Iridium-catalyzed direct arene C-H bond amidation with sulfonyl- and aryl azides

Article abstract of DOI:10.1021/jo4019683

Iridium-catalyzed direct ortho C-H amidation of arenes has been shown to work well with sulfonyl- and aryl azides as the nitrogen source. The reaction proceeds efficiently with a broad range of substrates bearing conventional directing groups with excellent functional group compatibility under mild conditions. In addition, substrates forming not only 5- but also 6-membered iridacycle intermediates undergo the C-H amidation with high selectivity.

Full text of DOI:10.1021/jo4019683

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Note
Iridium-Catalyzed Direct Arene C-H Bond
Amidation with Sulfonyl- and Aryl Azides
Donggun Lee, Youngchan Kim, and Sukbok Chang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 01 Oct 2013
Downloaded from http://pubs.acs.org on October 1, 2013
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Iridium-Catalyzed Direct Arene C−H Bond Amidation with Sulfonyl- and Aryl Azides
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Donggun Lee,2,1 Youngchan Kim,2,1 and Sukbok Chang*,1,2
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1 Center for Catalytic Hydrocarbon Functionalizations, Institute of Basic Science (IBS), Daejon 307-701, Republic of Korea
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2 Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST); Daejon 307-701, Republic of
Korea
sbchang@kaist.ac.kr
Abstract
Iridiumꢀcatalyzed direct ortho C−H amidation of arenes has been shown to work well with sulfonylꢀ
and aryl azides as the nitrogen source. The reaction proceeds efficiently with a broad range of
substrates bearing conventional directing groups with excellent functional group compatibility under
mild conditions. In addition, substrates forming not only 5ꢀ but also 6ꢀmembered iridacycle
intermediates undergo the C−H amidation with high selectivity.
Transition metalꢀcatalyzed C−N bond formation has attracted a great attention because of its high synthetic
values in diverse research areas.1 In particular, the Cuꢀ and Pdꢀcatalyzed Nꢀarylation of aryl(pseudo)halides has
been extensively explored.2ꢀ3 More recently, a direct C−H amination strategy has been actively investigated using
arenes instead of aryl halides to react with either amines or preꢀactivated amino precursors.4 In these procedures,
oxidative conditions are applied when amines are allowed to react.5 On the other hand, the amination takes place
in the absence of external oxidants when preꢀactivated amino precursors such as halogenated amines are
employed, but generating halide salts as the byproducts.6
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In our continuing efforts to develop efficient and selective C−N bondꢀforming reactions,7 we recently disclosed
Rhꢀ and Ruꢀcatalyzed direct C−H amination protocols using organic azides as the amino source (Scheme 1a).8ꢀ9
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Scheme 1.
The reactions are characterized to have wide substrate scope, mild conditions, and high functional group
tolerance. Significantly, the amination proceeds in the absence of external oxidants to release molecular nitrogen
as the single byproduct. It was demonstrated that a wide range of azides could be applicable upon the choice of
catalytic systems.10ꢀ11
More recently, acyl azides were also efficiently utilized in the direct amidation of arenes and alkenes under Irꢀ
catalyzed conditions.12 Described herein is a new aspect of this chemistry: not only the scope of amino sources
are expanded now to include sulfonylꢀ and aryl azides, but also the amidation of a new type of substrates forming
a 6ꢀmembered iridacycle intermediate can be successfully amidated (Scheme 1b).
We initially tried to optimize the amidation conditions in a reaction of Nꢀtertꢀbutylbenzamide (1a) with pꢀ
toluenesulfonyl azide (2a) (Table 1). High yield of the desired product 3a was obtained at 80 °C when
[IrCp*Cl2]2 (2 mol %) was used in the presence of AgNTf2 additive (entry 2), and the reaction did not proceed in
the absence of a silver additive (entry 1). While a similar yield was also obtained at 50 °C (entry 3), different
silver species and solvents other than 1,2ꢀdichloroethane were less effective (entries 4−8). It is noteworthy that
the amidation took place even at room temperature albeit with slightly lower yield under the present catalyst
system (entry 9). Interestingly, previously reported other catalytic systems8ꢀ9 including [RhCp*Cl2]2 and [Ru(pꢀ
cymene)Cl2]2 displayed much lower activity when compared to the current iridium system at 50 °C (entries
10−11).
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Table 1. Optimization of the Ir-Catalyzed Amidationa
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temp yield
entry
catalyst
additive
solvent
(°C) (%)b
1
2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[IrCp*Cl2]2
[RhCp*Cl2]2
ꢀ
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
Toluene
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80
50
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25
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N.R.
90
87
84
57
75
14
32
78
3
AgNTf2
AgNTf2
AgSbF6
AgPF6
3
4
5
6
AgBF4
AgNTf2
AgNTf2
AgNTf2
AgSbF6
7
8
tꢀAmylOH
9
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
10
11 [Ru(pꢀcymene)Cl2]2 AgNTf2
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a
Reaction conditions: 1a (0.2 mmol), 2a (1.1 equiv), catalyst (2 mol %), additive (8 mol %) in solvent (0.5 mL) at the indicated
temperature for 12 h. b Yield was determined by 1H NMR spectroscopy by using anisol as an internal standard.
With the optimized conditions in hand, we then investigated the scope of benzamide substrates in reaction with
pꢀtoluenesulfonyl azide (Scheme 2). Electronic variation of substituents did not much influence the reaction
efficiency (3a−3e). The amidation conditions were compatible with various functional groups such as fluoro,
chloro, bromo, ester, free hydroxy and its acetate (3f−3k). In addition, the amidation was highly regioselective as
proved in the reaction of metaꢀsubstituted benzamide and 2ꢀnaphthamide (3l and 3m, respectively). Variation of
the Nꢀalkyl moiety of secondary benzamides was observed to be highly flexible (3n−3q). Moreover, the
amidation of benzamide was easily scaledꢀup without difficulty even using 1 mol % of the Ir catalyst (3a).
The scope of organic azides was subsequently examined in the amidation of N-tertꢀbutylbenzamide (Scheme
3). Arenesulfonyl azides substituted with methoxy, chloro, trifluoromethyl, and acetamido groups were reacted
without difficulty (4a−4d). Aliphatic variants also worked well (4e−4f). In addition, aryl azides readily
participated in the direct amination to provide N,Nꢀdiarylamines (4g−4i).
