Hypervalent Iodine(III)-Mediated Tosyloxylation of 4-Hydroxycoumarins

Article abstract of DOI:10.1021/acs.joc.9b01323

An efficient approach was developed for synthesis of 3-tosyloxy-4-hydroxycoumarins under mild conditions by using Koser's reagents. The reaction tolerated various functional groups, and the products served as useful aromatic building blocks. Additionally, a plausible mechanism via iodonium ylide was proposed, and the oral anticoagulant Warfarin was synthesized in good yield.

Full text of DOI:10.1021/acs.joc.9b01323

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Article
Hypervalent Iodine(III) Mediated Tosyloxylation of 4-Hydroxycoumarins
Bowen Xu, Yiping Gao, Jianwei Han, Zejing Xing, Sihan Zhao, Ziyang Zhang, Runlin Ren, and Limin Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01323 • Publication Date (Web): 13 Jun 2019
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Hypervalent Iodine(III) Mediated Tosyloxylation of
4-Hydroxycoumarins
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Bowen Xu,† Yiping Gao,‡ Jianwei Han,*† Zejing Xing,† Sihan Zhao,† Ziyang Zhang,†
Runlin Ren,† and Limin Wang*†
†Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint
Research Center, Institute of Fine Chemicals, School of Chemistry and Molecular
Engineering, East China University of Science & Technology, 130 Meilong Road,
Shanghai, 200237, China
‡ Shanghai Xuhui Central Hospital, Shanghai 200031, P. R. China
Email: Jianwei Han – jianweihan@ecust.edu.cn; Limin Wang –
wanglimin@ecust.edu.cn
* Corresponding author
Abstract
An
efficient
approach
was
developed
for
synthesis
of
3-tosyloxy-4-hydroxycoumarins under mild conditions by using Koser’s reagents. The
reaction tolerated various functional groups and the products served as useful
aromatic building blocks. Additionally, a plausible mechanism via iodonium ylide was
proposed and the oral anticoagulant Warfarin was synthesized in good yield.
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Key words: Tosyloxylation, HTIB, Synthetic methods, Hypervalent iodine, Ylide.
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Introduction
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Recent years have witnessed a rapid growth in the field of hypervalent iodine
chemistry with exploring their novel reactivity in a diverse range of chemical
transformations.1 For example, hydroxy(tosyloxy)iodo]benzene (HTIB), which is
known as Koser’s reagent, is one of these useful reagents to perform
α-functionalization of ketones such as tosyloxylation, hydroxylation, and
acyloxylation.2 Following the seminal report that Koser et al. used HTIB to produce
corresponding α-tosyloxyketones from enolizable ketones and its first asymmetric
version by Wirth,3 much efforts were contributed to explore the activated aliphatic
ketones as well as the catalytic and enantioselective version of these reactions
(Scheme 1a).4 Recently, Legault et al. reported an elegant study on the mechanistic
insights of the α-tosyloxylation of ketones with computational method, in which
HTIB formed a novel iodonium intermediates as Lewis acids to enhance the
electrophilicity of carbonyl compounds.5 An experimental evidence supported this
mechanism in the α-tosyloxylation of enol esters by the same research group.6 As
such, HTIB involved tosyloxylations for transferring TsO-groups to the target
products would be ideal. Considering that arylsulfonates can serve as excellent
leaving groups for further coupling reactions, access to the aromatic compounds
bearing OTs group is a topic of much interest. The tosyloxylations of aromatic
substrates with HTIB is one highly desirable method. However, in sharp contrast,
tosyloxylations of aromatics or heterocyclic rings of this type have rarely been
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reported.7 In fact, as early as 1978, Kappe et al. reported the reaction of
4-hydroxycoumarin with (diacetoxyiodo)benzenes (DIB) to afford iodonium ylides in
good yields. Very recently, Panda et al. reported an efficient protocol for the synthesis
of coumestans, in which the iodine(III) reagents generated from iodobenzene in situ
by oxidants of mCPBA to afford the ylides.8 The iodonium ylides, also called as
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zwitterionic
iodonium
compounds
(ZICs),9
were
transformed
into
4-aryloxy-3-iodocoumarins via a variation of Smiles rearrangement, which further
gave coumestan derivatives (Scheme 1b).10
On the other hand, 4-hydroxycoumarins are important compounds in the synthesis
of bioactive molecules such as warfarin, acenocoumarol and phenprocoumon, which
are commonly prescribed as oral anticoagulants for prevention and treatment of
thromboembolic disorders.11 Additionally, sulfonyl group is a biologically active
pharmacophore as a part of several clinically used drugs.12 As a result, recently many
researchers have shown interested in sulfonyl-containing coumarin derivatives. For
examples, in 2016, Salar et al. reported a library of coumarin sulfonates by reacting
hydroxycoumarin with different substituted sulfonyl chlorides, in which eleven
compounds were demonstrated to have potential suppressive effect on production of
reactive oxygen species. Later, coumarin derived sulfonyl esters were also found to be
effective inhibitors of alkaline phosphatases.13 However, to the best of our knowledge,
there is no report concerning synthesis of 3-sulfonyl-4-hydroxycoumarins which
might also be potentially bioactive.
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Scheme 1. Tosyloxylation with HTIB.
Given our continued interest in the hypervalent iodine chemistry,14 we recently
synthesized iodonium salts that incorporated vicinal groups for exploring their unique
reactivity.14a When the reactivity pattern was attempted to prepare heterocyclic
iodonium salts bearing vicinal OTf groups, the tosyloxylation of 4-hydroxycoumarins
proceeded smoothly without phenyl migration by thermal rearrangement of iodonium
ylides. Herein we reported the detailed results in the preparation of 3-sulfonyl
substituted 4-hydroxycoumarins (Scheme 1c).
Results and Discussion
Preliminarily, treatment of 4-hydroxycoumarin (1a) with 0.4 equivalent HTIB (2a)
as model reaction in dichloromethane (DCM) at room temperature gave 40% yield of
3aa after 3 hours (Table 1, entry 1). In order to improve the yield of 3aa, we found
that the conversion of 1a afforded 3aa in 70% or 77% yield respectively when 1 or
1.2 equivalent HTIB was used. Further increasing the amount of 2a did not result in a
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better yield (Table 1, entries 2-4). Then, the effect of solvent was also examined and
the results were shown in Table 1. Reaction with toluene or MeCN as solvent
furnished lower yields at 46% and 52% respectively. Almost no reaction took place in
DMF and the reaction mixture changed into dark color at the moment when the
solvent was added (Table 1, entries 5-7). To our delight, the elevated temperature of
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o
35 C increased the yield to 85%, while higher temperature cannot result in a better
result (Table 1, entries 8-9). An investigation of reaction time indicated that the
reaction can finish in one hour (Table 1, entries 10-11).
Table 1. Reaction optimizationa
Entry
Solvent
DCM
DCM
DCM
DCM
Tol
Temp.(oC)
r.t.
