Rh-catalyzed transannulation of N-tosyl-1,2,3-triazoles with terminal alkynes

Article abstract of DOI:10.1021/ol2014347

The first transannulation of 1,2,3-triazoles with terminal alkynes into pyrroles is reported. The reaction proceeds in the presence of a Rh ₂(oct)₄/AgOCOCF₃ binary catalyst system providing a straightforward approach to 1,2,4-trisubstituted pyrroles in good to excellent yields.

Full text of DOI:10.1021/ol2014347

S 1
Supporting Information for
Rh-Catalyzed Transannulation of N-Tosyl-1,2,3-Triazoles with
Terminal Alkynes
Buddhadeb Chattopadhyay, and Vladimir Gevorgyan*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
E-mail: vlad@uic.edu
Contents:
General Information……………………………………………………………… S2
Preparation of 1,2,3-triazoles…………………………………………………….. S2
Preparation of 4-phenyl-1-(p-tolylsulfonodithioyl)-1H-1,2,3-triazole…………… S2
Preparation of ethyl 4-(1-tosyl-1H-1,2,3-triazol-4-yl)benzoate………………….. S2
Preparation of 4-p-tolyl-1-tosyl-1H-1,2,3-triazole……………………………….. S3
Preparation of 4-(4-bromophenyl)-1-tosyl-1H-1,2,3-triazole…………………….. S3
Preparation of 4-butyl-1-tosyl-1H-1,2,3-triazole…………………………………. S3
Preparation of ethyl 1-tosyl-1H-1,2,3-triazole-4-carboxylate……………………. S4
Preparation of 1-tosyl-1H-1,2,3-triazole………………………………………….. S4
Preparation of alkynes…………………………………………………………….. S5
Transannulation Reaction…………………………………………………………. S5
Optimization of the Transannulation Reaction……………………………………. S5
General Procedure for the Transannulation Reaction…………………………….. S6
Semi-one-pot method for the Transannulation Reaction…………………………. S6
Preparation of deuteriated o-tollylacetylene……………………………………… S7
D-Labeling Experiment…………………………………………………………… S7
Compound Characterization data…………………………………………………. S8
References………………………………………………………………………… S22
Copies of NMR spectra…………………………………………………………… S23

S 2
General Information
NMR spectra were recorded on Bruker Avance DRX-500 (500 MHz) or DPX-400 (400
MHz) instruments. LRMS and HRMS analyses were performed on Micromass 70 VSE mass
spectrometer. GC/MS analysis was performed on a Hewlett Packard Model 6890 GC
interfaced to a Hewlett Packard Model 5973 mass selective detector (15 m x 0.25 mm
capillary column, HP-5MS). Column chromatography was carried out employing
Silicycle silica gel (Kieselgel 60, 63-200 μm). Pre-coated silica gel plates F-254 were
used for thin-layer analytical chromatography. Anhydrous solvents were purchased from
Aldrich and stored over calcium hydride. n-Hexane was dried twice over Na and stored
for a week. Reactions were performed in oven-dried glassware under inert atmosphere unless
otherwise stated. Alkynes and Rh-catalysts were commercially available and purchased
from Sigma Aldrich and used immediately as received.
Preparation of 1,2,3-triazoles:
Preparation of 4-phenyl-1-(p-tolylsulfonodithioyl)-1H-1,2,3-triazole:
Ph
10% CuI, 1.2 equiv 2,6 lutidine
TsN3
Ph
+
N
CHCl3 (0.5 M), 0 oC, 12 h
N
Ts
N
Ph
N
Compound 1a: This compound was prepared according to the previously
reported copper-catalyzed azide-alkyne cycloaddition (CuAAC) procedure.1
N
Ts
N
Preparation of ethyl 4-(1-tosyl-1H-1,2,3-triazol-4-yl)benzoate:
Ts
10% CuI, 1.2 equiv 2,6 lutidine
N
+
TsN3
CO2Et
EtO2C
CHCl3 (0.5 M), 0 oC, 12 h
N
N
CO2Et
Compound 1b: To a stirred mixture of alkyne (2.2 g, 12.0 mmol), p-
toluenesulfonyl azide (1.9 g, 10.0 mmol), and CuI (190 mg, 10 mol %)
in 50 mL chloroform, 2,6-lutidine (1.4 mL, 12.0 mmol) was added at 0
ºC under inert atmosphere. Reaction mixture was stirred for 12 h at −5-0
N
N
Ts
N
ºC until judged complete by TLC analysis, and quenched with saturated aq. NH4Cl