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Scheme 2. Scope of Benzamidesa
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a Reaction conditions : 1 (0.2 mmol), 2a (1.1 equiv), [IrCp*Cl2]2 (2 mol %), AgNTf2 (8 mol %) in 1,2ꢀdichloroethane (0.5 mL) at 50 °C
for 12 h. b 1 (1.0 g, 5.6 mmol), 2a (1.0 equiv), [IrCp*Cl2]2 (1 mol %), AgNTf2 (4 mol %) in 1,2ꢀdichloroethane (7.5 mL) at 50 °C for 12 h.
Scheme 3. Scope of Sulfonyl- and Aryl Azidesa
a
Reaction conditions: 1 (0.2 mmol), 2 (1.1 equiv), [IrCp*Cl2]2 (2 mol %), AgNTf2 (8 mol %) in 1,2ꢀdichloroethane (0.5 mL) at 50 °C
for 12 h. b Substrates (1.8 equiv, 0.36mmol) were used.
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After successful exploration of the scope of benzamides in the direct amidation, we turned our attention to
substrates bearing readily removable directing groups (Scheme 4).13
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Scheme 4. Scope of Aryl Carbamatesa
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a
Reaction conditions: 5 (1.8 equiv, 0.36 mmol), 2a (0.2 mmol), [IrCp*Cl2]2 (4 mol %), AgNTf2 (16 mol %), Cu(OAc)2 (10 mol %) in
1,2ꢀdichloroethane (0.5 mL) at 50 °C for 12 h.
We decided to examine aryl carbamates first since they are also easily prepared from the corresponding phenols.14
Those substrates were found to undergo the amidation with high efficiency under slightly modified conditions,
but requiring acetate additive in this case. Among acetate additives screened, Cu(OAc)2 showed the highest
reaction efficiency while NaOAc provided slightly lower yields. Although the exact role of acetate additive is not
clear at this stage, it is assumed that an acetate facilitates the ligand exchange in the cationic iridium species to
increase the catalytic activity in the C−
H activation process.15
The amidation took place smoothly irrespective of the electronic nature of substrates (6a−6c). It was observed
that substituents positioned at the ortho or meta relative to the carbamate group slightly decreased the reactivity
(6d−6e). Variation of Nꢀsubstituents of aryl carbamates did not result in any deteriorating effects (6f−6h). In a
sharp contrast, our previous Rhꢀ and Ruꢀcatalytic systems were ineffective for this type of substrates (<5% yields).
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The facile reaction of aryl carbamates observed above is significant in that the Irꢀcatalyzed direct C−H
amidation approach can now be applicable to substrates forming not only 5ꢀ but also 6ꢀmembered iridacycle
intermediates.
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Additional substrates bearing various coordinating groups were next investigated (Scheme 5).
Scheme 5. Scope of Various Chelating Groupsa
a
Reaction conditions: 7 (0.2 mmol), 2a (1.1 equiv), [IrCp*Cl2]2 (4 mol %), AgNTf2 (16 mol %) in 1,2ꢀdichloroethane (0.5 mL) at 80
°C for 12 h. b For 24 h. c Substrates (1.8 equiv, 0.36 mmol) were used. d At 50 °C.
We were pleased to see that representative chelates such as ketoxime, substituted hydrazone, 2ꢀpyridine, 2ꢀ
pyrazol, and 2ꢀazoline all facilitated the ortho C−H amidation albeit at slightly higher temperature (8a−8e).
Moreover, 2ꢀbenzylpyridine, anilides, and Nꢀphenylꢀpyrrolidone underwent the amidation in high yields
presumabably through the corresponding 6ꢀmembered iridacycles (8f−8i).
Direct C−H amidation of heterocycles was briefly examined since the products are widely utilized in medicinal
and coordination chemistry (Scheme 6).16 Reaction of 2ꢀphenylbenzoxazole was smooth to afford the
corresponding amidated product (10a) that is often used as a precursor of biosensors or biologically active
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ligands. 1ꢀArylisoquinoline derivatives were also amidated in the presence of acetate additives. As mentioned
above, we assume that an acetate additive facilitates C−H bond activation process for substrates especially
showing low reactivity.15 In this case, unlike aryl carbamates, NaOAc displayed higher additive effects. 1ꢀ(2ꢀ
Amidonaphthyl)isoquinoline (10b) was obtained in high yield, which was utilized in catalysis or for the
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stereoselective synthesis by forming chiral β
ꢀdiketimineꢀsupported metal complexes.17 Again, an excellent level
of functional group tolerance was observed in the amidation of 1ꢀarylisoquinoline derivatives (10d−10f).18
Scheme 6. Scope of Benzoxazole and Isoquinolinesa
a
Reaction conditions: 9 (0.2 mmol), 2a (1.1 equiv), [IrCp*Cl2]2 (4 mol %), AgNTf2 (16 mol %), NaOAc(20 mol %) in 1,2ꢀ
dichloroethane (0.5 mL) at 80 °C for 12 h. b Substrate (1.8 equiv, 0.36 mmol) was used in the absence of NaOAc.
Described herein is the Irꢀcatalyzed direct C(sp2)−H amidation of arenes with sulfonylꢀ and aryl azides as the
amino source. The procedure is convenient to carry out under mild conditions, and a wide range of substrates
forming not only 5ꢀ but also 6ꢀmembered iridacycle intermediates are efficiently amidated with high functional
group tolerance. The amidated products have versatile utilities in such areas as organic synthesis and coordination
or medicinal chemistry.
Experimental Section
General Methods. Unless otherwise stated, all commercial reagents and solvents were used without additional
purification. Thin layer chromatography (TLC) was performed on 0.25 mm silica gel 60 plates. Visualization on
TLC was achieved by the use of UV light (254 nm). Column chromatography was undertaken on silica gel using
a proper eluent system. 1H NMR was recorded 400 MHz spectrometer, referenced to the appropriate solvent peak
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or 0.0 ppm for tetramethylsilane. The following abbreviations were used to describe peak splitting patterns when
appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublet, td = triplet of
doublet, ddd = doublet of doublet of doublet, m = multiplet. Coupling constants, J, were reported in hertz unit
(Hz). 13C NMR was recorded on 100 MHz spectrometer, referenced to the center of a triplet at 77.0 ppm of
chloroformꢀd. High resolution mass spectra (HRMS) were acquired with TimeꢀofꢀflightꢀQuadrupole (TOFꢀQ) via
electron spray ionization (ESI) or with a magnetic sector−electric sector via electron ionization (EI). Infrared (IR)
spectra were recorded neat in 0.5 mm path length using a NaCl cell. Frequencies are given in reciprocal
centimeters (cm−1) and only selected absorbance is reported. All solvents were freshly distilled before used, and
other reagents or catalysts were directly used from purchased without further purification unless otherwise
specified.