Time(h)
Yield (%)
Eqv. of 2a
0.4
1
1
2
3
3
40
70
77
77
46
52
-
r.t.
3
1.2
2
3
r.t.
4
3
r.t.
5
1.2
1.2
1.2
1.2
1.2
1.2
1.2
3
r.t.
6
MeCN
DMF
DCM
DCM
DCM
DCM
3
r.t.
7
3
r.t.
8
3
85
86
85
36
35
9
3
reflux
35
10
11
1
0.5
35
a Reaction conditions: 1a (0.3 mmol), 2a and solvents (10 mL).
Next, the substrate scope of tosyloxylation of 4-hydroxycoumarin (1a) with various
Koser’s reagents was explored under the optimized conditions. As shown in Table 2,
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the 3-position tosyloxylation of 1a with Koser’s reagents including meta- or
para-halogen substituted aryl motifs afforded the corresponding products 3ab-3ae in
71-72% yields by the transfer of arylsulfonyl groups (Table 2, entries 1-4). A
moderate yield of 68% for 3af was achieved with 2f bearing phenyl group (Table 2,
entry 5). Koser’s reagent of 2g with 2,4-dinitroaryl unit resulted in the desired product
(3ag) in an acceptable yield of 46%. Regarding Koser’s reagents of 2h-2k contained
electron-withdrawing groups such as nitro-, trifluoromethoxy, trifluoromethyl and
nitrile groups, the reaction afforded 3ah-3ak in 54-75% yields (Table 2, entries 6-10).
Furthermore, when the Koser’s reagents of 2l-2m with electron-donating groups were
used in this protocol, the corresponding products of 3al and 3am were isolated in
excellent yields of 85% and 90% respectively, which suggested HTIBs bearing
electron-donating group favor this reaction (Table 2, entries 11-12). Of note, the
methylsulfonyl group can be transferred to give 3an in 43% yield when 2n was
employed. Additionally, hydroxyl-(phenyl)-iodanyl naphthalene-1-sulfonate (2l) was
also well tolerated in this reaction. It was worth to mention that 3ap with a camphor
sulfonate motif was afforded in 59% yield with this procedure (Table 2, entry 15).
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Table 2. Scope of diverse HTIB in tosyloxylationa
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Entry
1
R
Product
3ab
3ac
3ad
3ae
3af
Yield (%)
71
4-FC6H4
2
4-ClC6H4
4-BrC6H4
3-ClC6H4
C6H5
72
3
71
4
72
5
68
6
2,4-diNO2C6H4
4-OCF3C6H4
4-CF3C6H4
4-CNC6H4
4-NO2C6H4
4-tBuC6H4
4-OMeC6H4
Me
46
3ag
3ah
3ai
7
54
8
72
9
75
3aj
10
11
12
13
14
15
72
3ak
3al
85
90
3am
3an
3ao
3ap
43
2-Naphthalene
10-Camphor
59
55
a Reaction conditions: 1a (0.3 mmol), 2a (0.36 mmol) and DCM (10 mL) at 35 oC for 1 hour.
We successively examined the structural diversity of
a
variety of
4-hydroxycoumarin derivatives by changing the substituted groups on the molecular
skeleton. As shown in Table 3, both 6- and 7- position substituted
4-hydroxycoumarins with halogens, methyl and methoxy groups were well tolerated
in the tosyloxylation reaction, 3ba-3ja were furnished in 38-82% yields. Of note, the
reaction of 7-dimethylamine-4-hydroxycoumarin 1k with HTIB afforded the product
3ka in 64% yield. The compound of 3ka emitted strong fluorescence by irradiation of
ultraviolet light because of its D-π-A structure. Interestingly, methyl substituted
derivatives 1l-1m accomplished the tosyloxylated products in good yields of 77-80%.
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Moreover, the tosyloxylated benzo-4-hydroxycoumarin derivative 3na was
synthesized in 78% yield under the standard conditions with this protocol.
Furthermore, 4-hydroxy-1-methylquinolinone and 4-hydroxy-6-methyl-pyranone
were adopted in this reaction, the corresponding products of 3oa and 3pa15 were
obtained in 72% and 95% yields, respectively.
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Table 3. Scope of 4-hydroxycoumarin derivatives in 3-position tosyloxylationa
o
a
Reaction conditions: 1a (0.3 mmol), 2a (0.36 mmol) and DCM (10 mL) at 35 C for 1 hour.
b DCM (3 mL) was used.
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Next, to show the potential utility of target products, an attempt to convert the
tosyloxylation products into aromatic building blocks was described in Scheme 2. In
consideration of the benzenesulfonyl group as an excellent leaving group (LG), 3aa
was tried in the coupling reactions, however, 3aa did not exhibit any reactivity due to
the existence of ortho-carbonyl and hydroxyl groups. An alternative strategy to protect
the hydroxyl with trifluoromethanesulfonic anhydride (Tf2O) was employed to give
product 4 in 92% yield. Taking advantage of the leaving group of OTf, several
synthetic manipulations to transform 4 into functional molecules 5-8 were carried out.
Of note, biologically interesting molecule of vitamin E was directly coupled with 4 in
the presence of K2CO3 as base; the corresponding conjugated compound 5 was
formed in 42% yield. Additionally, the transition metal free coupling reaction of 4
under strong basic conditions using LiHMDS was attempted with diphenylphophane,
para-toluenethiol and furan, respectively, the corresponding products 6-8 were
obtained in 52-63% yields, which suggested 4 was an excellent coumarin-based motif
to prepare the related target molecules. For newly-formed benzenesulfonyl group as
leaving group (LG), further transformation of 6-8 with general coupling reactions of
Suzuki coupling and others, unfortunately, no positive result was achieved so far,
which may be due to the steric hindrance in the ortho-positions.
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Scheme 2. Versatility of 3aa in further transformations. a) Tf2O, Et3N, DCM. b)
K2CO3, Vitamin E, DMF, 100 oC. c) Furan, LiHDMs, Tol, r.t.. d)
o
o
4-Methylbenzenethiol, LiHDMs, Tol, 110 C. e) Ph2PH, LiHDMs, Tol, 110 C. DMF
= N,N-dimethylformamide, LiHDMs = Lithium bis(trimethylsilyl)amide, Tol =
toluene.
Control experiments were also performed to clarify the mechanism of this
transformation. Coumarin (9) and 4-tosyl substituted coumarin (10) were unable to
form the corresponding products under the standard conditions (Scheme 3a & 3b). A
low temperature reaction afforded the intermediate 11 in 83% isolated yield, which
was isolated and determined by NMR and HRMS.9 Furthermore, the iodonium ylide
11 can afford 3aa in 80% yield in the presence of TsOH (Scheme 3c). Interestingly,
the oral anticoagulant Warfarin was synthesized by using the intermediate of 11.
Warfarin 12 was synthesized in one step with 76% yield, which provides an
alternative way to afford this bioactive molecule without catalyst or addtional
promotors.