S 3
solution (40 mL). The aqueous layer was extracted with CH2Cl2 (3 × 50 mL) and the
combined organic fractions were sequentially washed with water and brine, and dried
(Na2SO4). After removal of solvents in vacuo, the residue was purified by flash
chromatography (ethyl acetate: hexane = 1:9) to afford the corresponding 1,2,3-triazole
1b 2.2 g (60%) as a white solid.
Preparation of 4-p-tolyl-1-tosyl-1H-1,2,3-triazole:
Ts
10% CuI, 1.2 equiv 2,6 lutidine
N
+
TsN3
CHCl3 (0.5 M), 0 oC, 12 h
N
N
Compound 1c: This compound was prepared according to the previously
reported copper-catalyzed azide-alkyne cycloaddition (CuAAC) procedure.1
N
N
Ts
N
Preparation of 4-(4-bromophenyl)-1-tosyl-1H-1,2,3-triazole:
Ts
10% CuI, 1.2 equiv 2,6 lutidine
N
N
+
TsN3
Br
Br
CHCl3 (0.5 M), 0 oC, 12 h
N
Br
Compound 1d: This compound was prepared according to the previously
reported copper-catalyzed azide-alkyne cycloaddition (CuAAC)
procedure.1
N
N
Ts
N
Preparation of 4-butyl-1-tosyl-1H-1,2,3-triazole:
Ts
10% CuI, 1.2 equiv 2,6 lutidine
CHCl3 (0.5 M), 0 oC, 12 h
N
N
+
TsN3
N
Compound 1e: To a stirred mixture of alkyne (985.7 mg, 12.0 mmol), p-
toluenesulfonyl azide (1.9 g, 10.0 mmol), and CuI (190 mg, 10 mol %) in 50
mL chloroform, 2,6-lutidine (1.4 mL, 12.0 mmol) was added at 0 ºC under inert
N
N
Ts
N
atmosphere. Reaction mixture was stirred for 12 hours at −5-0 ºC until judged complete
by TLC analysis, and quenched with saturated aq. NH4Cl solution (40 mL). The aqueous
layer was extracted with CH2Cl2 (3 × 50 mL) and the combined organic fractions were

S 4
sequentially washed with water and brine, and dried (Na2SO4). After removal of solvents
in vacuo, the residue was purified by flash chromatography (ethyl acetate: hexane = 1:9)
to afford the corresponding 1,2,3-triazole 1e 1.74 g (62%) as a pale yellow oil; (1H NMR
(500 MHz, CDCl3): δ 7.94 (d, J=8.44 Hz, 2 H), 7.62 (s, 1 H), 7.33 (d, J=8.07 Hz, 2 H),
2.61 - 2.77 (m, 2 H), 2.42 (s, 3 H), 1.48 - 1.71 (m, 2 H), 1.15 - 1.44 (m, 2 H), 0.89 (t,
13
J=7.34 Hz, 3 H); C NMR (126 MHz, CDCl3): δ 153.4, 146.3, 137.9, 133.2, 130.1,
128.6, 30.6, 25.3, 22.2, 21.8, 13.6.
Preparation of ethyl 1-tosyl-1H-1,2,3-triazole-4-carboxylate:
CO2Et
CO2Et
sealed tube
TsCl, DIPEA
CO2Et
+
N3
Si
N
105 oC, 4 days
28%
N
HN
DCM, RT, 12 h
45%
N
N
Ts
N
CO2Et
N
Compound 1f: A mixture of ethylpropiolate (2.5 g, 25.50 mmol)
N
trimethylsilyl azide (7.3 g, 63.75 mmol) was heated in a sealed tube at 105
Ts
N
oC for four days. The reaction mixture was cooled and ethanol was added dropwise with
stirring on ice bath. The solid formed was allowed to stand for 30 min and ether was
added. The solid was filtered off, washed with ether and hexane to give the pure NH-
triazole in 28% yield. The product was pure enough for further reaction. To p-
toluenesulfonyl chloride (1.0 g, 5.31 mmol) dissolved in dichloromethane (50 mL),
DIPEA (2.2 g, 17.25 mmol) was added at room temperature, and the reaction solution
was stirred for a few minutes. After the addition of the 4-ethylcarboxylate-1H-1,2,3-
triazole (500 mg, 3.54 mmol), stirring at room temperature was continued for 12 h before
the solvent was removed in vacuo. Flash chromatography (ethyl acetate: hexane = 1:9)
provided 450 mg of 1f (45%) as white solid.
Preparation of 1-tosyl-1H-1,2,3-triazole:
TsCl, DIPEA
N
N
DCM, RT, 22 h
82%
HN
N
N
Ts
N
Compound 1g: This compound was prepared according to the earlier
published procedure.2
N
N
Ts
N