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Preparation of substrates. Benzamides 1,8b organic azides 2,9 aryl carbamates 5,14b ketoximes (7a),19
tosylhydrazone derivatives (7b),20 anilides (7g−7h),21 2ꢀphenylbenzoxazole (9a),22 and 1ꢀarylisoquinoline
derivatives (9b−9f)23 were prepared according to the previously reported procedures.
General procedure for the amidation of benzamides with organic azides. To a screw capped vial
with a spinvane triangularꢀshaped Teflon stir bar were added benzamide (1, 0.2 mmol), sulfonylꢀ or aryl azide (2,
0.22 mmol), [IrCp*Cl2]2 (3.2 mg, 0.004 mmol, 2 mol %), AgNTf2 (6.2 mg, 0.016 mmol, 8 mol %) and 1,2ꢀ
dichloroethane (0.5 mL) under atmospheric conditions. The reaction mixture was stirred in a preꢀheated oil bath
ο
at 50 C for 12 h, filtered through a pad of celite and then washed with EtOAc (10 mL × 3). Organic solvents
were removed under reduced pressure and the residue was purified by chromatography on silica gel (nꢀ
hexane/EtOAc) to give the desired product 3 or 4.
N-(tert-Butyl)-2-(4-methylphenylsulfonamido)-4-nitrobenzamide (3e). White solid (63.1 mg, 80%);
m.p. 201−203 °C; 1H NMR (400 MHz, CDCl3) δ 10.90 (s, 1H), 8.42 (d, J = 2.2 Hz, 1H), 7.74 (dd, J = 8.6, 2.2 Hz,
1H), 7.70 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 8.6 Hz, 1H), 7.26 − 7.20 (m, 2H), 6.20 (s, 1H), 2.37 (s, 3H), 1.44 (s,
13
9H); C NMR (100 MHz, CDCl3) δ 166.4, 149.5, 144.4, 139.8, 136.0, 129.9, 128.2, 127.2, 126.8, 117.4, 114.8,
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53.0, 28.5, 21.5; IR (NaCl) 3415, 2087, 1644, 1399, 1352, 1254, 1161, 1092, 966, 769, 618 cmꢀ1; HRMS (ESI)
m/z calcd. for C18H21N3O5S [M
Na]+: 414.1100, found: 414.1087. Rf (nꢀhexane/EtOAc, 3/1): 0.34
7
8
+
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N-(tert-Butyl)-2-fluoro-6-(4-methylphenylsulfonamido)benzamide (3f). White solid (58.5 mg, 80%);
m.p. 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 11.33 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.49 (m, J = 8.5, 0.9 Hz,
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1H), 7.32 − 7.24 (m, 1H), 7.21 (m, J = 8.0, 0.7 Hz, 2H), 6.76 (ddd, J = 12.0, 8.3, 1.1 Hz, 1H), 6.41 (d, J = 13.8
Hz, 1H), 2.37 (s, 3H), 1.40 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.0, 164.0, 161.6, 159.2, 143.6, 141.0,
141.0, 136.7, 132.4, 132.3, 129.6, 127.2, 116.9, 116.9, 110.9, 110.8, 110.7, 52.4, 28.7, 21.5; IR (NaCl) 3464,
3381, 2972, 2086, 1644, 1614, 1580, 1537, 1462, 1368, 1311, 1232, 1185, 1163, 1092, 1024, 805, 706, 661 cmꢀ1;
HRMS (EI) m/z calcd. for C18H21FN2O3S [M]+: 364.1257, found: 364.1255; Rf (nꢀhexane/EtOAc, 3/1): 0.35.
4-Bromo-N-(tert-butyl)-2-(4-methylphenylsulfonamido)benzamide (3h). Light yellow solid (71.1
mg, 84%); m.p. 201−203 °C; 1H NMR (400 MHz, CDCl3) δ 10.93 (s, 1H), 7.84 (d, J = 1.9 Hz, 1H), 7.68 (d, J =
8.4 Hz, 2H), 7.24−7.18 (m, 2H), 7.19−7.06 (m, 2H), 5.85 (s, 1H), 2.37 (s, 3H), 1.39 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 167.4, 143.8, 140.0, 136.5, 129.7, 127.8, 127.1, 126.4, 126.3, 123.9, 121.0, 52.4, 28.6, 21.5; IR (NaCl)
3392, 2961, 2925, 2870, 1639, 1588, 1566, 1529, 1479, 1456, 1375, 1335, 1251, 1185, 1089, 941, 915, 774, 686
cm−1; HRMS (EI) m/z calcd. for C18H21BrN2O3S [M]+: 424.0456, found: 424.0455; Rf (nꢀhexane/EtOAc, 3/1):
0.32.
2-(4-Acetamidophenylsulfonamido)-N-(tert-butyl)benzamide (4d). White solid (46.8 mg, 60%); m.p.
167−169 °C; 1H NMR (400 MHz, , CDCl3) δ 10.85 (s, 1H), 8.04 (s, 1H), 7.64−7.57 (m, 3H), 7.51 (d, J = 8.8 Hz,
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2H), 7.38−7.28 (m, 2H), 7.02 (td, J = 7.4, 1.1 Hz, 1H), 6.00 (s, 1H), 2.14 (s, 3H), 1.39 (s, 9H); C NMR (100
MHz, CDCl3) δ 169.1, 168.1, 142.2, 138.3, 133.9, 132.2, 128.2, 126.9, 123.8, 123.0, 121.5, 119.4, 52.3, 28.6,
24.5; IR (NaCl) 3355, 3191, 3114, 3062, 2971, 2929, 1686, 1637, 1593, 1532, 1493, 1402, 1368, 1330, 1265,
1186, 1159, 1093, 937, 612, 564, cm−1; HRMS (EI) m/z calcd. for C19H23N3O4S [M]+: 389.1409, found: 389.1406;
Rf (nꢀhexane/EtOAc, 1/1): 0.28.