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As such, a plausible mechanism was proposed in scheme 4, of 4-hydroxycoumarin
in enol-keto tautomerism attacked the positive iodine center of Koser’s reagent to give
13, which formed iodonium ylide 11 by leaving of TsOH. 11 was easily transformed
into 3aa with the anion of OTs in the solvent.
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Scheme 3 Control experiments and synthesis of warfarin
Scheme 4 Plausible mechanism
Conclusion
In summary, we have developed an alternative method for 3-position tosyloxylation
of 4-hydroxycoumarin derivatives via sp2 C-H bond activation. The current approach
can tolerate various substrates under mild reaction condition without using
transition-metal catalyst. Furthermore, the oral anticoagulant Warfarin was
synthesized with this procedure, which demonstrated the potential applications of this
method in organic synthesis.
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Experimental Section
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1
General Information. (a) Methods: H, 13C spectra were recorded on a Bruker
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1
AVANCE 400 spectrometer, operating at 400 MHz for H NMR and 100 MHz for 13C
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NMR respectively. Chemical shifts (δ) are reported in ppm, and coupling constants (J)
are in Hertz (Hz). The following abbreviations were used to explain the multiplicities:
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad; Mass spectra
were in general recorded on a Waters LCT Premier XE spectrometer; Column
chromatography was performed with silica gel (200-300 mesh ASTM). All solvents
were dried and/or distilled by standard methods. (b) Materials: All solvents were
dried and/or distilled by standard methods. All reagents were purchased from
commercial
sources
and
used
without
further
purification.
The
[hydroxy(sulfonyloxy)iodo]arenes and the substituted 4-hydroxy-2H-chromen-2-one
16-18,4c
were synthesized according to the literature procedures
or commercially
available and were used as recevied. The preparation of all other materials is
described in detail below.
Procedure for Synthesis of 3-tosylated 4-hydroxy-2H-chromen-2-one:
To
a
50 ml round-bottomed flask was added the substituted
4-hydroxy-2H-chromen-2-one 1 (0.3 mmol) and [hydroxy(sulfonyloxy)iodo]arenes 2
o
(0.36 mmol). DCM (10 ml) was added and the mixture was stirred at 35 C under oil
bath for 1 hour. Then the solvent was evaporated under vacuum. The crude products
were purified using flash column chromatography on silica gel to afford the desired
product.
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4-Hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3aa). Following
the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2a (141 mg, 0.36 mmol)
8
9
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and DCM (10 mL) at 35 C for 1 h, after column chromatography on silica gel
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afforded 85 mg (85%) of 3aa as white solid. For a gram-scale experiment, following
the general procedure, the reaction of 1a (1.62 g, 10 mmol), 2a (4.7 g, 12 mmol) and
o
DCM (100 mL) at 35 C for 1 h, after column chromatography on silica gel afforded
2.72 g (82%) of 3aa as white solid. M.P.: 155-156 oC. 1H NMR (400 MHz, DMSO-d6)
δ 7.99 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.2 Hz, 2H), 7.72 (t, J = 7.8 Hz, 1H), 7.51 (d, J
= 8.2 Hz, 2H), 7.49 – 7.42 (m, 2H), 2.49 (s, 3H). A signal for OH-proton is not visible.
13C{1H} NMR (100 MHz, DMSO-d6) δ 157.8, 157.6, 151.0, 145.5, 132.8, 129.8,
128.4, 124.5, 124.0, 116.6, 116.5, 116.4, 21.2. HRMS m/z (ESI-TOF): calculated for
C16H12NaO6S [M+Na]+ 355.0252, found 355.0253.
4-Hydroxy-2-oxo-2H-chromen-3-yl 4-fluorobenzenesulfonate (3ab). Following the
general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2b (143 mg, 0.36 mmol) and
DCM (10 mL) at 35 oC for 1 h, after column chromatography on silica gel afforded 72
o
mg (71%) of 3ab as white solid. M.P.: 95-96 C. 1H NMR (400 MHz, DMSO-d6) δ
8.18 – 8.08 (m, 2H), 7.93 (dd, J = 7.7, 1.2 Hz, 1H), 7.64 – 7.58 (m, 1H), 7.55 – 7.44
(m, 2H), 7.35 (t, J = 8.0 Hz, 2H). A signal for OH-proton is not visible. 13C{1H} NMR
(100 MHz, DMSO-d6) δ 165.3(d, JC-F = 252 Hz), 160.5, 158.3, 151.4, 132.9, 132.1,
131.6(d, JC-F = 10 Hz), 124.4, 123.8, 118.6, 116.6, 116.4(d, JC-F = 23 Hz), 116.2.
HRMS m/z (ESI-TOF): calculated for C15H8O6SF [M-H]- 335.0026, found 335.0024.
4-Hydroxy-2-oxo-2H-chromen-3-yl 4-chlorobenzenesulfonate (3ac). Following the
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mg (72%) of 3ac as white solid. M.P.: 143-145 C. 1H NMR (400 MHz, DMSO-d6) δ
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8.04 – 7.97 (m, 2H), 7.94 (dd, J = 8.2, 1.3 Hz, 1H), 7.77 – 7.70 (m, 2H), 7.70 – 7.62
(m, 1H), 7.39 (t, J = 7.6 Hz, 2H). A signal for OH-proton is not visible. 13C{1H} NMR
(100 MHz, DMSO-d6) δ 158.8, 157.8, 151.1, 139.6, 134.9, 132.6, 130.3, 129.5, 124.3,
124.2, 117.1, 116.7, 116.4. HRMS m/z (ESI-TOF): calculated for C15H8O6SCl [M-H]-
350.9730, found 350.9736.
4-Hydroxy-2-oxo-2H-chromen-3-yl 4-bromobenzenesulfonate (3ad). Following
the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2d (164 mg, 0.36 mmol)
o
and DCM (10 mL) at 35 C for 1 h, after column chromatography on silica gel
o
afforded 84 mg (71%) of 3ad as white solid. M.P.: 154-155 C. 1H NMR (400 MHz,
DMSO-d6) δ 7.92 (t, J = 8.3 Hz, 3H), 7.85 (d, J = 8.3 Hz, 2H), 7.60 (t, J = 7.7 Hz, 1H),
7.39 – 7.28 (m, 2H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz,
DMSO-d6) δ 160.3, 158.2, 151.3, 135.9, 132.3, 130.2, 128.5, 126.7, 124.3, 123.9,
118.4, 116.6, 116.3. HRMS m/z (ESI-TOF): calculated for C15H8O6SBr [M-H]-
394.9225, found 394.9233.
4-Hydroxy-2-oxo-2H-chromen-3-yl 3-chlorobenzenesulfonate (3ae). Following the
general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2e (148 mg, 0.36 mmol) and
DCM (10 mL) at 35 oC for 1 h, after column chromatography on silica gel afforded 76
o
mg (72%) of 3ae as white solid. M.P.: 147-148 C. 1H NMR (400 MHz, DMSO-d6) δ
8.05 (s, 1H), 7.95 (dd, J = 6.3, 2.1 Hz, 2H), 7.90 (dd, J = 8.1, 1.1 Hz, 1H), 7.68 (dd, J
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= 15.4, 7.5 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H). A signal for OH-proton is not visible.