S 5
Preparation of alkynes:
Alkynes such as 1-ethynyl-2,4,6-trimethylbenzene,3 1-ethynyl-2,3-dimethylbenzene,4 1-
ethynyl-3,4-dimethylbenzene,4 1-ethynyl-2-isopropylbenzene4 were prepared according
to the published procedures.
Transannulation Reaction:
Optimization of the transannulation reactiona
Ph
Ph
Rh-cat.; additive
N
+
N
solvent, 70 oC, 12 h
N
N
Ts
Ts
4a
1a
#
catalyst
(2.5%)
Lewis acid
(5.0%)
solvent
(0.06M)
yield (%)b
Rh2(OAc)4
Rh2(pfb)4
Rh2(dosp)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
1
AgOCOCF3
AgOCOCF3
Al(OTf)3
toluene
toluene
toluene
toluene
hexane
hexane
hexane
hexane
hexane
hexane
DCM
NR
NR
63
2
3
4
AgOCOCF3
AgOCOCF3
-
53
5
67
NRc
NR
NR
NR
NR
NR
NR
NR
Dce.d
Dce.
6
7
AgOTf
8
CsF
9
Zn(OTf)2
Y(OTf)2
10
11
12
13
14
15
AgOCOCF3
AgOCOCF3
AgOCOCF3
CF3SO3H
CF3CO2H
DCE
THF
hexane
hexane
aAll reactions were performed at 70 oC with 0.2 mmol of triazoles using 1.5 equiv of alkynes;
bIsolated yield; cNR = No Reaction; dDce. = Decomposition.

S 6
General Procedure for the Transannulation:
R
2.5 mol % Rh2(oct)4
R
5.0 mol % AgOCOCF3
R1
N
+
N
R1
0.06 M, 70 oC, 3-20 h
Ts
N
N
Ts
4
1
In a glovebox, 5 mL Weaton microreactor was charged with triazole 1 (0.20 mmol),
Rh2(oct)4 (3.9 mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by alkyne (1.5
equiv). The microreactor was capped with Teflon pressure cap and placed into pre-heated
aluminum block at 70 oC. The reaction mixture was stirred for 3-20 h (as judged by TLC
analysis). After completion, hexane was removed under reduced pressure and
chromatographic separation with silica gel gave products 4.
Semi-one-pot method for the Transannulation Reaction
1) 10% CuI, 1.2 equiv lutidine
0.5 M CHCl3, 0 oC, 12 h
TsN3
2) 2.5% Rh2(oct)4
N
OMe
5.0% AgOCOCF3
70 oC, 15 h
Ts
4p
1.5 equiv
OMe
59% over two steps
In a glovebox, 5 mL standard Weaton microreactor was charged with CuI (3.8 mg, 10
mol %), tosyl azide (40 mg, 0.2 mmol), p-tollylacetylene (24.4 mg, 0.21 mmol) and 2,6-
lutidine (25.72 mg, 0.24 mmol). The vial capped and dry chloroform (0.4 mL, 0.5 M) was
o
added outside the glovebox. The reaction mixture was stirred for 12 h at 0 C. After
completion, the reaction mixture was passed through a short pad of silica and dried under
reduced pressure to give the crude triazole. To this crude mixture, rhodium(II) octanoate
dimer (3.9 mg 2.5 mol %), AgOCOCF3 (2.2 mg, 5.0 mol %) and 1-ethynyl-2-methyl-4-
methoxybenzene (43.8 mg, 0.3 mmol) and dry hexane (3 mL, 0.06 M) were added. The
resulting mixture was placed into pre-heated aluminum block at 70 °C for 15 h. After
completion, hexane was removed under reduced pressure and chromatographic separation