2-[{3,5-Bis(trifluoromethyl)phenyl}amino]-N-(tert-butyl)-4-methoxybenzamide (4h). White solid
(57.8 mg, 65%); m.p. 123−126 °C; 1H NMR (400 MHz, CDCl3) δ 10.14 (s, 1H), 7.62 (s, 2H), 7.41 (d, J = 0.7 Hz,
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1H), 7.35 (d, J = 8.7 Hz, 1H), 6.86 (d, J = 2.5 Hz, 1H), 6.43 (dd, J = 8.7, 2.5 Hz, 1H), 5.89 (s, 1H), 3.77 (s, 3H),
1.46 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.8, 162.6, 145.1, 143.4, 133.1, 132.8, 132.5, 132.1, 129.2, 124.7,
122.0, 118.9, 118.9, 114.5, 114.5, 114.4, 113.6, 106.5, 100.4, 55.3, 51.8, 28.9; IR (NaCl) 3330, 2970, 1632, 1584,
1526, 1473, 1420, 1382, 1289, 1221, 1179, 1130, 1040, 987, 874, 771, 683 cm−1; HRMS (EI) m/z calcd. for
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C20H20F6N2O2 [M] +: 434.1429, found: 434.1426; Rf (nꢀhexane/EtOAc 5/1): 0.52.
Analytic data of amidated benzamide products [(3a-3d, 3g, 3i-3q, 4a-4c, 4f),9 4e,8a (4g, 4i)8b] has been reported
earlier by our group.
General procedure for the amidation of aryl carbamates with p-toluenesulfonyl azide. To a
screw capped vial with a spinvane triangularꢀshaped Teflon stir bar were added aryl carbamate (5, 0.36 mmol), pꢀ
toluenesulfonyl azide (2a, 0.2 mmol), [IrCp*Cl2]2 (6.4 mg, 0.008 mmol, 4 mol %), AgNTf2 (12.4 mg, 0.032 mmol,
16 mol %), Cu(OAc)2 (3.6 mg, 0.02 mmol, 10 mol %) and 1,2ꢀdichloroethane (0.5 mL) under atmospheric
ο
conditions. The reaction mixture was stirred in a preꢀheated oil bath at 50 C for 12 h, filtered through a pad of
celite and then washed with EtOAc (10 mL × 3). Organic solvents were removed under reduced pressure and the
residue was purified by chromatography on silica gel (nꢀhexane/EtOAc) to give the desired product 6.
2-(4-Methylphenylsulfonamido)phenyl dimethyl carbamate (6a). White solid (53.6 mg, 80%); m.p.
127−129 °C; 1H NMR (400 MHz, CDCl3) δ 7.6 –7.58 (m, 2H), 7.51−7.45 (m, 1H), 7.2 −7.17 (m, 2H), 7.16−7.10
(m, 2H), 7.07 (s, 1H), 7.02−6.96 (m, 1H), 2.92 (d, J = 10.9 Hz, 6H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
151.7, 143.7, 143.6, 136.8, 129.5, 128.7, 127.0, 126.4, 125.9, 124.9, 122.6, 46.6, 46.4, 25.7, 24.9, 21.5; IR (NaCl)
3435, 1710, 1639, 1497, 1389, 1335, 1246, 1164, 1092, 919, 840, 814, 753, 665 cm−1; HRMS (EI) m/z calcd. for
C16H18N2O4S [M] +: 334.0987, found: 334.0986; Rf (nꢀhexane/EtOAc, 2/1): 0.30.
4-Methoxy-2-(4-methylphenylsulfonamido)phenyl dimethylcarbamate (6b). Yellow solid (60.3 mg,
83%); m.p. 109−111 °C; 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.3 Hz, 2H), 7.24−7.20 (m, 2H), 7.04 (d, J =
3.0 Hz, 1H), 6.94 (s, 1H), 6.88 (d, J = 8.9 Hz, 1H), 6.64 (dd, J = 8.9, 3.0 Hz, 1H), 3.75 (s, 3H), 2.92 (d, J = 10.8
13
Hz, 6H), 2.38 (s, 3H); C NMR (100 MHz, CDCl3) δ 157.2, 154.0, 143.8, 137.0, 136.6, 129.6, 127.1, 123.2,
111.9, 109.4, 55.7, 36.8, 36.4, 21.5; IR (NaCl) 3267, 2936, 1728, 1600, 1511, 1446, 1387, 1308, 1253, 1208,
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1159, 1066, 1038, 970, 854, 755, 667 cm−1; HRMS (EI) m/z calcd. for C17H20N2O5S [M]+: 364.1093, found:
364.1090; Rf (nꢀhexane/EtOAc, 2/1): 0.37.
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4-Chloro-2-(4-methylphenylsulfonamido)phenyl dimethyl carbamate (6c). Yellow solid (62.3 mg,
84%); m.p. 135−137 °C; 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 2.5 Hz, 1H), 7.35 (s,
1H), 7.22 (d, J = 8.5 Hz, 2H), 7.06 (dd, J = 8.7, 2.5 Hz, 1H), 6.92 (d, J = 8.7 Hz, 1H), 2.91 (d, J = 2.3 Hz, 6H),
2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 153.3, 144.0, 141.8, 136.2, 131.0, 130.0, 129.6, 127.0, 125.9, 123.9,
123.8, 36.8, 36.4, 29.6, 21.5; IR (NaCl) 3440, 1712, 1641, 1493, 1385, 1335, 1250, 1163, 1117, 1092, 939, 813,
675 cm−1; HRMS (EI) m/z calcd. for C16H17ClN2O4S [M]+: 368.0598, found: 368.0596; Rf (nꢀhexane/EtOAc, 3/1):
0.26.
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2-Isopropyl-6-(4-methylphenylsulfonamido)phenyl dimethyl carbamate (6d). Brown solid (41.8
mg, 55%); m.p. 84−86 °C; 1H NMR (400 MHz, CDCl3) δ 7.66−7.57 (m, 2H), 7.31−7.25 (m, 1H), 7.23−7.18 (m,
2H), 7.17−7.05 (m, 2H), 6.94 (s, 1H), 2.97 (s, 3H), 2.92 (s, 3H), 2.91−2.81 (m, 1H), 2.37 (s, 3H), 1.11 (d, J = 6.9
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Hz, 6H); C NMR (100 MHz, CDCl3) δ 153.7, 143.4, 142.0, 141.4, 137.1, 129.4, 127.2, 126.2, 123.9, 123.2,
37.0, 36.3, 27.7, 22.7, 21.5; IR (NaCl) 3443, 2966, 2105, 1643, 1474, 1400, 1325, 1164, 1092, 983 cm−1; HRMS
(EI) m/z calcd. for C19H24N2O4S [M]+: 376.1457, found: 376.1455; Rf (nꢀhexane/EtOAc, 3/1): 0.16.
