procedure B. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
4-Nitro-N-((4-nitrophenyl)sulfonyl)-N-((5-oxo-4,4-diphenyltetra-
hydrofuran-2-yl)methyl)benzenesulfonamide (2e-N4). Synthesized
from 1e. Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 4:1) as a white solid (108.3 mg, 85%). mp
1
1
white solid (54.1 mg, 54%). mp 158.9−160.4 °C. H NMR (400
163.9−164.7 °C. H NMR (400 MHz, CDCl3): δ 8.38−8.24 (m,
MHz, CDCl3): δ 7.93 (d, J = 8.4 Hz, 4H), 7.54 (s, 1H), 7.35 (d, J =
8.4 Hz, 4H), 7.11 (s, 2H), 6.39 (dd, J = 12.8, 3.2 Hz, 1H), 4.20 (dd, J
= 15.6, 12.8 Hz, 1H), 3.84 (s, 3H), 2.83 (dd, J = 15.6, 3.2 Hz, 1H),
2.46 (s, 6H). 13C {1H} NMR (100 MHz, CDCl3): δ 163.3, 159.3,
145.5, 136.9, 129.8, 129.5, 128.7, 128.6, 125.2, 122.2, 113.1, 85.8,
55.7, 32.5, 21.8. IR νmax (cm−1): 2930, 2836, 1734, 1682, 1652, 1558,
1506, 1377, 1282, 1169, 1052, 885, 814, 771, 738, 665, 550. HRMS
(ESI) m/z: [M + Na]+ Calcd for C24H23NNaO7S2 524.0808; found
524.0805.
8H), 7.33−7.26 (m, 4H), 7.26−7.17 (m, 6H), 4.63−4.53 (m, 1H),
4.22 (dd, J = 16.2, 8.0 Hz, 1H), 3.98−3.89 (m, 1H), 3.01 (dd, J =
13.2, 5.2 Hz, 1H), 2.61 (dd, J = 13.2, 10.0 Hz, 1H). 13C {1H} NMR
(100 MHz, CDCl3): δ 175.5, 150.9, 144.0, 140.9, 139.3, 130.3, 129.1,
128.6, 128.1, 127.7, 127.5, 127.0, 124.4, 75.3, 57.5, 52.5, 40.4. IR νmax
(cm−1): 3110, 3070, 3040, 2935, 2873, 2257, 1780, 1608, 1535, 1507,
1447, 1370, 1317, 1290, 965, 945, 912, 856, 800, 740, 613, 546, 470.
HRMS (ESI) m/z: [M + H]+ Calcd for C29H24N3O10S2 638.0898;
found 638.0893.
4-Methyl-N-((1-methyl-3-oxo-1,3-dihydroisobenzofuran-1-yl)-
methyl)-N-tosylbenzenesulfonamide (4f). Synthesized from 3f
according to the procedure B. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
4-Methyl-N-((5-oxo-4,4-diphenyltetrahydrofuran-2-yl)methyl)-
benzenesulfonamide (2e-N6). Synthesized from 1e. Purified by silica
gel column chromatography (the eluent was EtOAc) as a white solid
(46.3 mg, 55%). mp 106.2−107.0 °C. 1H NMR (400 MHz, CDCl3):
δ 7.98 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 4.0 Hz, 4H), 7.61−7.45 (m,
9H), 7.46 (d, J = 4.8 Hz, 2H), 4.70−4.62 (m, 1H), 4.17 (dd, J = 12.8,
2.4 Hz, 1H), 3.89 (dd, J = 12.8, 4.4 Hz, 1H), 3.20−3.11 (m, 1H), 3.08
(dd, J = 12.9, 5.3 Hz, 1H), 2.60 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3): δ 177.3, 143.5, 141.7, 139.7, 139.1, 129.7, 129.0, 128.4,
127.8, 127.8, 127.3, 127.3, 126.4, 63.0, 58.3, 38.3, 21.5. IR νmax
(cm−1): 3368, 3262, 3070, 2928, 2365, 1762, 1683, 1522, 1507, 1450,
1302, 1162, 1102, 913, 816, 748, 697, 555, 532. HRMS (ESI) m/z:
[M + H]+ Calcd for C24H24NO4S 422.1421; found 422.1418.
4-Nitro-N-((5-oxo-4,4-diphenyltetrahydrofuran-2-yl)methyl)-
benzenesulfonamide (2e-N7). Synthesized from 1e. Purified by silica
gel column chromatography (the eluent was petroleum ether/EtOAc
1
white solid (40.7 mg, 42%). mp 203.5−204.3 °C. H NMR (400
MHz, CDCl3): δ 7.99 (d, J = 7.6 Hz, 4H), 7.85 (d, J = 7.6 Hz, 1H),
7.70 (t, J = 7.6 Hz, 1H), 7.58−7.51 (m, 2H), 7.35 (d, J = 8.0 Hz, 4H),
4.28 (d, J = 16.0 Hz, 1H), 4.13 (d, J = 16.0 Hz, 1H), 2.45 (s, 6H),
1.53 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3): δ 168.7, 151.2,
145.1, 136.7, 134.3, 129.8, 129.5, 128.9, 126.2, 125.9, 121.9, 86.3,
56.3, 23.5, 21.7. IR νmax (cm−1): 3070, 2936, 1770, 1684, 1598, 1395,
1381, 1295, 1160, 1070, 1058, 865, 772, 743, 660, 551. HRMS (ESI)
m/z: [M + Na]+ Calcd for C24H23NNaO6S2 508.0859; found
508.0866.
4-Methyl-N-((1-oxo-1,3-dihydronaphtho[1,2-c]furan-3-yl)-
methyl)-N-tosylbenzenesulfonamide (4g). Synthesized from 3g
according to the procedure B. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
1
1:1) as a white solid (44.0 mg, 40%). mp 106.2−107.0 °C. H NMR
(400 MHz, CD3OD): δ 8.38 (d, J = 8.8 Hz, 1H), 8.12 (d, J = 8.8 Hz,
1H), 7.50−7.19 (m, 13H), 4.43 (ddd, J = 10.0, 8.0, 4.8 Hz, 1H), 3.88
(dd, J = 12.8, 2.8 Hz, 1H), 3.65 (dd, J = 12.8, 4.8 Hz, 1H), 3.04 (dd, J
= 13.2, 5.2 Hz, 1H), 2.86 (dd, J = 13.2, 10.8 Hz, 1H). 13C {1H} NMR
(100 MHz, CD3OD): δ 177.8, 142.4, 139.7, 128.4, 128.3, 127.9,
127.8, 127.4, 127.3, 127.1, 127.1, 126.6, 123.7, 78.0, 61.8, 58.0, 38.0.