S 7
with silica gel (ethyl acetate: hexane = 2:98) gave product 50.9 mg of 4p (59%) over two
steps.
Preparation of deuteriated o-tollyl acetylene
(i) Hexane, -78 oC
n-BuLi (0.9 equiv)
H
D
(ii) CD3OD (2.5 equiv)
Yield: 77%, 66% D
To a 50 mL flame-dried two-necked flask equipped with a stir bar, rubber septum, and T-
shaped stopcock with argon filled balloon were added anhydrous hexane (30 mL) and o-
tollylacetylene (0.58 g, 5 mmol). The solution was cooled to -78 ºC in a dry ice/acetone
bath while stirring and 0.42 mL of n-BuLi solution (0.90 equiv, 2.5 M in hexane) was
added slowly dropwise. After 10 minutes, 0.51 mL of methanol-d4 (2.5 equiv, 99.5% D)
were added and the reaction was stirred for 20 minutes at -78 ºC. After warming to room
temperature, the solvent was removed under reduced pressure and the residue filtered
through a short silica gel column (hexane:ether = 9:1 as eluent) affording 0.45 g of
1
deuteriated o-tollyl acetylene (77% yield, 66% D) as a yellow oil. H NMR (500 MHz,
CDCl3): δ 7.50 (d, J=7.70 Hz, 1 H), 7.21 - 7.32 (m, 2 H), 7.18 (d, J=7.70 Hz, 1 H), 2.49
(s, 3 H).
D-Labeling Experiment
Ph
Ph
D
2.5% Rh2(oct)4, 5% AgOCOCF3
0.06 M Hexane, 70 oC, 12 h
66% D
N
D
+
N
N
N
Ts
Ts
66% D
1a
Yield: 63%
4a-d
In a glovebox, 5 mL Weaton microreactor was charged with triazole 1a (~ 60 mg, 0.20
mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by deuteriated
o-tollyl acetylene (35.1 mg, 0.3 mmol). The microreactor was capped with Teflon
o
pressure cap and placed into pre-heated aluminum block at 70 C. The reaction mixture
was stirred for 12 h (as judged by TLC analysis). After completion, hexane was removed

S 8
under reduced pressure and chromatographic separation with silica gel (ethyl acetate:
1
hexane = 2:98) gave product 49 mg of 4a-d (63%) with 66% D. H NMR (500 MHz,
CDCl3): δ 7.78 (s, 1 H), 7.56 (d, J=7.34 Hz, 2 H), 7.39 (t, J=7.70 Hz, 2 H), 7.24 - 7.35
(m, 4 H), 7.06 - 7.22 (m, 4 H), 6.91 - 7.01 (m, 1 H), 2.39 (s, 3 H), 1.98 (s, 3 H).
Compound Characterization data:
Ph
Compound 4a: In a glovebox, 5 mL Weaton microreactor was charged
N
with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %) and
Ts
silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL, 0.06 M)
was added under inert atmosphere, followed by o-tollyl acetylene (34.8 mg, 0.3 mmol).
The microreactor was capped with Teflon pressure cap and placed into pre-heated
o
aluminum block at 70 C. The reaction mixture was stirred for 6 h. After completion,
hexane was removed under reduced pressure and chromatographic separation with silica
1
gel (ethyl acetate: hexane = 2:98) gave product 51.9 mg of 4a (67%); H NMR (500
MHz, CDCl3): δ 7.77 (d, J=2.02 Hz, 1 H), 7.56 (dd, J=8.25, 1.10 Hz, 2 H), 7.39 (t,
J=7.79 Hz, 2 H), 7.24 - 7.35 (m, 4 H), 7.08 - 7.21 (m, 4 H), 6.96 (dd, J=7.70, 1.28 Hz, 1
H), 6.43 (d, J=2.02 Hz, 1 H), 2.39 (s, 3 H), 1.98 (s, 3 H); 13C NMR (126 MHz, CDCl3): δ
144.8, 139.7, 135.6, 134.7, 133.5, 132.0, 130.7, 129.4, 129.4, 129.0, 128.8, 127.5, 126.9,
125.4, 124.5, 118.2, 113.7, 109.6, 21.6, 20.1. HRMS (EI) calcd. for C24H21O2NS:
387.1293. Found: 387.1300.
Ph
Compound 4b: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
N
OMe
Ts
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by 1-ethynyl-4-
methoxy-2-methylbenzene (43.9 mg, 0.3 mmol). The microreactor was capped with
o
Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The reaction
mixture was stirred for 3 h. After completion, hexane was removed under reduced
pressure and chromatographic separation with silica gel (ethyl acetate: hexane = 2:98)