5-Methyl-2-(4-methylphenylsulfonamido)phenyl dimethyl carbamate (6e). Light brown solid (37.7
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mg, 54%); m.p. 147−149 °C; H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.2 Hz, 1H),
7.23−7.16 (m, 2H), 6.98−6.90 (m, 1H), 6.88 (s, 1H), 6.81 (s, 1H), 2.92 (s, 3H), 2.86 (s, 3H), 2.37 (s, 3H), 2.27 (s,
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3H); C NMR (100 MHz, CDCl3) δ 153.7, 144.1, 143.5, 137.1, 136.9, 129.5, 127.1, 126.7, 125.9, 125.8, 123.1,
36.8, 36.4, 21.5, 20.9; IR (NaCl) 3269, 2926, 1729, 1597, 1509, 1448, 1407, 1384, 1334, 1263, 1165, 1114, 1092,
1019, 910, 882, 756, 527 cm−1; HRMS (EI) m/z calcd. for C17H20N2O4S [M]+: 348.1144, found: 348.1147; Rf (nꢀ
hexane/EtOAc, 2/1): 0.29.
2-(4-Methylphenylsulfonamido)phenyl diethylcarbamate (6f). White solid (64.2 mg, 89%); m.p.
103−105 °C; 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.4 Hz, 2H), 7.52–7.42 (m, 1H), 7.20 (d, J = 7.9 Hz, 2H),
7.17−7.05 (m, 2H), 7.03−6.98 (m, 1H), 6.95 (s, 1H), 3.32 (q, J = 7.2 Hz, 2H), 3.22 (q, J = 7.1 Hz, 2H), 2.37 (s,
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3H), 1.16 (dt, J = 11.8, 7.2 Hz, 6H); C NMR (100 MHz, CDCl3) δ 153.0, 143.9, 143.6, 136.9, 129.5, 128.9,
127.0, 126.5, 126.0, 125.3, 122.5, 42.5, 42.0, 21.5, 14.2, 13.3; IR (NaCl) 3264, 3067, 2976, 2935, 2877, 1918,
1723, 1600, 1498, 1427, 1336, 1247, 1164, 1093, 1043, 961, 814, 753, 666, 568 cm−1; HRMS (EI) m/z calcd. for
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C18H22N2O4S [M]+: 362.1300, found: 362.1302; Rf (nꢀhexane/EtOAc, 2/1): 0.33.
(4-Methylphenylsulfonamido)phenyl ethyl(meth-yl) carbamate (6g). White solid (53.7 mg, 77%);
m.p. 119−121 °C; 1H NMR (400 MHz, CDCl3) δ 7.63−7.55 (m, 2H), 7.52−7.43 (m, 1H), 7.19 (d, J = 8.6 Hz, 2H),
7.16−7.08 (m, 2H), 7.08−6.91 (m, 2H), 3.29 (dq, J = 24.6, 7.2 Hz, 2H), 2.88 (d, J = 26.2 Hz, 3H), 2.37 (s, 3H),
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1.15 (td, J = 7.1, 4.3 Hz, 3H); C NMR (100 MHz, CDCl3) δ 153.4, 153.2, 144.0, 143.9, 143.7, 143.6, 136.8,
129.5, 128.9, 128.8, 127.0, 127.0, 126.5, 126.5, 126.0, 125.9, 125.4, 125.1, 122.6, 44.3, 44.1, 34.3, 33.8, 21.5,
13.3, 12.4; IR (NaCl) 3444, 2087, 1644, 1498, 1402, 1335, 1304, 1246, 1163, 1091, 752, 665 cm−1; HRMS (EI)
m/z calcd. for C17H20N2O4S [M]+: 348.1144, found: 348.1140; Rf (nꢀhexane/EtOAc, 3/1): 0.22.
2-(4-Methylphenylsulfonamido)phenylpyrrolidin-e-1-carboxylate (6h). Bright yellow solid (53.5 mg,
74%); m.p. 170−172 °C; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H), 7.52−7.45 (m, 1H), 7.19 (d, J =
8.0 Hz, 2H), 7.15−7.10 (m, 2H), 7.09 (s, 1H), 7.06−6.99 (m, 1H), 3.42−3.35 (m, 2H), 3.34−3.28 (m, 2H), 2.37 (s,
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3H), 1.92 (s, 4H); C NMR (100 MHz, CDCl3) δ 151.7, 143.7, 143.6, 136.8, 129.5, 128.7, 127.0, 126.4, 125.9,
124.9, 122.6, 46.6, 46.4, 25.7, 24.9, 21.5; IR (NaCl) 3266, 2976, 2880, 1727, 1600, 1498, 1414, 1337, 1248,
1120, 1104, 1092, 1058, 1018, 916, 814, 754, 667 cm−1; HRMS (EI) m/z calcd. for C18H20N2O4S [M]+: 360.1144,
found: 360.1145; Rf (nꢀhexane/EtOAc, 2/1): 0.31.
General procedure for the amidation of chelate group-containing arenes with p-
toluenesulfonyl azide. To a screw capped vial equipped with a spinvane triangularꢀshaped Teflon stir bar were
added chelate groupꢀcontaining arene (7 or 9, 0.2 mmol), pꢀtoluenesulfonyl azide (2a, indicated molar ratio in
Scheme 5 or 6), [IrCp*Cl2]2 (6.4 mg, 0.008 mmol, 4 mol %), AgNTf2 (12.4 mg, 0.032 mmol, 16 mol %) and 1,2ꢀ
dichloroethane (0.5 mL) under atmospheric conditions. [Substrate (9b-9f) was used in the presence of NaOAc
(3.3 mg, 0.040 mmol, 20 mol %)]. The reaction mixture was stirred in a preꢀheated oil bath at the indicated
ο
temperature (50 οC or 80 C) for 12 h. The reaction mixture was cooled to room temperature, filtered through a
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pad of celite and then washed with EtOAc (10 mL × 3). Organic solvents were removed under reduced pressure
and the residue was purified by chromatography on silica gel (nꢀhexane/EtOAc) to give the desired product 8 or
10.