IR νmax (cm−1): 3250, 2968, 2873, 2460, 1770, 1595, 1495, 1455,
1440, 1426, 1350, 1268, 1100, 1035, 826, 703, 680, 551. HRMS (ESI)
m/z: [M + H]+ Calcd for C23H21N2O6S 453.1115; found 453.1107.
Gram-Scale Synthesis of Compound 2q and Recovered
Experiment of Catalyst. To a 100 mL flask were added 1q (1.26 g,
5 mmol), I11 (132 mg, 0.5 mmol), HNTs2 (2.44 g, 7.5 mmol), and
mCPBA (1.78 g, 8.75 mmol, 85 wt %) in CH3CN (50 mL). The
mixture was stirred at room temperature for 5 h. After completion, the
mixture was quenched with an aqueous solution of NaOH (2 mol/L).
The mixture was extracted with EtOAc (50 mL × 3). The combined
organic phase was washed with brine, dried over Na2SO4, filtered, and
concentrated under vacuum. The residue was purified by flash
chromatography on silica gel (PE/EtOAc = 6:1) to give the
compound 2q as a white solid (2.00 g, 70%), byproduct 2q′ as a
yellow solid (120 mg, 9%), and catalyst I11 (63 mg, 48%) was
recovered as a yellow solid. The recovered catalyst also can catalyze
the same reaction under standard conditions and gave the same result
(2q, 65%).
1
white solid (39.6 mg, 38%). mp 217.3−218.5 °C. H NMR (400
MHz, CDCl3): δ 8.21 (d, J = 7.2 Hz, 1H), 8.16 (d, J = 8.0 Hz, 4H),
8.05 (dd, J = 14.8, 8.0 Hz, 2H), 7.88 (d, J = 8.4 Hz, 1H), 7.82−7.75
(m, 2H), 7.44 (d, J = 7.6 Hz, 4H), 6.25 (d, J = 9.2 Hz, 1H), 4.39 (d, J
= 16.0 Hz, 1H), 4.01 (dd, J = 16.0, 9.6 Hz, 1H), 2.50 (s, 6H). 13C
{1H} NMR (100 MHz, CDCl3): δ 169.8, 145.8, 145.4, 136.3, 131.3,
129.7, 129.6, 129.3, 129.1, 128.9, 128.4, 126.9, 124.2, 124.0, 120.7,
80.5, 53.1, 21.6. IR νmax (cm−1): 3070, 2926, 2853, 1770, 1597, 1375,
1292, 1165, 1084, 1035, 818, 762, 723, 663, 552. HRMS (ESI) m/z:
[M + Na]+ Calcd for C27H23NNaO6S2 544.0859; found 544.0848.
4-Methoxy-N-((4-methoxyphenyl)sulfonyl)-N-((5-oxo-4,4-diphe-
nyltetrahydrofuran-2-yl)methyl)benzenesulfonamide (2e-N1). Syn-
thesized from 1e. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (92.3 mg,
76%). mp 217.9−218.5 °C. 1H NMR (400 MHz, CDCl3): δ 7.97 (d, J
= 8.8 Hz, 4H), 7.33 (ddd, J = 17.2, 13.2, 6.2 Hz, 6H), 7.25−7.16 (m,
4H), 6.96 (d, J = 8.8 Hz, 4H), 4.60 (dq, J = 10.2, 5.2 Hz, 1H), 4.14
(dd, J = 16.0, 6.4 Hz, 1H), 3.90−3.82 (s, 7H), 2.96 (dd, J = 13.2, 5.2
Hz, 1H), 2.74−2.63 (m, 1H). 13C {1H} NMR (100 MHz, CDCl3): δ
176.1, 164.0, 141.4, 139.5, 130.9, 130.6, 129.0, 128.4, 127.8, 127.7,
127.3, 127.2, 114.3, 75.3, 57.8, 55.8, 51.1, 41.0. IR νmax (cm−1): 3062,
2947, 2842, 2360, 1773, 1595, 1577, 1496, 1459, 1449, 1375, 1266,
1162, 1086, 1024, 835,806, 738, 697, 667, 556. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C31H29NNaO8S2 630.1227; found 630.1224.
N-((5-Oxo-4,4-diphenyltetrahydrofuran-2-yl)methyl)-N-(phenyl-
sulfonyl)benzenesulfonamide (2e-N3). Synthesized from 1e. Puri-
fied by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 4:1) as a white solid (106.0 mg, 90%). mp 87.7−88.4
°C. 1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 7.6 Hz, 4H), 7.64 (t,
J = 7.6 Hz, 2H), 7.53 (t, J = 7.6 Hz, 4H), 7.39−7.21 (m, 10H), 4.63
(dq, J = 10.4, 5.2 Hz, 1H), 4.20 (dd, J = 16.0, 6.4 Hz, 1H), 3.90 (dd, J
= 16.0, 4.8 Hz, 1H), 2.98 (dd, J = 13.2, 5.2 Hz, 1H), 2.70 (dd, J =
N-(2-Hydroxy-3-(9-(hydroxymethyl)-9H-fluoren-9-yl)propyl)-4-
methyl-N-tosylbenzenesulfonamide (5).11a To a 25 mL flask
equipped with a stir bar were added 2q (114 mg, 0.2 mmol) and
BH3·THF (10 mL, 1.0 M) under argon protected. The mixture was
stirred at room temperature for 1 h. After completion, MeOH was
added dropwise to quench the reaction. Then, the mixture was
concentrated under vacuum. The residue was purified by flash
chromatography on silica gel (DCM/MeOH = 15:1) to give the
1
compound 5 as a white solid (95 mg, 85%). mp 87.6−88.3 °C. H
5161
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NMR (400 MHz, CDCl3): δ 7.79 (dd, J = 7.2, 4.2 Hz, 2H), 7.71 (d, J
= 8.0 Hz, 4H), 7.54 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.43
(t, J = 7.6 Hz, 2H), 7.34 (dt, J = 6.6, 3.2 Hz, 2H), 7.24 (d, J = 8.4 Hz,
4H), 3.84 (s, 1H), 3.77 (d, J = 11.2 Hz, 1H), 3.65 (d, J = 11.2 Hz,
1H), 3.56 (dd, J = 15.6, 9.1 Hz, 1H), 3.32 (dd, J = 15.6, 3.0 Hz, 1H),
2.62−2.52 (m, 2H), 2.48−2.36(m, 7H),1.93 (dd, J = 14.4, 3.2 Hz,
1H).13C {1H} NMR (100 MHz, CDCl3): δ 148.3, 146.8, 145.0, 140.8,
140.3, 136.4, 129.6, 128.3, 128.0, 127.9, 127.5, 127.3, 124.7, 123.8,
120.4, 120.3, 69.3, 67.8, 55.0, 54.6, 40.1, 21.7. IR νmax (cm−1): 3560,
3425, 3075, 2926, 2863, 1597, 1494, 1477, 1448, 1371, 1166, 1085,
1053, 815, 738, 663, 552. HRMS (ESI) m/z: [M + Na]+ Calcd for
C31H31NNaO6S2 600.1485; found 600.1481.