13C{1H} NMR (100 MHz, DMSO-d6) δ 158.6, 157.8, 151.1, 137.8, 134.6, 133.8,
132.7, 131.3, 127.8, 127.1, 124.3, 124.2, 116.7, 116.5. HRMS m/z (ESI-TOF):
calculated for C15H8O6SCl [M-H]- 350.9730, found 350.9736.
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4-Hydroxy-2-oxo-2H-chromen-3-yl benzenesulfonate (3af). Following the general
procedure, the reaction of 1a (49 mg, 0.3 mmol), 2f (136 mg, 0.36 mmol) and DCM
o
(10 mL) at 35 C for 1 h, after column chromatography on silica gel afforded 65 mg
(68%) of 3af as white solid. M.P.: 139-140 oC. 1H NMR (400 MHz, DMSO-d6) δ 8.03
– 7.97 (m, 2H), 7.96 – 7.91 (m, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.66 (t, J = 7.8 Hz, 3H),
7.39 (t, J = 8.1 Hz, 2H). A signal for OH-proton is not visible. 13C{1H} NMR (100
MHz, DMSO-d6) δ 158.1, 157.7, 151.1, 136.0, 134.6, 132.7, 129.3, 128.3, 124.3,
124.1, 116.7, 116.4. HRMS m/z (ESI-TOF): calculated for C15H9O6S [M-H]-
317.0120, found 317.0120.
4-Hydroxy-2-oxo-2H-chromen-3-yl 2,4-dinitrobenzenesulfonate (3ag). Following
the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2g (140 mg, 0.36 mmol)
o
and DCM (10 mL) at 35 C for 1 h, after column chromatography on silica gel
afforded 56 mg (46%) of 3ag as colourless oil. 1H NMR (400 MHz, DMSO-d6) δ 8.77
(d, J = 2.8 Hz, 1H), 8.34 (dd, J = 9.4, 2.8 Hz, 1H), 7.83 (dd, J = 7.7, 1.3 Hz, 1H), 7.53
– 7.45 (m, 1H), 7.22 (dd, J = 8.3, 6.7 Hz, 3H). A signal for OH-proton is not visible.
13C{1H} NMR (100 MHz, DMSO-d6) δ 159.1, 157.3, 152.3, 139.6, 137.7, 130.4,
129.0, 124.6, 122.5, 121.3, 117.5, 117.4, 115.9. HRMS m/z (ESI-TOF): calculated for
C15H7N2O10S [M-H]- 406.9821, found 406.9821.
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4-Hydroxy-2-oxo-2H-chromen-3-yl 4-(trifluoromethoxy)benzenesulfonate (3ah).
Following the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2h (167 mg,
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0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
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silica gel afforded 65 mg (54%) of 3ah as white solid. M.P.: 171-172 C. 1H NMR
(400 MHz, DMSO-d6) δ 8.19 – 8.10 (m, 2H), 7.95 (dd, J = 8.2, 1.5 Hz, 1H), 7.73 –
7.60 (m, 3H), 7.44 – 7.38 (m, 2H). A signal for OH-proton is not visible. 13C{1H}
NMR (100 MHz, DMSO-d6) δ 158.4, 157.7, 152.4, 151.1, 134.7, 132.8, 131.3, 124.4,
124.1, 121.2, 119.8(q, JC-F = 257 Hz), 116.7, 116.7, 116.5. HRMS m/z (ESI-TOF):
calculated for C16H9O7SF3K [M+K]+ 440.9659, found 440.9658.
4-Hydroxy-2-oxo-2H-chromen-3-yl 4-(trifluoromethyl)benzenesulfonate (3ai).
Following the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2h (161 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
silica gel afforded 83 mg (72%) of 3ai as white solid. M.P.: 186-187 C. 1H NMR
(400 MHz, DMSO-d6) δ 8.24 (d, J = 8.3 Hz, 2H), 8.04 (d, J = 8.4 Hz, 2H), 7.91 (dd, J
= 7.8, 1.3 Hz, 1H), 7.66 – 7.55 (m, 1H), 7.34 (t, J = 8.3 Hz, 2H). A signal for
OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 160.6, 158.2, 151.4,
140.8, 133.58(d, JC-F = 32 Hz), 132.1, 129.3, 126.3(q, JC-F = 4 Hz), 124.4, 123.8,
123.4(d, JC-F = 272 Hz), 118.7, 116.7, 116.3. HRMS m/z (ESI-TOF): calculated for
C16H9O6SF3Na [M+Na]+ 408.9970, found 408.9980.
4-Hydroxy-2-oxo-2H-chromen-3-yl 4-cyanobenzenesulfonate (3aj). Following the
general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2j (145 mg, 0.36 mmol) and
DCM (10 mL) at 35 oC for 1 h, after column chromatography on silica gel afforded 77
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mg (75%) of 3aj as white solid. M.P.: 167-168 C. 1H NMR (400 MHz, DMSO-d6) δ
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8.23 – 8.09 (m, 4H), 8.00 – 7.89 (m, 1H), 7.71 – 7.59 (m, 1H), 7.37 (t, J = 8.1 Hz, 2H).
A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 159.2,
157.9, 151.2, 140.3, 133.3, 132.6, 129.1, 124.2, 124.2, 117.5, 117.3, 116.8, 116.7,
116.4. HRMS m/z (ESI-TOF): calculated for C16H8NO6S [M-H]- 342.0072, found
342.0077.
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4-Hydroxy-2-oxo-2H-chromen-3-yl 4-nitrobenzenesulfonate (3ak). Following the
general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2k (152 mg, 0.36 mmol) and
DCM (10 mL) at 35 oC for 1 h, after column chromatography on silica gel afforded 78
o
mg (72%) of 3ak as white solid. M.P.: 132-133 C. 1H NMR (400 MHz, DMSO-d6) δ
8.44 (d, J = 8.9 Hz, 2H), 8.30 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 7.6 Hz, 1H), 7.60 (t, J =
7.2 Hz, 1H), 7.33 (t, J = 8.8 Hz, 2H). A signal for OH-proton is not visible. 13C{1H}
NMR (100 MHz, DMSO-d6) δ 161.1, 158.3, 151.5, 150.5, 142.4, 132.0, 130.0, 124.4,
124.3, 123.7, 119.0, 116.7, 116.2. HRMS m/z (ESI-TOF): calculated for C15H8NO8S
[M-H]- 361.9971, found 361.9978.
4-Hydroxy-2-oxo-2H-chromen-3-yl
4-(tert-butyl)benzenesulfonate
(3al).