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(E)-N-[2-{1-(Methoxyimino)ethyl}phenyl]-4-meth-ylbenzenesulfonamide (8a). Light yellow solid
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(32.5 mg, 51%); m.p. 127−129 °C; H NMR (400 MHz, CDCl3) δ 10.75 (s, 1H), 7.63 (dd, J = 8.1, 1.3 Hz, 1H),
7.58 (d, J = 8.3 Hz, 2H), 7.33−7.22 (m, 2H), 7.18 (d, J = 8.0 Hz, 2H), 7.08 (td, J = 7.7, 1.3 Hz, 1H), 4.06 (s, 3H),
2.35 (s, 3H), 2.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 155.9, 143.4, 136.4, 135.8, 129.7, 129.4, 128.4, 127.1,
124.5, 124.1, 121.8, 62.6, 21.5, 13.1; IR (NaCl) 3451, 3175, 2974, 2934, 2852, 2818, 1603, 1498, 1371, 1160,
1091, 919, 565 cm−1; HRMS (EI) m/z calcd. for C16H18N2O3S [M]+: 318.1038, found: 318.1036; Rf (nꢀ
hexane/EtOAc, 3/1): 0.35.
(E)-4-Methyl-N-[2-{1-(2-tosylhydrazono)ethyl}phenyl]benzenesulfonamide (8b). White solid (65.0
mg, 73%); m.p. 181−183 °C; 1H NMR (400 MHz, CDCl3) δ 10.51 (s, 1H), 8.08−8.00 (m, 3H), 7.72 (dd, J = 8.4,
1.2 Hz, 1H), 7.57 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.32−7.20 (m, 2H), 7.15 (d, J = 8.0 Hz, 2H),
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7.09−7.00 (m, 1H), 2.42 (s, 3H), 2.33 (s, 3H), 1.94 (s, 3H); C NMR (100 MHz, CDCl3) δ 154.6, 145.0, 143.4,
136.5, 136.1, 134.5, 130.4, 130.2, 129.3, 128.6, 128.3, 127.3, 125.4, 124.0, 122.6, 21.7, 21.5, 14.9; IR (NaCl)
3204, 3065, 2924, 2361, 2339, 1599, 1496, 1400, 1338, 1164, 1091, 913, 815, 668 cm−1; HRMS (EI) m/z calcd.
for C22H23N3O4S2 [M]+: 457.1130, found: 457.1126; Rf (nꢀhexane/EtOAc, 2/1): 0.18.
4-Methyl-N-[2-(pyridin-2-yl)phenyl]benzenesulfonamide (8c). Yellow solid(46.1 mg, 71%); m.p.
106−108 °C; 1H NMR (400 MHz, CDCl3) δ 12.14 (s, 1H), 8.63−8.56 (m, 1H), 7.80−7.65 (m, 2H), 7.52 (dd, J =
7.9, 1.5 Hz, 1H), 7.42−7.29 (m, 4H), 7.24 (ddd, J = 7.5, 4.9, 1.1 Hz, 1H), 7.15 (td, J = 7.6, 1.3 Hz, 1H), 6.96 (d, J
= 8.7 Hz, 2H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.1, 147.4, 142.9, 137.4, 136.8, 136.4, 130.1, 129.1,
128.5, 127.5, 126.7, 124.7, 123.4, 122.2, 122.1, 21.4; IR (NaCl) 3448, 2098, 1640, 1592, 1498, 1474, 1431, 1337,
1184, 1091, 927, 754, 657 cm−1; HRMS (EI) m/z calcd. for C18H16N2O2S [M]+: 324.0932, found: 324.0934; Rf (nꢀ
hexane/EtOAc, 5/1): 0.25.
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N-[2-(1H-Pyrazol-1-yl)phenyl]-4-methylbenzenesulfonamide (8d). White solid (46.4 mg, 74%); m.p.
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94−96 °C; H NMR (400 MHz, CDCl3) δ 10.04 (s, 1H), 7.88−7.63 (m, 2H), 7.43−7.23 (m, 4H), 7.23−7.10 (m,
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2H), 7.01 (d, J = 8.0 Hz, 2H), 6.35 (s, 1H), 2.30 (s, 3H); C NMR (100 MHz, CDCl3) δ 143.2, 141.1, 136.1,
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131.3, 130.2, 129.3, 129.3, 127.9, 126.6, 125.9, 125.4, 121.8, 107.2, 21.4; IR (NaCl) 3443, 3428, 2922, 1920,
1735, 1597, 1505, 1434, 1390, 1333, 1166, 1092, 1052, 944, 910, 800, 764, 728, 675, 566 cm−1; HRMS (EI) m/z
calcd. for C16H15N3O2S [M]+: 313.0885, found: 313.0882; Rf (nꢀhexane/EtOAc, 5/1): 0.27.
N-[2-(4,5-Dihydrooxazol-2-yl)phenyl]-4-methylbenzenesulfonamide (8e). Light yellow solid
(53.8mg, 85%); m.p. 195−197 °C; 1H NMR (400 MHz, CDCl3) δ 12.33 (s, 1H), 7.82–7.70 (m, 3H), 7.64 (dd, J =
8.5, 1.1 Hz, 1H), 7.38–7.29 (m, 1H), 7.20 (d, J = 8.4 Hz, 2H), 6.99 (td, J = 7.6, 1.1 Hz, 1H), 4.35 (t, J = 9.7 Hz,
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2H), 4.13 (t, J = 9.3 Hz, 2H), 2.35 (s, 3H); C NMR (100 MHz, CDCl3) δ 164.5, 143.5, 139.1, 136.9, 132.3,
129.5, 129.3, 127.2, 122.2, 117.8, 113.5, 66.4, 54.4, 21.5; IR (NaCl) 3082, 3062, 2943, 2919, 2887, 2853, 1631,
1598, 1584, 1503, 1443, 1337, 1259, 1159, 1066, 942 cm−1; HRMS (EI) m/z calcd. for C16H16N2O3S [M]+:
316.0882, found: 316.0882; Rf (nꢀhexane/EtOAc, 5/1): 0.24.