5′-(Aminomethyl)-4′,5′-dihydro-2′H-spiro[fluorene-9,3′-furan]-
2′-one (6).31 To a 50 mL pressure flask were added 2q (300 mg, 0.52
mmol) and resorcinol (250 mg, 5.0 equiv). A solution of hydrogen
bromide in acetic acid (5 mL, 33 wt %) was dropwise added to the
pressure flask, which was heated in an oil bath at 85 °C for 24 h. After
completion, the acetic acid was removed under vacuum, and the
brown residue was dissolved in water (30 mL) and washed with ether
(30 mL × 3). To the aqueous phase was added excess saturated
sodium carbonate until pH > 7; then the mixture was extracted with
dichloromethane (30 mL × 3), washed with brine, dried over
Na2SO4, filtered, and concentrated under vacuum. The residue was
purified by flash chromatography on silica gel (DCM/MeOH =
20:1−2:1) to give the compound 6 as a yellowish solid (106 mg,
80%). mp 143.9−144.5 °C. 1H NMR (400 MHz, (CD3)2SO): δ 7.81
(dd, J = 17.6, 8.4 Hz, 3H), 7.59 (d, J = 7.2 Hz, 2H), 7.42−7.33 (m,
2H), 7.31 (s, 1H), 5.24 (s, 1H), 4.47 (s, 1H), 3.58 (d, J = 11.2 Hz,
1H), 3.31 (s, 2H), 2.354 (t, J = 11.6 Hz, 1H), 1.88 (d, J = 12.8 Hz,
1H). 13C {1H} NMR (100 MHz, (CD3)2SO): δ 170.4, 150.9, 150.6,
141.0, 140.8, 128.2, 128.1, 127.9, 127.8, 124.8, 124.0, 120.6, 120.3,
62.1, 57.4, 49.0, 42.5. IR νmax (cm−1): 2925, 2858, 1761, 1684, 1449,
1167, 970, 731, 619. HRMS (ESI) m/z: [M + Na]+ Calcd for
C17H15NNaO2 288.0995; found 288.0996.
3H), 1.55 (dd, J = 8.8, 6.8 Hz, 6H). 13C {1H} NMR (150 MHz,
CDCl3): δ 171.2, 171.2, 157.4, 157.3, 140.6, 140.6, 136.8, 136.6,
136.3, 136.3, 128.9, 128.8, 128.6, 128.5, 128.1, 128.1, 127.6, 127.6,
127.4, 127.4, 126.9, 126.9, 108.4, 107.9, 76.4, 76.0, 75.8, 75.7, 49.5,
49.4, 48.3, 48.3, 21.9, 21.8, 18.2, 18.1. IR νmax (cm−1): 3080, 3065,
3027, 2983, 2925, 2355, 2335, 1665, 1575, 1495, 1453, 1425, 1380,
1361, 1240, 1215, 1135, 1102, 1028, 1022, 817, 735, 698, 570, 460.
HRMS (ESI) m/z: [M + H]+ Calcd for C41H42IN2O4 753.2184;
found 753.2183.
General Procedures for Asymmetric Aminolactonization
Reaction. A 10 mL pyrex tube was charged with ArI*1 (11.3 mg, 15
mol %), HNTs2 (48.8 mg, 1.5 equiv), and mCPBA (35.5 mg, 1.75
equiv, 85 wt %) in PhCF3 (1 mL). After stirring at −10 °C for 15 min,
the substrate 1 (0.1 mmol, 1.0 equiv) was added. The mixture was
stirred for 60 h at −10 °C. After completed, the resulting mixture was
diluted with an aqueous NaOH (2 mol/L, 5 mL) and extracted with
EtOAc (15 mL × 3). The organic phase was washed with brine, dried
over Na2SO4, filtered, and concentrated under vacuum. The residue
was purified by flash column chromatography on silica gel (PE/
EtOAc = 10:1−1:1) to give the chiral aminolactonization products
2b*, 2d*, 2e*, and 2n*.
N-((4,4-Dimethyl-5-oxotetrahydrofuran-2-yl)methyl)-4-methyl-
N-tosylbenzenesulfonamide (2b*). White solid in 67% yield after 60
h. HPLC (Chiralpak IA3 column, hexane/i-PrOH = 90/10), flow rate
0.8 mL/min, λ = 214 nm, tR (minor) = 19.64 min, tR (major) = 27.79
min, 54% ee.
4-Methyl-N-((5-oxo-4,4-dipropyltetrahydrofuran-2-yl)methyl)-N-
tosylbenzenesulfonamide (2d*). White solid in 60% yield after 60 h.
HPLC (Chiralpak OD-H column, hexane/i-PrOH = 95/5), flow rate
0.8 mL/min, λ = 214 nm, tR (minor) = 19.67 min, tR (major) = 22.90
min, 30% ee.
4-Methyl-N-((5-oxo-4,4-diphenyltetrahydrofuran-2-yl)methyl)-
N-tosylbenzenesulfonamide (2e*). White solid in 89% yield after 60
h. HPLC (Chiralpak IA3 column, hexane/i-PrOH = 90/10), flow rate
0.8 mL/min, λ = 214 nm, tR (minor) = 31.86 min, tR (major) = 37.01
min, 88% ee.
4-Methyl-N-((1-oxo-2-oxaspiro[4.5]decan-3-yl)methyl)-N-tosyl-
benzenesulfonamide (2n*). White solid in 60% yield after 60 h.
HPLC (Chiralpak IA3 column, hexane/i-PrOH = 90/10), flow rate
0.8 mL/min, λ = 214 nm, tR (minor) = 26.80 min, tR (major) = 30.36
min, 65% ee.