Following the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2l (156 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
silica gel afforded 95 mg (85%) of 3al as white solid. M.P.: 75-77 C. 1H NMR (400
MHz, DMSO-d6) δ 7.88 (dd, J = 12.4, 5.1 Hz, 3H), 7.60 (dd, J = 10.9, 5.0 Hz, 3H),
7.39 – 7.20 (m, 2H), 1.25 (s, 9H). A signal for OH-proton is not visible. 13C{1H}
NMR (100 MHz, DMSO-d6) δ 157.9, 157.6, 157.6, 151.0, 133.0, 132.8, 128.3, 126.2,
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124.5, 124.0, 116.8, 116.5, 116.2, 35.1, 30.6. HRMS m/z (ESI-TOF): calculated for
C19H18O6SNa [M+Na]+ 397.0722, found 397.0732.
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4-Hydroxy-2-oxo-2H-chromen-3-yl 4-methoxybenzenesulfonate (3am). Following
the general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2m (147 mg, 0.36 mmol)
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and DCM (10 mL) at 35 C for 1 h, after column chromatography on silica gel
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afforded 94 mg (90%) of 3am as white solid. M.P.: 153-155 C. 1H NMR (400 MHz,
DMSO-d6) δ 7.98 – 7.81 (m, 3H), 7.72 – 7.61 (m, 1H), 7.41 (t, J = 7.5 Hz, 2H), 7.25 –
7.10 (m, 2H), 3.88 (s, 3H). A signal for OH-proton is not visible. 13C{1H} NMR (100
MHz, DMSO-d6) δ 163.9, 157.7, 157.6, 151.0, 132.7, 130.9, 126.9, 124.4, 124.0,
116.6, 116.4, 114.5, 55.9. HRMS m/z (ESI-TOF): calculated for C16H11O7S [M-H]-
347.0225, found 347.0229.
4-Hydroxy-2-oxo-2H-chromen-3-yl methanesulfonate (3an). Following the general
procedure, the reaction of 1a (49 mg, 0.3 mmol), 2n (114 mg, 0.36 mmol) and DCM
o
(10 mL) at 35 C for 1 h, after column chromatography on silica gel afforded 33 mg
(43%) of 3an as white solid. M.P.: 153-155 oC. 1H NMR (400 MHz, DMSO-d6) δ 7.98
(dd, J = 7.9, 1.2 Hz, 1H), 7.72 – 7.65 (m, 1H), 7.42 (dd, J = 12.0, 4.3 Hz, 2H), 3.48 (s,
3H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ
158.5, 158.1, 151.0, 132.6, 124.3, 124.1, 117.2, 117.0, 116.4, 39.7. HRMS m/z
(ESI-TOF): calculated for C10H7O6S [M-H]- 254.9963, found 254.9963.
4-Hydroxy-2-oxo-2H-chromen-3-yl naphthalene-2-sulfonate (3ao). Following the
general procedure, the reaction of 1a (49 mg, 0.3 mmol), 2o (154 mg, 0.36 mmol) and
DCM (10 mL) at 35 oC for 1 h, after column chromatography on silica gel afforded 65
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mg (59%) of 3ao as white solid. M.P.: 116-117 oC. 1H NMR (400 MHz, DMSO-d6) δ
8.68 (s, 1H), 8.24 – 8.14 (m, 3H), 8.12 – 8.04 (m, 1H), 7.82 (dd, J = 7.8, 1.6 Hz, 1H),
7.78 – 7.72 (m, 1H), 7.71 – 7.64 (m, 1H), 7.46 – 7.37 (m, 1H), 7.20 – 7.12 (m, 2H). A
signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 165.7,
159.6, 152.1, 135.7, 134.6, 131.4, 130.4, 129.4, 129.0, 128.9, 128.6, 127.8, 127.3,
124.8, 123.7, 123.4, 122.3, 116.4, 115.7. HRMS m/z (ESI-TOF): calculated for
C19H11O6S [M-H]- 367.0276, found 367.0276.
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4-Hydroxy-2-oxo-2H-chromen-3-yl((1R,2S,4R)-7,7-dimethyl-6-oxobicyclo[2.2.1]h
eptan-2-yl) methanesulfonate (3ap). Following the general procedure, the reaction
of 1a (49 mg, 0.3 mmol), 2p (163 mg, 0.36 mmol) and DCM (10 mL) at 35 oC for 1 h,
after column chromatography on silica gel afforded 65 mg (55%) of 3ap as white
o
solid. M.P.: 156-157 C. 1H NMR (400 MHz, DMSO-d6) δ 8.01 (dd, J = 8.1, 1.6 Hz,
1H), 7.71 – 7.54 (m, 1H), 7.45 – 7.28 (m, 2H), 3.89 (q, J = 15.1 Hz, 2H), 2.47 – 2.28
(m, 2H), 2.10 (t, J = 4.4 Hz, 1H), 1.98 (d, J = 18.4 Hz, 2H), 1.61 (ddd, J = 13.6, 9.4,
4.6 Hz, 1H), 1.51 – 1.38 (m, 1H), 1.08 (s, 3H), 0.87 (s, 3H). A signal for OH-proton is
not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 213.6, 160.5, 159.0, 151.3, 131.9,
124.4, 123.8, 118.9, 117.3, 116.2, 57.8, 54.9, 49.8, 47.7, 42.2, 41.9, 26.2, 24.9, 19.2.
HRMS m/z (ESI-TOF): calculated for C19H19O7S [M-H]- 391.0860, found 391.0852.
6-Fluoro-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ba).
Following the general procedure, the reaction of 1b (54 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
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silica gel afforded 60 mg (57%) of 3ba as white solid. M.P.: 89-90 C. H NMR (400
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MHz, DMSO-d6) δ 7.87 (d, J = 8.3 Hz, 2H), 7.45 (dd, J = 9.0, 3.1 Hz, 1H), 7.33 (d, J
= 8.0 Hz, 2H), 7.29 – 7.20 (m, 1H), 7.16 (dd, J = 8.9, 4.4 Hz, 1H), 2.34 (s, 3H). A
signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 163.7,
159.2, 157.7(d, JC-F = 237 Hz), 148.2, 143.8, 135.3, 129.2, 128.1, 117.8(d, JC-F = 6
Hz), 116.5, 109.8(d, JC-F = 24 Hz), 21.1. HRMS m/z (ESI-TOF): calculated for
C16H10O6SF [M-H]- 349.0182, found 349.0178.
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6-Chloro-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ca).
Following the general procedure, the reaction of 1c (59 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
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silica gel afforded 75 mg (68%) of 3ca as white solid. M.P.: 97-98 C. H NMR (400
MHz, DMSO-d6) δ 7.87 (d, J = 8.3 Hz, 2H), 7.68 (d, J = 2.7 Hz, 1H), 7.39 (dd, J =
8.7, 2.7 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.7 Hz, 1H), 2.34 (s, 3H). A
signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 164.2,
159.2, 150.7, 143.7, 135.5, 130.0, 129.1, 128.0, 126.7, 125.1, 123.9, 117.9, 116.3,
21.1. HRMS m/z (ESI-TOF): calculated for C16H10O6SCl [M-H]- 364.9887, found
364.9895.