4-Methyl-N-[2-(pyridin-2-ylmethyl)phenyl]benzenesulfonamide (8f). Light brown oil (52.8 mg, 78%);
1H NMR (400 MHz, CDCl3) δ 11.34 (s, 1H), 8.66−8.29 (m, 1H), 7.73−7.67 (m, 2H), 7.60 (td, J = 7.7, 1.8 Hz,
1H), 7.53 (dd, J = 8.0, 1.3 Hz, 1H), 7.23−7.10 (m, 6H), 7.02 (td, J = 7.5, 1.3 Hz, 1H), 3.63 (s, 2H), 2.37 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.3, 148.6, 143.1, 138.4, 137.9, 136.5, 132.3, 130.2, 129.6, 128.0, 126.8, 125.3,
124.6, 122.9, 122.0, 41.4, 21.5; IR (NaCl) 3064, 2956, 2923, 2853, 1920, 1595,1571, 1494, 1476, 1438, 1335,
1289, 1274, 1240, 1162, 1107, 1093, 1019, 939, 814, 758, 660 cm−1; HRMS (EI) m/z calcd. for C19H18N2O2S
[M]+: 338.1089, found: 338.1089; Rf (nꢀhexane/EtOAc, 5/1): 0.30.
N-[2-(4-Methylphenylsulfonamido)phenyl]acetamide (8g). White solid (54.8 mg, 90%); m.p. 142−144
°C; 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 7.5 Hz, 2H), 7.50 (s, 1H),
7.21 (d, J = 7.6 Hz, 2H), 7.16 (t, J = 7.9 Hz, 1H), 6.97 (t, J = 7.9 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 2.39 (s, 3H),
2.08 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 169.8, 144.0, 135.8, 133.7, 129.6, 127.8, 127.7, 127.3, 127.2, 125.6,
123.7, 24.0, 21.5; IR (NaCl) 3326, 3254, 3129, 2925, 2868, 1668, 1598, 1528, 1496, 1400, 1307, 1160, 1091, 925,
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814, 665 cm−1; HRMS (EI) m/z calcd. for C15H16N2O3S [M]+: 304.0882, found: 304.0879; Rf (nꢀhexane/EtOAc,
5/1): 0.28.
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N-[2-(4-Methylphenylsulfonamido)phenyl]pivalamide (8h). Light brown solid (52.0mg, 75%); m.p.
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186−188 °C; H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 7.87−7.76 (m, 1H), 7.53 (dd, J = 8.3, 1.3 Hz, 2H),
7.25−7.14 (m, 3H), 6.95−6.86 (m, 2H), 6.67−6.56 (m, 1H), 2.41 (s, 3H), 1.32 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 177.8, 144.0, 135.5, 135.1, 129.5, 128.3, 128.1, 127.5, 126.8, 124.9, 123.7, 39.8, 27.5, 21.5; IR (NaCl)
3419, 3361, 3131, 2965, 2873, 1660, 1597, 1524, 1496, 1450, 1401, 1331, 1159, 1091, 927, 813, 763, 717 cm−1;
HRMS (EI) m/z calcd. for C18H22N2O3S [M]+: 346.1351, found: 346.1348; Rf (nꢀhexane/EtOAc, 5/1): 0.32.
4-Methyl-N-[2-(2-oxopyrrolidin-1-yl)phenyl]benzenesulfonamide (8i). White solid (56.8 mg, 86%);
m.p. 167−169 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 7.58−7.48 (m, 3H), 7.33−7.16 (m, 4H), 7.04 (dd, J
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= 7.8, 1.8 Hz, 1H), 3.29 (t, J = 7.0 Hz, 2H), 2.47 (t, J = 8.1 Hz, 2H), 2.39 (s, 3H), 1.84 (p, J = 7.6 Hz, 2H); C
NMR (100 MHz, CDCl3) δ 174.9, 143.2, 138.0, 133.5, 130.9, 129.3, 129.2, 127.6, 127.3, 126.6, 122.8, 50.5, 31.6,
21.4, 18.5; IR (NaCl) 3068, 2979, 2923, 2898, 1670, 1598, 1497, 1409, 1332, 1164, 1092, 912, 816, 764 cm−1;
HRMS (ESI) m/z calcd. for C17H18N2O3S [M+Na]+: 353.0936, found: 353.0930; Rf (nꢀhexane/EtOAc, 5/1): 0.30.
N-[2-(Benzo[d]oxazol-2-yl)phenyl]-4-methylbenzenesulfonamide (10a). White solid (58.4 mg, 80%);
m.p. 161−164 °C; 1H NMR (400 MHz, CDCl3) δ 11.66 (s, 1H), 8.03 (dd, J = 7.9, 1.6 Hz, 1H), 7.79−7.73 (m, 1H),
7.70 (td, J = 8.3, 1.5 Hz, 3H), 7.52−7.45 (m, 1H), 7.39−7.27 (m, 3H), 7.11−7.01 (m, 3H), 2.22 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 161.5, 149.2, 143.7, 140.6, 138.2, 136.6, 132.6, 129.5, 128.5, 127.3, 125.8, 125.1, 123.2,
120.0, 119.0, 113.7, 110.5, 21.5; IR (NaCl) 3425, 3123, 2921, 1618, 1587, 1545, 1497, 1476, 1452, 1429, 1345,
1268, 1247, 1132, 1091, 1055, 946, 914, 895, 809, 759, 675 cm−1; HRMS (EI) m/z calcd. for C20H16N2O3S [M]+:
364.0882, found: 364.0879; Rf (nꢀhexane/EtOAc, 4/1): 0.35.
N-[1-(Isoquinolin-1-yl)naphthalen-2-yl]-4-methylbenzenesulfonamide (10b). Light yellow solid
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(69.0 mg, 81%); m.p. 213−215 °C; H NMR (400 MHz, CDCl3) δ 8.65 (dd, J = 5.6, 3.5 Hz, 1H), 8.33 (s, 1H),
8.07−7.92 (m, 2H), 7.89−7.80 (m, 2H), 7.74 (d, J = 5.7 Hz, 1H), 7.60 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.37 (ddd, J
= 8.2, 6.8, 1.3 Hz, 1H), 7.14 (ddd, J = 8.4, 6.8, 1.4 Hz, 1H), 7.06 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 6.99 (d, J = 8.3
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Hz, 2H), 6.92−6.87 (d, 1H), 6.73 (d, J = 8.4, 1.2 Hz, 1H), 6.51 (d, J = 8.1 Hz, 2H), 2.00 (s, 3H); C NMR (100
MHz, CDCl3) δ 156.2, 142.9, 142.2, 136.3, 136.1, 133.0, 132.3, 131.3, 130.1, 130.1, 129.0, 128.1, 127.6, 127.3,
127.1, 126.8, 126.6, 126.3, 126.1, 125.6, 123.8, 121.1, 21.3; IR (NaCl) 3449, 2097, 1632, 1605, 1475, 1388, 1336,
1297, 1239, 1162, 1115, 1049, 814, 602 cm−1; HRMS (ESI) m/z calcd. for C26H20N2O2S [M+H]+: 425.1324,
found: 425.1324; Rf (nꢀhexane/EtOAc, 4/1): 0.32.