5′-((Diethylamino)methyl)-4′,5′-dihydro-2′H-spiro[fluorene-9,3′-
furan]-2′-one (7).10b To a 50 mL flask were added 6 (106 mg, 0.4
mmol), potassium carbonate (500 mg, 3.6 mmol), and iodoethane (5
mL, excessive) in tetrahydrofuran (20 mL). The reaction mixture was
heated in an oil bath under reflux at 69 °C for 24 h. After completion,
the mixture was concentrated under vacuum. The residue was purified
by flash chromatography on silica gel (DCM/MeOH = 30:1−15:1) to
1
give the compound 7 as a yellow oil (120 mg, 93%). H NMR (400
MHz, (CD3)2SO): δ 7.94−7.87 (m, 2H), 7.68 (dd, J = 19.6, 7.2 Hz,
2H), 7.46 (t, J = 7.2 Hz, 2H), 7.38 (dt, J = 14.4, 7.2 Hz, 2H), 5.30−
5.16 (m, 1H), 2.89 (t, J = 10.0 Hz, 2H), 2.84−2.76 (m, 1H), 2.70−
2.56 (m, 5H), 1.03 (t, J = 7.2 Hz, 6H). 13C {1H} NMR (100 MHz,
(CD3)2SO): δ 177.0, 146.7, 146.1, 141.4, 140.4, 129.1, 129.0, 128.6,
128.6, 124.4, 123.7, 121.0, 120.8, 78.1, 58.8, 57.2, 47.8, 38.5, 12.4. IR
νmax (cm−1): 2970, 2930, 2816, 1762, 1557, 1522, 1448, 1170, 1057,
1035, 967, 753, 732. HRMS (ESI) m/z: [M + H]+ Calcd for
C21H24NO2 322.1802; found 322.1795.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00074.
Tables of detailed reaction condition screening, picture
of kinetic experiments, crystal data, NMR spectra (PDF)
(2R,2′R)-2,2′-((2-Iodo-5-methyl-1,3-phenylene)bis(oxy))bis(N,N-
dibenzylpropanamide) (ArI*1).17b Step one: To a solution of
(2R,2′R)-2,2′-((2-iodo-5-methyl-1,3-phenylene)bis(oxy))dipropionic
acid (0.5 g, 1.27 mmol) in DCM (20 mL) was added oxalyl chloride
(1.0 mL, 10 mmol) dropwise. Then, N,N-dimethylformamide (2
drops) was added. After stirring for 2 h, the mixture was concentrated
under vacuum. Step two: To a flask were added dibenzylamine (1.0
mL, 5 mmol), Et3N (1 mL, 7 mmol), and DCM (20 mL). Then, the
product of the step one (in 10 mL DCM) was dropwise added to the
reaction mixture at 0 °C. After stirring for 4 h at room temperature,
the mixture was acidified with an aqueous solution of HCl (2 mol/L).
The mixture was extracted with dichloromethane (20 mL × 3). The
combined organic phase was washed with brine, dried over Na2SO4,
filtered, and concentrated under vacuum. The residue was purified by
flash chromatography on silica gel (PE/EtOAc = 5:1) to give the
compound ArI*1 as a white solid (694 mg, 73%). mp 173.5−174.8
°C. 1H NMR (600 MHz, CDCl3): δ 7.18−7.10 (m, 8H), 7.08 (dd, J =
7.2, 4.0 Hz, 4H), 7.00−6.88 (m, 8H), 6.23 (d, J = 5.2 Hz, 2H), 4.95
(dq, J = 9.6, 6.8 Hz, 2H), 4.67−4.33 (m, 8H), 2.11 (d, J = 4.8 Hz,
Accession Codes
CCDC 2050572, 2050577, 2050580, 2050581, 2060874,
2063255, and 2063265 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
Wei He − Department of Chemistry, School of Pharmacy, The
Fourth Military Medical University, Xi’an 710032, China;
orcid.org/0000-0002-6703-6855; Email: weihechem@
fmmu.edu.cn
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J. Org. Chem. 2021, 86, 5152−5165

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(5) (a) Sharpless, K. B.; Chong, A. O.; Oshima, K. Osmium-
Catalyzed Vicinal Oxyamination of Olefins by Chloramine-T. J. Org.
Chem. 1976, 41, 177−179. (b) Li, G.; Chang, H.-T.; Sharpless, K. B.
Catalytic Asymmetric Aminohydroxylation (AA) of Olefins. Angew.
Chem., Int. Ed. Engl. 1996, 35, 451−454. (c) Donohoe, T. J.;
Churchill, G. H.; Wheelhouse, K. M. P.; Glossop, P. A. Stereoselective
Synthesis of Pyrrolidines: Catalytic Oxidative Cyclizations Mediated
by Osmium. Angew. Chem., Int. Ed. 2006, 45, 8025−8028.
(d) Masruri; Willis, A. C.; McLeod, M. D. Osmium-Catalyzed Vicinal
Oxyamination of Alkenes by N-(4-Toluenesulfonyloxy)carbamates. J.
Org. Chem. 2012, 77, 8480−8491.
(6) (a) Nakafuku, K. M.; Fosu, S. C.; Nagib, D. A. Catalytic Alkene
Difunctionalization via Imidate Radicals. J. Am. Chem. Soc. 2018, 140,
11202−11205. (b) Lei, H.; Conway, J. H.; Cook, C. C.; Rovis, T.
Ligand Controlled Ir-Catalyzed Regiodivergent Oxyamination of
Unactivated Alkenes. J. Am. Chem. Soc. 2019, 141, 11864−11869.
(7) (a) Levites-Agababa, E.; Menhaji, E.; Perlson, L. N.; Rojas, C. M.
Amidoglycosylation via Metal-Catalyzed Internal Nitrogen Atom
Delivery. Org. Lett. 2002, 4, 863−865. (b) Beaumont, S.; Pons, V.;
Retailleau, P.; Dodd, R. H.; Dauban, P. Catalytic Oxyamidation of
Indoles. Angew. Chem., Int. Ed. 2010, 49, 1634−1637.
Authors
Lu-Wen Zhang − Department of Chemistry, School of
Pharmacy, The Fourth Military Medical University, Xi’an
710032, China
Xiao-Jun Deng − Department of Chemistry, School of
Pharmacy, The Fourth Military Medical University, Xi’an
710032, China
Dong-Xu Zhang − Department of Medicinal Chemistry,
School of Pharmacy, The Fourth Military Medical University,
Xi’an 710032, China
Qin-Qin Tian − Department of Chemistry, School of
Pharmacy, The Fourth Military Medical University, Xi’an
710032, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00074
Notes
The authors declare no competing financial interest.