6-Bromo-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3da).
Following the general procedure, the reaction of 1d (72 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
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silica gel afforded 80 mg (65%) of 3da as white solid. M.P.: 105-106 C. H NMR
(400 MHz, DMSO-d6) δ 7.94 (d, J = 2.5 Hz, 1H), 7.92 (d, J = 8.2 Hz, 2H), 7.65 (dd, J
= 8.7, 2.5 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.7 Hz, 1H), 2.42 (s, 3H). A
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signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 158.7,
150.8, 144.2, 134.8, 133.5, 129.3, 128.1, 126.8, 118.4, 116.5, 115.0, 21.1. HRMS m/z
(ESI-TOF): calculated for C16H10O6SBr [M-H]- 408.9381, found 408.9385.
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4-Hydroxy-6-methyl-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ea).
Following the general procedure, the reaction of 1e (53 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
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silica gel afforded 85 mg (82%) of 3ea as white solid. M.P.: 145-146 C. H NMR
(400 MHz, DMSO-d6) δ 7.91 (d, J = 8.3 Hz, 2H), 7.77 (s, 1H), 7.50 (d, J = 8.1 Hz,
3H), 7.33 (d, J = 8.4 Hz, 1H), 2.48 (s, 3H), 2.43 (s, 3H). A signal for OH-proton is not
visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 158.1, 157.8, 149.2, 145.3, 133.7,
133.4, 133.1, 129.7, 128.4, 123.7, 116.7, 116.5, 116.2, 21.2, 20.3. HRMS m/z
(ESI-TOF): calculated for C17H13O6S [M-H]- 345.0433, found 345.0428.
4-Hydroxy-6-methoxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3fa).
Following the general procedure, the reaction of 1f (58 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
1
silica gel afforded 54 mg (50%) of 3fa as white solid. M.P.: 144-145 C. H NMR
(400 MHz, DMSO-d6) δ 7.89 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.37 (d, J
= 3.0 Hz, 1H), 7.26 (d, J = 9.0 Hz, 1H), 7.17 (dd, J = 9.0, 3.0 Hz, 1H), 3.80 (s, 3H),
2.42 (s, 3H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz,
DMSO-d6) δ 158.4, 155.3, 145.6, 144.7, 134.0, 129.5, 128.3, 119.6, 117.5, 116.9,
106.2, 55.6, 21.1. HRMS m/z (ESI-TOF): calculated for C17H13O7S [M-H]- 361.0382,
found 361.0383.
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7-Fluoro-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ga).
Following the general procedure, the reaction of 1g (54 mg, 0.3 mmol), 2a (141 mg,
8
9
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
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11
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59
60
1
silica gel afforded 40 mg (38%) of 3ga as white solid. M.P.: 90-91 oC. H NMR (400
MHz, DMSO-d6) δ 7.96 (dd, J = 8.9, 6.2 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.45 (d, J
= 8.1 Hz, 2H), 7.37 (dd, J = 9.6, 2.4 Hz, 1H), 7.28 (td, J = 8.7, 2.5 Hz, 1H), 2.43 (s,
3H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ
164.1(d, JC-F = 249 Hz), 158.4, 157.7, 152.3(d, JC-F = 13 Hz), 145.2, 133.1, 129.7,
128.4, 126.4(d, JC-F = 11 Hz), 116.0, 114.14, 112.2(d, JC-F = 23 Hz), 104.0(d, JC-F = 26
Hz), 21.2. HRMS m/z (ESI-TOF): calculated for C16H10O6SF [M-H]- 349.0182, found
349.0175.
7-Chloro-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ha).
Following the general procedure, the reaction of 1h (59 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
1
silica gel afforded 58 mg (53%) of 3ha as white solid. M.P.: 85-86 C. H NMR (400
MHz, DMSO-d6) δ 7.88 (t, J = 9.3 Hz, 3H), 7.52 (s, 1H), 7.42 (t, J = 9.1 Hz, 3H),
2.41 (s, 3H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz,
DMSO-d6) δ 158.9, 157.6, 151.6, 145.1, 136.5, 133.4, 129.6, 128.3, 125.8, 124.3,
117.0, 116.5, 116.4, 21.1. HRMS m/z (ESI-TOF): calculated for C16H10O6SCl [M-H]-
364.9887, found 364.9887.
7-Bromo-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ia).
Following the general procedure, the reaction of 1i (72 mg, 0.3 mmol), 2a (141 mg,
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0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
6
7
8
9
o
1
silica gel afforded 75 mg (61%) of 3ia as white solid. M.P.: 95-96 C. H NMR (400
MHz, DMSO-d6) δ 7.94 (d, J = 2.5 Hz, 1H), 7.92 (d, J = 8.2 Hz, 2H), 7.65 (dd, J =
8.7, 2.5 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.7 Hz, 1H), 2.42 (s, 3H). A
signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 159.6,
157.8, 151.6, 145.0, 133.5, 129.6, 128.3, 126.9, 126.0, 124.8, 119.1, 117.8, 116.6,
21.1. HRMS m/z (ESI-TOF): calculated for C16H10O6SBr [M-H]- 408.9381, found
408.9384.
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4-Hydroxy-7-methoxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ja).
Following the general procedure, the reaction of 1j (58 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
silica gel afforded 76 mg (70%) of 3ja as white solid. M.P.: 134-135 C. 1H NMR
o
(400 MHz, DMSO-d6) δ 7.83 (d, J = 8.3 Hz, 2H), 7.72 (d, J = 8.8 Hz, 1H), 7.35 (d, J
= 8.0 Hz, 2H), 6.83 (dd, J = 8.8, 2.4 Hz, 1H), 6.78 (d, J = 2.4 Hz, 1H), 3.76 (s, 3H),
2.35 (s, 3H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz,
DMSO-d6) δ 162.2, 158.7, 153.1, 144.5, 134.2, 129.4, 128.2, 125.5, 115.2, 111.4,
100.3, 55.8, 21.1. HRMS m/z (ESI-TOF): calculated for C17H13O7S [M-H]- 361.0382,
found 361.0376.
7-(Dimethylamino)-4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate
(3ka). Following the general procedure, the reaction of 1k (62 mg, 0.3 mmol), 2a
o
(141 mg, 0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column
chromatography on silica gel afforded 72 mg (64%) of 3ka as grey solid. M.P.:
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o
168-169 C. 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J = 8.3 Hz, 2H), 7.70 (d, J =
9.0 Hz, 1H), 7.45 (d, J = 8.1 Hz, 2H), 6.77 (dd, J = 9.1, 2.4 Hz, 1H), 6.52 (d, J = 2.3
Hz, 1H), 3.02 (s, 6H), 2.43 (s, 3H). A signal for OH-proton is not visible. 13C{1H}
NMR (100 MHz, DMSO-d6) δ 158.4, 158.1, 153.3, 153.2, 145.2, 133.1, 129.7, 128.4,
124.6, 113.6, 109.3, 103.4, 97.2, 38.9, 21.2. HRMS m/z (ESI-TOF): calculated for
C18H16NO6S [M-H]- 374.0698, found 374.0698.