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N-[2-(Isoquinolin-1-yl)phenyl]-4-methylbenzenesulfonamide (10c). White solid (62.5 mg, 84%); m.p.
158−161 °C; 1H NMR (400 MHz, CDCl3) δ 9.63 (s, 1H), 8.51 (d, J = 5.7 Hz, 1H), 7.88−7.84 (m, 1H), 7.83−7.76
(m, 1H), 7.68−7.58 (m, 2H), 7.53−7.41 (m, 2H), 7.40−7.23 (m, 3H), 6.91 (d, J = 8.3 Hz, 2H), 6.42 (d, J = 8.4 Hz,
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2H), 1.83 (s, 3H); C NMR (100 MHz, CDCl3) δ 157.3, 142.5, 140.8, 137.2, 135.6, 135.3, 131.6, 131.0, 130.1,
129.8, 128.8, 127.6, 127.2, 126.9, 126.8, 126.6, 126.0, 125.2, 120.4, 21.1; IR (NaCl) 3426, 3058, 1621, 1554,
1492, 1394, 1379, 1337, 1266, 1183, 1165, 1091, 832, 813, 759, 690 cm−1; HRMS (EI) m/z calcd. for
C22H18N2O2S [M]+: 374.1089, found: 374.1088; Rf (nꢀhexane/EtOAc, 4/1): 0.36.
N-[5-Bromo-2-(isoquinolin-1-yl)phenyl]-4-methylbenzenesulfonamide (10d). White solid (80.4 mg,
89%); m.p. 160−162 °C; 1H NMR (400 MHz, CDCl3) δ 9.71 (s, 1H), 8.51 (d, J = 5.7 Hz, 1H), 8.03 (d, J = 1.9 Hz,
1H), 7.82 (d, J = 1.0 Hz, 1H), 7.71−7.65 (m, 1H), 7.64 (dd, J = 5.8, 0.9 Hz, 1H), 7.46−7.34 (m, 3H), 7.24 (d, J =
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8.2 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H), 6.48−6.44 (m, 2H), 1.85 (s, 3H); C NMR (100 MHz, CDCl3) δ 156.3,
142.9, 140.8, 137.2, 136.7, 135.4, 132.7, 130.3, 130.2, 129.6, 128.9, 128.4, 127.1, 127.1, 126.7, 126.5, 126.0,
123.3, 120.8, 21.1, IR (NaCl) 3438, 1621, 1593, 1550, 1483, 1452, 1375, 1333, 1245, 1165, 1109, 1091, 975, 920,
893, 826, 736, 696, 621 cm−1; HRMS (ESI) m/z calcd. for C22H17BrN2O2S [M+Na]+: 475.0092, found: 475.0082;
Rf (nꢀhexane/EtOAc, 4/1): 0.31.
N-[5-Formyl-2-(isoquinolin-1-yl)phenyl]-4-methylbenzenesulfonamide (10e). White solid (66.6 mg,
83%); m.p. 156−158 °C; 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 9.70 (s, 1H), 8.57 (d, J = 5.7 Hz, 1H), 8.33
(s, 1H), 7.90−7.81 (m, 2H), 7.74−7.66 (m, 2H), 7.55 (d, J = 7.9 Hz, 1H), 7.48−7.33 (m, 2H), 6.95 (d, J = 8.4 Hz,
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2H), 6.47 (d, J = 8.5 Hz, 2H), 1.87 (s, 3H); C NMR (100 MHz, CDCl3) δ 191.3, 155.9, 142.9, 140.9, 137.2,
137.2, 136.4, 136.1, 135.4, 132.3, 130.4, 129.7, 129.0, 127.4, 127.2, 126.5, 126.0, 124.5, 121.3, 21.1; IR (NaCl)
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3381, 3234, 2847, 1698, 1619, 1568, 1498, 1374, 1334, 1274, 1215, 1184, 1091, 877, 812, 691 cm−1; HRMS (ESI)
m/z calcd. for C23H18N2O3S [M+Na]+: 425.0936 , found: 425.0920; Rf (nꢀhexane/EtOAc, 3/1): 0.35.
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Methyl-4-(isoquinolin-1-yl)-3-(4-methylphenylsulfonamido)benzoate (10f). White solid (80.5 mg,
93%); m.p. 160−162 °C; 1H NMR (400 MHz, CDCl3) δ 9.63 (s, 1H), 8.55 (d, J = 5.7 Hz, 1H), 8.50 (dd, J = 1.8,
0.4 Hz, 1H), 7.97 (dd, J = 8.0, 1.7 Hz, 1H), 7.84 (dt, J = 8.3, 1.0 Hz, 1H), 7.72−7.61 (m, 2H), 7.49−7.30 (m, 3H),
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6.98−6.88 (m, 2H), 6.44 (dd, J = 8.6, 0.7 Hz, 2H), 3.99 (s, 3H), 1.85 (s, 3H); C NMR (100 MHz, CDCl3) δ
166.3, 156.4, 143.0, 141.0, 137.4, 135.8, 135.6, 135.1, 131.9, 131.7, 130.5, 129.1, 128.8, 127.4, 127.3, 126.9,
126.7, 126.4, 126.2, 121.3, 52.7, 21.3; IR (NaCl) 3429, 3234, 3045, 2964, 1723, 1621, 1585, 1552, 1498, 1437,
1379, 1336, 1298, 1236, 1166, 1117, 1090, 995, 768, 697 cm−1; HRMS (EI) m/z calcd. for C24H20N2O4S [M]+:
432.1144, found: 432.1142; Rf (nꢀhexane/EtOAc, 4/1): 0.21.
Acknowledgment. This paper is dedicated to Professor Teruaki Mukaiyama in celebration of the 40th
anniversary of the Mukaiyama aldol reaction. This research was supported by the Institute of Basic Science
(IBS).
1
Supporting Information Available. Copies of H and 13C NMR spectra data for all new compounds. This
material is available free of charge via the Internet at http://pubs.acs.org.
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