(8) Sun, X.; Li, X.; Song, S.; Zhu, Y.; Liang, Y.-F.; Jiao, N. Mn-
Catalyzed Highly Efficient Aerobic Oxidative Hydroxyazidation of
Olefins: A Direct Approach to β-Azido Alcohols. J. Am. Chem. Soc.
2015, 137, 6059−6066.
ACKNOWLEDGMENTS
■
This work was supported by the Shaanxi Province Key
Research and Development Program (grant no. 2019ZDLSF-
03-03) and the National Science and Technology Major
Project of China Key New Drug Creation and Development
Program (project no. 2014ZX09J14104-06C). We also would
like to give great thanks to professor Sheng-Yong Zhang and
professor Zhi-Xiang Yu for valuable discussions.
(9) (a) Schmidt, V. A.; Alexanian, E. J. Metal-Free Oxyaminations of
Alkenes Using Hydroxamic Acids. J. Am. Chem. Soc. 2011, 133,
11402−11405. (b) Wang, T.; Jiao, N. TEMPO-catalyzed Aerobic
Oxygenation and Nitrogenation of Olefins via C=C Double-Bond
Cleavage. J. Am. Chem. Soc. 2013, 135, 11692−11695. (c) Yang, B.;
Lu, Z. Visible-Light-Promoted Metal-Free Aerobic Hydroxyazidation
of Alkenes. ACS Catal. 2017, 7, 8362−8365. (d) He, J.; Dong, J.; Su,
L.; Wu, S.; Liu, L.; Yin, S.-F.; Zhou, Y. Selective Oxidative Cleavage of
3-Methylindoles with Primary Amines Affording Quinazolinones. Org.
Lett. 2020, 22, 2522−2526.
REFERENCES
■
(1) (a) O’Brien, P. Sharpless Asymmetric Aminohydroxylation:
Scope, Limitations, and Use in Synthesis. Angew. Chem., Int. Ed. 1999,
38, 326−329. (b) Donohoe, T. J.; Callens, C. K. A.; Flores, A.; Lacy,
A. R.; Rathi, A. H. Recent Developments in Methodology for the
Direct Oxyamination of Olefins. Chem. - Eur. J. 2011, 17, 58−76.
(2) (a) Wu, F.; Ariyarathna, J. P.; Alom, N.-E.; Kaur, N.; Li, W.
Oxyamination of Unactivated Alkenes with Electron-Rich Amines and
Acids via a Catalytic Triiodide Intermediate. Org. Lett. 2020, 22, 884−
890. (b) Li, Z.-L.; Fang, G.-C.; Gu, Q.-S.; Liu, X.-Y. Recent Advances
in Copper-Catalysed Radical-Involved Asymmetric 1,2-Difunctional-
ization of Alkenes. Chem. Soc. Rev. 2020, 49, 32−48. (c) Fuller, P. H.;
Kim, J.-W.; Chemler, S. R. Copper Catalyzed Enantioselective
Intramolecular Aminooxygenation of Alkenes. J. Am. Chem. Soc.
2008, 130, 17638−17639. (d) Chemler, S. R.; Karyakarte, S. D.;
Khoder, Z. M. Stereoselective and Regioselective Synthesis of
Heterocycles via Copper-Catalyzed Additions of Amine Derivatives
and Alcohols to Alkenes. J. Org. Chem. 2017, 82, 11311−11325.
(e) Ariyarathna, J. P.; Wu, F.; Colombo, S. K.; Hillary, C. M.; Li, W.
Aerobic Catalytic Features in Photoredox- and Copper-Catalyzed
Iodolactonization Reactions. Org. Lett. 2018, 20, 6462−6466.
(3) (a) Alexanian, E. J.; Lee, C.; Sorensen, E. J. Palladium-Catalyzed
Ring-Forming Aminoacetoxylation of Alkenes. J. Am. Chem. Soc.
2005, 127, 7690−7691. (b) McDonald, R. I.; Liu, G.; Stahl, S. S.
Palladium(II)-Catalyzed Alkene Functionalization via Nucleopallada-
tion: Stereochemical Pathways and Enantioslective Catalytic
Applications. Chem. Rev. 2011, 111, 2981−3019. (c) Qi, X.; Chen,
C.; Hou, C.; Fu, L.; Chen, P.; Liu, G. Enantioselective Pd(II)-
Catalyzed Intramolecular Oxidative 6-endo Aminoacetoxylation of
Unactivated Alkenes. J. Am. Chem. Soc. 2018, 140, 7415−7419.
(4) (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Iron-Catalyzed
Reactions in Organic Synthesis. Chem. Rev. 2004, 104, 6217−6254.
(b) Williamson, K. S.; Yoon, T. P. Iron-Catalyzed Aminohydrox-
ylation of Olefins. J. Am. Chem. Soc. 2010, 132, 4570−4571. (c) Liu,
G.-S.; Zhang, Y.-Q.; Yuan, Y.-A.; Xu, H. Iron(II)-Catalyzed
Intramolecular Aminohydroxylation of Olefins with Functionalized
Hydroxylamines. J. Am. Chem. Soc. 2013, 135, 3343−3346.
(10) (a) Blaskó, G.; Gula, D. J.; Shamma, M. The Phthalideisoqui-
noline Alkaloids. J. Nat. Prod. 1982, 45, 105−122. (b) Fytas, G.;
Foscolos, G. B.; Vyzas, A.; Garoufalias, S.; Fialip, J.; Marty, H.
́
Aminolactones Fluoreniques. Eur. J. Med. Chem. 1988, 23, 483−485.
(c) Kaiser, C.; Spagnuolo, C. J.; Adams, T. J.; Audia, V. H.; Dupont,
A. C.; Hatoum, H.; Lowe, V. C.; Prosser, J. C.; Sturm, B. L.; Noronha-
Blob, L. Synthesis and Antimuscarinic Properties of Some N-
Substituted 5-(Aminomethyl)-3,3-diphenyl-2(3H)-furanones. J. Med.
Chem. 1992, 35, 4415−4424. (d) Bös, M.; Stadler, H.; Wichmann, J.;
Jenck, F.; Martin, J. R.; Moreau, J.-L.; Sleight, A. J. Syntheses of O-
Methylasparvenone-Derived Serotonin-Receptor Antagonists. Helv.