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60
4-Hydroxy-8-methyl-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3la).
Following the general procedure, the reaction of 1l (53 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
1
silica gel afforded 80 mg (77%) of 3la as white solid. M.P.: 146-147 C. H NMR
(400 MHz, DMSO-d6) δ 7.88 (d, J = 8.3 Hz, 2H), 7.77 (d, J = 7.0 Hz, 1H), 7.52 (d, J
= 7.3 Hz, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.28 (t, J = 7.7 Hz, 1H), 2.44 (s, 3H), 2.34
(s,3H). A signal for OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ
158.5, 157.7, 149.4, 145.2, 133.6, 133.2, 129.7, 128.4, 125.3, 123.9, 121.8, 116.7,
116.6, 21.2, 15.2. HRMS m/z (ESI-TOF): calculated for C17H13O6S [M-H]- 345.0433,
found 345.0440.
4-Hydroxy-5-methyl-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (3ma).
Following the general procedure, the reaction of 1m (53 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
silica gel afforded 83 mg (80%) of 3ma as white solid. M.P.: 96-97 oC. 1H NMR (400
MHz, DMSO-d6) δ 7.86 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.0
Hz, 2H), 7.26 – 7.18 (m, 2H), 2.43 (s, 3H), 2.41 (s, 3H). A signal for OH-proton is not
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visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 158.3, 157.8, 151.1, 145.3, 143.5,
133.0, 129.7, 128.4, 125.4, 123.8, 116.4, 116.1, 114.1, 21.2, 21.0. HRMS m/z
(ESI-TOF): calculated for C17H13O6S [M-H]- 345.0433, found 345.0433.
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1-Hydroxy-3-oxo-3H-benzo[f]chromen-2-yl 4-methylbenzenesulfonate (3na).
Following the general procedure, the reaction of 1n (64 mg, 0.3 mmol), 2a (141 mg,
o
0.36 mmol) and DCM (10 mL) at 35 C for 1 h, after column chromatography on
o
1
silica gel afforded 89 mg (78%) of 3na as white solid. M.P.: 208-209 C. H NMR
(400 MHz, DMSO-d6) δ 9.42 (d, J = 8.7 Hz, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.09 (d, J
= 7.3 Hz, 1H), 7.95 (d, J = 8.3 Hz, 2H), 7.78 – 7.72 (m, 1H), 7.68 – 7.62 (m, 1H),
7.55 (d, J = 9.0 Hz, 1H), 7.50 (d, J = 8.1 Hz, 2H), 2.48 (s, 3H). A signal for
OH-proton is not visible. 13C{1H} NMR (100 MHz, DMSO-d6) δ 157.1, 152.2, 145.2,
134.0, 132.9, 130.3, 129.6, 129.4, 128.9, 128.6, 128.3, 125.7, 117.6, 117.0, 21.2.
HRMS m/z (ESI-TOF): calculated for C20H13O6S [M-H]- 381.0433, found 381.0442.
4-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl 4-methylbenzenesulfonate
(3oa). Following the general procedure, the reaction of 1o (53 mg, 0.3 mmol), 2a (141
mg, 0.36 mmol) and DCM (10 mL) at 35 oC for 1 h, after column chromatography on
o
1
silica gel afforded 75 mg (72%) of 3oa as white solid. M.P.: 111-112 C. H NMR
(400 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.02 (dd, J = 8.0, 1.3 Hz, 1H), 7.93 (d, J = 8.3
Hz, 2H), 7.72 – 7.63 (m, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.37
– 7.29 (m, 1H), 3.55 (s, 3H), 2.44 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ
157.9, 152.9, 144.9, 137.7, 133.8, 131.5, 129.5, 128.3, 123.7, 122.3, 122.0, 115.4,
114.8, 29.2, 21.1. HRMS m/z (ESI-TOF): calculated for C17H14NO5S [M-H]-
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344.0593, found 344.0586.
4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl
4-methylbenzenesulfonate
(3pa).
8
9
Following the general procedure, the reaction of 1p (38 mg, 0.3 mmol), 2a (141 mg,
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0.36 mmol) and DCM (3 mL) at 35 oC for 1 h, after column chromatography on silica
o
gel afforded 79 mg (95%) of 3pa as white solid. M.P.: 117-118 C. 1H NMR (400
MHz, DMSO-d6) δ 12.37 (s, 1H), 7.84 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H),
6.04 (s, 1H), 2.43 (s, 3H), 2.18 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ 161.9,
161.2, 159.4, 145.0, 133.6, 129.7, 128.1, 115.2, 99.8, 21.1, 19.2. HRMS m/z
(ESI-TOF): calculated for C13H12O6SNa [M+Na]+ 319.0252, found 319.0243.
2-Oxo-4-(((trifluoromethyl)sulfonyl)oxy)-2H-chromen-3-yl 4-methylbenzenesulfo
-nate
(4).
To
a
250
ml
round-bottomed
flask
was
added
4-hydroxy-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate 3aa (5 mmol, 1.66 g)
and Tf2O (10 mmol, 2.82 g). DCM (20 ml) was added and Et3N (0.5 mL) was slowly
dropped to the solution. Then the mixture was stirred at room temperature for 3 hours.
After TLC, the solvent was evaporated under vacuum. The crude products were
purified using flash column chromatography on silica gel to afford 2.13 g (92%) of
the desired product 4 as white solid. M.P.: 156-157 oC. 1H NMR (400 MHz, CDCl3) δ
7.98 (d, J = 8.4 Hz, 2H), 7.78 – 7.66 (m, 2H), 7.55 – 7.37 (m, 4H), 2.50 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 151.1, 145.5, 143.0, 141.4, 128.6, 127.2, 124.7,
123.7, 119.4(q, J C-F = 220 Hz), 112.1, 109.5, 16.6. HRMS m/z (ESI-TOF): calculated
for C17H12O8S2F3 [M+H]+ 464.9926, found 464.9927.
2-Oxo-4-((2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl)oxy)-2H-
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chromen-3-yl 4-methylbenzenesulfonate (5). To a solution of 4 (0.2 mmol, 97 mg )
in DMF (2 ml), Vitamin E (0.24 mmol, 103 mg) and K2CO3 (0.4 mmol, 55 mg) was
added. Then the mixture was stirred at 100 oC under oil bath for 12 hours. After TLC,
water (20 mL) was added, and the mixture was firstly extracted with DCM and then
dried over anhydrous Na2SO4 and concentrated in vacuo. The crude compound was
purified by column chromatography on silica gel to afford 63 mg (42%) of desired
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product 5 as colourless oil. H NMR (400 MHz, CDCl3) δ 7.97 (t, J = 7.0 Hz, 1H),
7.67 (d, J = 8.3 Hz, 2H), 7.59 (t, J = 7.7 Hz, 1H), 7.34 (t, J = 6.9 Hz, 2H), 7.29 – 7.22
(m, 2H), 2.63 (s, 2H), 2.42 (s, 3H), 2.14 (s, 3H), 2.08 (s, 6H), 1.92 – 1.78 (m, 2H),
1.60 (s, 2H), 1.57 – 1.47 (m, 2H), 1.40 (d, J = 20.1 Hz, 4H), 1.34 – 1.19 (m, 10H),
1.13 (dd, J = 11.7, 7.1 Hz, 3H), 1.06 (dd, J = 7.6, 4.7 Hz, 3H), 0.90 – 0.80 (m, 12H).
13C{1H} NMR (100 MHz, CDCl3) δ 158.7, 154.7, 150.9, 149.5, 144.8, 134.5, 132.4,
129.3, 128.4 126.0, 124.7, 124.5, 124.3, 123.3, 118.0, 116.8, 116.4, 75.2, 39.4, 37.4,
32.8, 28.0, 27.0, 24.9, 24.5, 22. 8, 22.7, 20. 8, 13.3, 12.0. HRMS m/z (ESI-TOF):
calculated for C45H60NaO7S [M+Na]+ 767.3957, found 767.3956.
4-(Furan-3-yl)-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (6). To
a
solution of 4 (0.2 mmol, 97 mg ) in toluene (2 ml), furan (1 mmol, 68 mg) was added
o
under argon atmosphere at 0 C. Then LiHDMs (0.2 mmol) was also slowly added at
the same temperature and the mixture was stirred for additional 12 h. After TLC,
water (20 mL) was added, and the mixture was firstly extracted with DCM and then
dried over anhydrous Na2SO4 and concentrated in vacuo. The crude compound was
purified by column chromatography on silica gel to afford 40 mg (52%) of desired
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product 6 as white solid. M.P.: 191-192 C. H NMR (400 MHz, DMSO-d6) δ 7.99 –
6
7
7.88 (m, 3H), 7.62 (s, 1H), 7.56 (d, J = 8.1 Hz, 2H), 7.29 – 7.14 (m, 2H), 6.94 (td, J =
8
9
13
7.6, 1.0 Hz, 1H), 6.86 – 6.81 (m, 1H), 6.60 (d, J = 2.6 Hz, 1H), 2.47 (s, 3H). C{1H}
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NMR (100 MHz, DMSO-d6) δ 162.8, 154.1, 151.3, 146.3, 138.5, 130.8, 130.4, 130.3,
128.5, 128.4, 122.6, 121.9, 120.2, 118.5, 102.4, 79.9, 76.7, 21.2. HRMS m/z
(EI-TOF): calculated for C20H14O6S [M]+ 382.0511, found 382.0513.
2-Oxo-4-(p-tolylthio)-2H-chromen-3-yl 4-methylbenzenesulfonate (7). To a
solution of 4 (0.2 mmol, 97 mg ) in toluene (2 ml), 4-methylbenzenethiol (0.24 mmol,
o
30 mg) was added under argon atmosphere at 0 C. Then LiHDMs (0.2 mmol) was
o
also slowly added at the same temperature and the mixture was stirred at 110 C under
oil bath for additional 12 h. After TLC, water (20 mL) was added, and the mixture
was firstly extracted with DCM and then dried over anhydrous Na2SO4 and
concentrated in vaccum. The crude compound was purified by column
chromatography on silica gel to afford 55 mg (63%) of desired product 7 as white
solid. M.P.: 142-143 oC. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 2H), 7.76
(dd, J = 8.1, 1.2 Hz, 1H), 7.47 – 7.37 (m, 1H), 7.31 – 7.22 (m, 3H), 7.13 (td, J = 8.3,
1.5 Hz, 3H), 6.99 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H), 2.23 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 155.6, 151.1, 145.7, 143.7, 138.2, 136.0, 133.7, 131.9, 130.9, 130.3,
129.7, 128.8, 128.7, 128.0, 124.8, 119.0, 117.0, 21.8, 21.1. HRMS m/z (ESI-TOF):
calculated for C23H19O5S2 [M+H]+ 439.0674, found 439.0675.
4-(Diphenylphosphanyl)-2-oxo-2H-chromen-3-yl 4-methylbenzenesulfonate (8).
To a solution of 4 (0.2 mmol, 97 mg ) in toluene (2 ml), diphenylphosphane (0.24
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mmol, 45 mg) was added under argon atmosphere at 0 C. Then LiHDMs (0.2 mmol)
6
7
o
was also slowly added at the same temperature and the mixture was stirred at 110 C
8
9
under oil bath for additional 12 h. After TLC, water (20 mL) was added, and the
mixture was firstly extracted with DCM and then dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude compound was purified by column chromatography
10
11
12
13
14
15
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19
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21
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23
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on silica gel to afford 52 mg (52%) of desired product 8 as colourless oil. H NMR
(400 MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 2H), 7.76 (dd, J = 8.1, 1.2 Hz, 1H), 7.47 –
7.37 (m, 1H), 7.31 – 7.22 (m, 3H), 7.13 (td, J = 8.3, 1.5 Hz, 3H), 6.99 (d, J = 8.0 Hz,
2H), 2.39 (s, 3H), 2.23 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 155.6, 151.1,
145.7, 143.7, 138.2, 136.0, 133.7, 131.9, 130.9, 130.3, 129.7, 128.8, 128.7, 128.0,
124.8, 119.0, 117.0, 21.8, 21.1. HRMS m/z (ESI-TOF): calculated for C28H22O5PS
[M+H]+ 501.0926, found 501.0927.
2-Oxo-3-(phenyliodonio)-2H-chromen-4-olate (11). To a 50 ml round-bottomed
flask was added 4-hydroxy-2H-chromen-2-one 1a (1 mmol) and DCM (20 ml). Then
the temperature was cooled to 0 oC and [hydroxy(sulfonyloxy)iodo]arenes 2 (1 mmol)
was added slowly. After stirring for 15 minutes, the solvent was evaporated under
vacuum. The crude products were purified using flash column chromatography on
silica gel to afford 302 mg (83%) of the desired product 11 as pale yellow solid. M.P.:
o
1
136-137 C. H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 7.7 Hz, 1H), 7.86 (d, J =
8.3 Hz, 2H), 7.61 – 7.50 (m, 2H), 7.43 (t, J = 7.6 Hz, 2H), 7.32 – 7.21 (m, 2H).
13C{1H} NMR (100 MHz, DMSO-d6) δ 172.5, 161.0, 153.9, 133.1, 132.8, 131.1,
130.7, 125.6, 123.4, 119.8, 116.3, 115.0, 82.0. HRMS m/z (EI-TOF): calculated for
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