Chim. Acta 1998, 81, 525−538. (e) Sugiyama, T.; Kittaka, A.;
Takayama, H.; Tomioka, M.; Ida, Y.; Kuroda, R. Aggregation of
RecA-Derived Peptides on Single-Stranded Oligonucleotides Trig-
gered by Schiff Base-Mediated Crosslinking. Bioorg. Med. Chem. Lett.
2003, 13, 2847−2851. (f) Huang, X.-H.; Zhu, Y.; Guan, X.-L.; Tian,
K.; Guo, J.-M.; Wang, H.-B.; Fu, G.-M. A Novel Antioxidant
Isobenzofuranone Derivative from Fungus Cephalosporium
sp.AL031. Molecules 2012, 17, 4219−4224.
(11) (a) DeBernardis, J. F.; Arendsen, D. L.; Kyncl, J. J.; Kerkman,
D. J. Conformationally Defined Adrenergic Agents.4. l-
(Aminomethyl)phthalans: Synthesis and Pharmacological Conse-
quences of the Phthalan Ring Oxygen Atom. J. Med. Chem. 1987,
30, 178−184. (b) Kitagawa, O.; Hanano, T.; Tanabe, K.; Shiro, M.;
Taguchi, T. Enantioselective Halocyclization Reaction Using a Chiral
Titanium Complex. J. Chem. Soc., Chem. Commun. 1992, 1005−1007.
(c) Bergmeier, S. C. The Synthesis of Vicinal Amino Alcohols.
Tetrahedron 2000, 56, 2561−2576.
(12) (a) Karila, D.; Leman, L.; Dodd, R. H. Copper-Catalyzed
Iminoiodane-Mediated Aminolactonization of Olefins: Application to
the Synthesis of 5,5-Disubstituted Butyrolactones. Org. Lett. 2011, 13,
5830−5833. (b) Hajra, S.; Akhtar, S. M. S.; Aziz, S. M. Catalytic
Asymmetric Aminolactonization of 1,2-Disubstituted Alkenoic Acid
Esters: Efficient Construction of Aminolactones with an All-Carbon
5163
https://doi.org/10.1021/acs.joc.1c00074
J. Org. Chem. 2021, 86, 5152−5165

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Quaternary Stereo-Centre. Chem. Commun. 2014, 50, 6913−6916.
(c) Zhu, R.; Buchwald, S. L. Versatile Enantioselective Synthesis of
Functionalized Lactones via Copper-Catalyzed Radical Oxyfunction-
alization of Alkenes. J. Am. Chem. Soc. 2015, 137, 8069−8077.
(d) Hemric, B. N.; Shen, K.; Wang, Q. Copper-Catalyzed Amino
Lactonization and Amino Oxygenation of Alkenes Using O-
Benzoylhydroxylamines. J. Am. Chem. Soc. 2016, 138, 5813−5816.
(e) Xie, J.; Wang, Y.-W.; Qi, L.-W.; Zhang, B. Access to Aminated
Saturated Oxygen Heterocycles via Copper-Catalyzed Aminooxyge-
nation of Alkenes. Org. Lett. 2017, 19, 1148−1151. (f) Wu, F.;
Stewart, S.; Ariyarathna, J. P.; Li, W. Aerobic Copper-Catalyzed
Alkene Oxyamination for Amino Lactone Synthesis. ACS Catal. 2018,
8, 1921−1925.
(13) (a) Wirth, T. Hypervalent Iodine Chemistry in Synthesis:
Scope and New Directions. Angew. Chem., Int. Ed. 2005, 44, 3656−
3665. (b) Zhdankin, V. V.; Stang, P. J. Chemistry of Polyvalent
Iodine. Chem. Rev. 2008, 108, 5299−5358. (c) Merritt, E. A.;
Olofsson, B. Diaryliodonium Salts: A Journey from Obscurity to
Fame. Angew. Chem., Int. Ed. 2009, 48, 9052−9070.
Versatile Entry to Hydroxy Lactams. J. Am. Chem. Soc. 2010, 132,
1188−1189. (c) Farid, U.; Wirth, T. Highly Stereoselective Metal-
Free Oxyaminations Using Chiral Hypervalent Iodine Reagents.
Angew. Chem., Int. Ed. 2012, 51, 3462−3465.
(20) Haupt, J. D.; Berger, M.; Waldvogel, S. R. Electrochemical
Fluorocyclization of N-Allylcarboxamides to 2-Oxazolines by Hyper-
valent Iodine Mediator. Org. Lett. 2019, 21, 242−245.
(21) (a) Pandey, C. B.; Azaz, T.; Verma, R. S.; Mishra, M.; Jat, J. L.;
Tiwari, B. Stereoselective Oxidative Rearrangement of Disubstituted
Unactivated Alkenes Using Hypervalent Iodine(III) Reagent. J. Org.
Chem. 2020, 85, 10175−10181. (b) Shimogaki, M.; Fujita, M.;
Sugimura, T. Metal-Free Enantioselective Oxidative Arylation of
Alkenes: Hypervalent-Iodine-Promoted Oxidative C−C Bond For-
mation. Angew. Chem., Int. Ed. 2016, 55, 15797−15801.
(22) (a) Braddock, D. C.; Cansell, G.; Hermitage, S. A. Ortho-
Substituted Iodobenzenes as Novel Organocatalysts for Bromination
of Alkenes. Chem. Commun. 2006, 2483−2485. (b) Liu, H.; Tan, C.-
H. Iodobenzene-Catalysed Iodolactonisation Using Sodium Perborate
Monohydrate as Oxidant. Tetrahedron Lett. 2007, 48, 8220−8222.
(c) Woerly, E. M.; Banik, S. M.; Jacobsen, E. N. Enantioselective,
Catalytic Fluorolactonization Reactions with a Nucleophilic Fluoride
Source. J. Am. Chem. Soc. 2016, 138, 13858−13861. (d) Xing, L.;
Zhang, Y.; Zhang, Y.; Ai, Z.; Li, X.; Du, Y.; Deng, J.; Zhao, K.
Regioselective Chlorolactonization of Styrene-Type Carboxylic Esters
and Amides via PhICl2-Mediated Oxidative C−O/C−Cl Bond
Formations. J. Org. Chem. 2019, 84, 13832−13840. (e) Xing, L.;
Zhang, Y.; Li, B.; Du, Y. Synthesis of 4-Chloroisocoumarins via
Intramolecular Halolactonization of o-Alkynylbenzoates: PhICl2-
Mediated C−O/C−Cl Bond Formation. Org. Lett. 2019, 21, 1989−
1993.
(23) (a) Yan, J.; Wang, H.; Yang, Z.; He, Y. An Efficient Catalytic
Sulfonyloxylactonization of Alkenoic Acids Using Hypervalent
Iodine(III) Reagent. Synlett 2009, 2009, 2669−2672. (b) Fujita,
M.; Yoshida, Y.; Miyata, K.; Wakisaka, A.; Sugimura, T.
Enantiodifferentiating endo-Selective Oxylactonization of ortho-Alk-
1-enylbenzoate with a Lactate-Derived Aryl-λ3-Iodane. Angew. Chem.,
Int. Ed. 2010, 49, 7068−7071. (c) Shimogaki, M.; Fujita, M.;
Sugimura, T. Enantioselective Oxidation of Alkenylbenzoates
Catalyzed by Chiral Hypervalent Iodine(III) to Yield 4-Hydrox-
yisochroman-1-ones. Eur. J. Org. Chem. 2013, 2013, 7128−7138.
(d) Takesue, T.; Fujita, M.; Sugimura, T.; Akutsu, H. A Series of Two
Oxidation Reactions of ortho-Alkenylbenzamide with Hypervalent
Iodine(III): A Concise Entry into (3R,4R)-4-Hydroxymellein and
(3R,4R)-4-Hydroxy-6-methoxymellein. Org. Lett. 2014, 16, 4634−
4637. (e) Gelis, C.; Dumoulin, A.; Bekkaye, M.; Neuville, L.; Masson,
G. Chiral Hypervalent Iodine(III) Catalyst Promotes Highly
Enantioselective Sulfonyl- and Phosphoryl-oxylactonizations. Org.
Lett. 2017, 19, 278−281.
(24) (a) Dohi, T.; Maruyama, A.; Takenaga, N.; Senami, K.;
Minamitsuji, Y.; Fujioka, H.; Caemmerer, S. B.; Kita, Y. A Chiral
Hypervalent Iodine(III) Reagent for Enantioselective Dearomatiza-
tion of Phenols. Angew. Chem., Int. Ed. 2008, 47, 3787−3790.
(b) Uyanik, M.; Yasui, T.; Ishihara, K. Enantioselective Kita Oxidative
Spirolactonization Catalyzed by In Situ Generated Chiral Hypervalent
Iodine(III) Species. Angew. Chem., Int. Ed. 2010, 49, 2175−2177.
(c) Uyanik, M.; Yasui, T.; Ishihara, K. Hydrogen Bonding and
Alcohol Effects in Asymmetric Hypervalent Iodine Catalysis:
Enantioselective Oxidative Dearomatization of Phenols. Angew.
Chem., Int. Ed. 2013, 52, 9215−9218.
(14) (a) Li, X.; Chen, P.; Liu, G. Recent Advances in Hypervalent
Iodine(III)-Catalyzed Functionalization of Alkenes. Beilstein J. Org.
Chem. 2018, 14, 1813−1825. (b) Parra, A. Chiral Hypervalent
Iodines: Active Players in Asymmetric Synthesis. Chem. Rev. 2019,
̀
119, 12033−12088. (c) Flores, A.; Cots, E.; Berges, J.; Muniz, K.
̃
Enantioselective Iodine(I/III) Catalysis in Organic Synthesis. Adv.
Synth. Catal. 2019, 361, 2−25.
(15) (a) Röben, C.; Souto, J. A.; González, Y.; Lishchynskyi, A.;
Mun
Angew. Chem., Int. Ed. 2011, 50, 9478−9482. (b) Souto, J. A.;
González, Y.; Iglesias, A.; Zian, D.; Lishchynskyi, A.; Muniz, K.
̃
iz, K. Enantioselective Metal-Free Diamination of Styrenes.
̃
Iodine(III)-Promoted Intermolecular Diamination of Alkenes. Chem. -
Asian J. 2012, 7, 1103−1111. (c) Souto, J. A.; Martínez, C.; Velilla, I.;
Muniz, K. Defined Hypervalent Iodine(III) Reagents Incorporating
̃
Transferable Nitrogen Groups: Nucleophilic Amination through
Electrophilic Activation. Angew. Chem., Int. Ed. 2013, 52, 1324−
1328. (d) Muniz, K.; Barreiro, L.; Romero, R. M.; Martínez, C.
̃
Catalytic Asymmetric Diamination of Styrenes. J. Am. Chem. Soc.
2017, 139, 4354−4357. (e) Muniz, K. Promoting Intermolecular C−
̃
N Bond Formation under the Auspices of Iodine(III). Acc. Chem. Res.
2018, 51, 1507−1519.
(16) (a) Zhong, W.; Liu, S.; Yang, J.; Meng, X.; Li, Z. Metal-Free,
Organocatalytic Syn Diacetoxylation of Alkenes. Org. Lett. 2012, 14,
3336−3339. (b) Haubenreisser, S.; Wöste, T. H.; Martínez, C.;
Ishihara, K.; Muniz, K. Structurally Defined Molecular Hypervalent
̃
Iodine Catalysts for Intermolecular Enantioselective Reactions. Angew.
Chem., Int. Ed. 2016, 55, 413−417.
(17) (a) Banik, S. M.; Medley, J. W.; Jacobsen, E. N. Catalytic,
Asymmetric Difluorination of Alkenes to Generate Difluoromethy-
lated Stereocenters. Science 2016, 353, 51−54. (b) Sarie, J. C.;
Thiehoff, C.; Neufeld, J.; Daniliuc, C. G.; Gilmour, R. Enantiose-
lective Synthesis of 3-Fluorochromanes via Iodine(I)/Iodine(III)
Catalysis. Angew. Chem., Int. Ed. 2020, 59, 15069−15075. (c) Levin,
M. D.; Ovian, J. M.; Read, J. A.; Sigman, M. S.; Jacobsen, E. N.
Catalytic Enantioselective Synthesis of Difluorinated Alkyl Bromides.
J. Am. Chem. Soc. 2020, 142, 14831−14837.
(18) (a) Kitamura, T.; Miyake, A.; Muta, K.; Oyamada, J.
Hypervalent Iodine/HF Reagents for the Synthesis of 3-Fluoropyrro-
lidines. J. Org. Chem. 2017, 82, 11721−11726. (b) Mennie, K. M.;
Banik, S. M.; Reichert, E. C.; Jacobsen, E. N. Catalytic Diastereo- and
Enantioselective Fluoroamination of Alkenes. J. Am. Chem. Soc. 2018,
(25) (a) Hussain, H.; Al-Harrasi, A.; Green, I. R.; Ahmed, I.; Abbas,
G.; Rehman, N. U. Meta-Chloroperbenzoic Acid (mCPBA): A
Versatile Reagent in Organic Synthesis. RSC Adv. 2014, 4, 12882−
12917. (b) Liu, G.-Q.; Li, L.; Duan, L.; Li, Y.-M. mCPBA-Mediated
Metal-Free Intramolecular Aminohydroxylation and Dioxygenation of
Unfunctionalized Olefins. RSC Adv. 2015, 5, 61137−61143.
(c) Deng, X.-J.; Zhang, L.-W.; Liu, H.-X.; Bai, Y.; He, W. mCPBA-
Mediated Dioxygenation of Unactivated Alkenes for the Synthesis of
5-Imino-2-tetrahydrofuranyl Methanol Derivatives. Tetrahedron Lett.
2020, 61, 152620.
140, 4797−4802. (c) Wang, Q.; Lubcke, M.; Biosca, M.; Hedberg,
̈
M.; Eriksson, L.; Himo, F.; Szabó, K. J. Enantioselective Construction
of Tertiary Fluoride Stereocenters by Organocatalytic Fluorocycliza-
tion. J. Am. Chem. Soc. 2020, 142, 20048−20057.
(19) (a) Lovick, H. M.; Michael, F. E. Metal-Free Highly
Regioselective Aminotrifluoroacetoxylation of Alkenes. J. Am. Chem.
Soc. 2010, 132, 1249−1251. (b) Wardrop, D. J.; Bowen, E. G.;
Forslund, R. E.; Sussman, A. D.; Weerasekera, S. L. Intramolecular
Oxamidation of Unsaturated O-Alkyl Hydroxamates: A Remarkably
5164
https://doi.org/10.1021/acs.joc.1c00074
J. Org. Chem. 2021, 86, 5152−5165

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(26) Deng, X.-J.; Liu, H.-X.; Zhang, L.-W.; Zhang, G.-Y.; Yu, Z.-X.;
He, W. Iodoarene-Catalyzed Oxyamination of Unactivated Alkenes to
Synthesize 5-Imino-2-tetrahydrofuranyl Methanamine Derivatives. J.
Org. Chem. 2021, 86, 235−253.
(27) Butt, S. E.; Das, M.; Sotiropoulos, J.-M.; Moran, W. J.
Computationally Assisted Mechanistic Investigation into Hypervalent
Iodine Catalysis: Cyclization of N-Allylbenzamide. J. Org. Chem.
2019, 84, 15605−15613.
(28) (a) Rao, W.-H.; Jiang, L.-L.; Liu, X.-M.; Chen, M.-J.; Chen, F.-
Y.; Jiang, X.; Zhao, J.-X.; Zou, G.-D.; Zhou, Y.-Q.; Tang, L.
Copper(II)-Catalyzed Alkene Aminosulfonylation with Sodium
Sulfinates For the Synthesis of Sulfonylated Pyrrolidones. Org. Lett.
2019, 21, 2890−2893. (b) Moore, D. L.; Denton, A. E.; Kohinke, R.
M.; Craig, B. R.; Brenzovich, W. E. Silica Sulfuric Acid as a Highly
Efficient Catalyst for the Synthesis of Diarylacetic Acids. Synth.
Commun. 2016, 46, 604−612. (c) Raghavan, S. C.; Shivaprakash, N.
C.; Sindhu, S. N. Synthesis of Solution-Processable Poly(3,4
Propylenedioxythiophene) Nanobelts for Electrochromic Device
Applications. Opt. Mater. 2017, 73, 56−63. (d) Koder, R. L.;
Lichtenstein, B. R.; Cerda, J. F.; Miller, A.; Dutton, P. L. A Flavin
Analogue with Improved Solubility in Organic Solvents. Tetrahedron
Lett. 2007, 48, 5517−5520. (e) BouzBouz, S.; Boulard, L.; Cossy, J.
Ruthenium-Catalyzed Cross-Metathesis between Diallylsilanes and
Electron-Deficient Olefins. Org. Lett. 2007, 9, 3765−3768. (f) Innitzer,
A.; Brecker, L.; Mulzer, J. Functionalized Cyclobutanes via Heck
Cyclization. Org. Lett. 2007, 9, 4431−4434. (g) Moser, W. H.;
Hegedus, L. S. Photoreactions of γ,δ-Unsaturated Chromium Carbene
Complexes. J. Am. Chem. Soc. 1996, 118, 7873−7880. (h) Chen, Z.-
Y.; Wu, L.-Y.; Fang, H.-S.; Zhang, T.; Mao, Z.-F.; Zou, Y.; Zhang, X.-
J.; Yan, M. Intramolecular Hydroamidation of ortho-Vinyl Benzamides
Promoted by Potassium tert-Butoxide/N,N-Dimethylformamide. Adv.
Synth. Catal. 2017, 359, 3894−3899.
(29) (a) Jeong, Y.; Ban, J.; Lim, M.; Rhee, H. A Novel Synthesis of
N-Sulfonylformamidines from N-Sulfonyl-Sulfonamides. Synthesis
2018, 50, 1867−1874. (b) Martin, M. T.; Roschangar, F.; Eaddy, J.
F. Practical Acid-Catalyzed Acylation of Sulfonamides with Carboxylic
Acid Anhydrides. Tetrahedron Lett. 2003, 44, 5461−5463.
(30) Rudler, H.; Harris, P.; Parlier, A.; Cantagrel, F.; Denise, B.;
Bellassoued, M.; Vaissermann, J. Transition-Metal Catalyzed Syn-
thesis of δ-Hydroxy-γ-Lactones from Bis(trimethylsilyl) Ketene
Acetals and Allylic Acetates via γ-Unsaturated Carboxylic Acids.
Comments on the Formation of α-Cyclopropyl Carboxylic Acids. J.
Organomet. Chem. 2001, 624, 186−202.
(31) Haskell, B. E.; Bowlus, S. B. A New Synthesis of L-2-Amino-3-
oxalylaminopropionic Acid, the Lathyrus Sativus Neurotoxin. J. Org.
Chem. 1976, 41, 159−160.
5165
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J. Org. Chem. 2021, 86, 5152−5165