S 9
gave product 80.9 mg of 4b (97%); 1H NMR (500 MHz, CDCl3): δ 7.75 (d, J=2.02 Hz, 1
H), 7.50 - 7.57 (m, 2 H), 7.38 (t, J=7.70 Hz, 2 H), 7.27 - 7.34 (m, 2 H), 7.22 - 7.26 (m, 1
H), 7.15 (d, J=8.44 Hz, 2 H), 6.87 (d, J=8.44 Hz, 1 H), 6.72 (d, J=2.57 Hz, 1 H), 6.66
(dd, J=8.34, 2.66 Hz, 1 H), 6.39 (d, J=1.83 Hz, 1 H), 3.86 (s, 3 H), 2.39 (s, 3 H), 1.92 (s,
13
3 H); C NMR (126 MHz, CDCl3): δ 160.0, 144.7, 141.2, 135.7, 134.5, 133.5, 133.2,
129.4, 128.8, 127.5, 126.9, 126.8, 125.4, 123.0, 118.1, 114.7, 113.9, 109.9, 55.2, 21.6,
20.3. HRMS (EI) calcd. for C25H23O3NS: 417.1398. Found: 417.1390.
Ph
Compound 4c: In a glovebox, 5 mL Weaton microreactor was charged
with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %)
N
Ts
and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL, 0.06
M) was added under inert atmosphere, followed by 1-ethynyl-2,4,5-trimethylbenzene
(43.3 mg, 0.3 mmol). The microreactor was capped with Teflon pressure cap and placed
into pre-heated aluminum block at 70 oC. The reaction mixture was stirred for 6 h. After
completion, hexane was removed under reduced pressure and chromatographic separation
with silica gel (ethyl acetate: hexane = 2:98) gave product 65.6 mg of 4c (79%); 1H NMR
(500 MHz, CDCl3): δ 7.75 (d, J=2.02 Hz, 1 H), 7.54 (d, J=7.89 Hz, 2 H), 7.38 (t, J=7.79
Hz, 2 H), 7.32 (d, J=8.25 Hz, 2 H), 7.23 - 7.27 (m, 1 H), 7.15 (d, J=8.44 Hz, 2 H), 6.98
(s, 1 H), 6.55 (s, 1 H), 6.38 (d, J=2.02 Hz, 1 H), 2.40 (s, 3 H), 2.29 (s, 3 H), 2.13 (s, 3 H),
13
1.96 (s, 3 H); C NMR (126 MHz, CDCl3): δ 144.4, 137.1, 136.5, 135.8, 135.6, 134.8,
133.4, 132.8, 132.0, 130.6, 129.1, 128.6, 127.8, 127.4, 126.6, 125.2, 117.8, 113.3, 21.3,
19.3, 19.2, 18.7. HRMS (EI) calcd. for C26H25O2NS: 415.1606. Found: 415.1596.
Ph
MeO
Compound 4d: In a glovebox, 5 mL Weaton microreactor was charged
with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %) and
N
Ts
silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL, 0.06 M)
was added under inert atmosphere, followed by 1-ethynyl-2-methoxybenzene (39.6 mg,
0.3 mmol). The microreactor was capped with Teflon pressure cap and placed into pre-
o
heated aluminum block at 70 C. The reaction mixture was stirred for 5 h. After
completion, hexane was removed under reduced pressure and chromatographic separation
with silica gel (ethyl acetate: hexane = 2:98) gave product 41.1 mg of 4d (51%); 1H NMR

S 10
(500 MHz, CDCl3): δ 7.73 (t, J=2.48 Hz, 1 H), 7.51 - 7.57 (m, 2 H), 7.30 - 7.42 (m, 5 H),
7.20 - 7.26 (m, 1 H), 7.14 (d, J=8.44 Hz, 2 H), 6.99 - 7.04 (m, 1 H), 6.88 - 6.94 (m, 1 H),
6.86 (dd, J=8.34, 1.93 Hz, 1 H), 6.48 (t, J=2.48 Hz, 1 H), 3.63 (s, 3 H), 2.37 (s, 3 H); 13C
NMR (126 MHz, CDCl3): δ 158.4, 144.1, 135.7, 133.3, 132.6, 132.1, 130.2, 129.1, 128.4,
127.1, 127.0, 126.5, 125.2, 120.2, 119.2, 118.4, 113.8, 110.1, 54.9, 21.3. HRMS (EI)
calcd. for C24H21O3NS: 403.1242. Found: 403.1256.
Ph
Compound 4e: In a glovebox, 5 mL Weaton microreactor was charged
with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %) and
N
Ts
silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL, 0.06 M)
was added under inert atmosphere, followed by 1-ethynylcyclohex-1-ene (31.8 mg, 0.3
mmol). The microreactor was capped with Teflon pressure cap and placed into pre-heated
o
aluminum block at 70 C. The reaction mixture was stirred for 5 h. After completion,
hexane was removed under reduced pressure and chromatographic separation with silica
1
gel (ethyl acetate: hexane = 2:98) gave product 39.2 mg of 4e (52%); H NMR (400
MHz, CDCl3): δ 7.63 (d, J=8.18 Hz, 2 H), 7.57 (d, J=1.90 Hz, 1 H), 7.49 (d, J=8.04 Hz, 2
H), 7.35 (t, J=7.67 Hz, 2 H), 7.19 - 7.30 (m, 3 H), 6.29 (d, J=1.75 Hz, 1 H), 5.46 (br. s., 1
H), 2.39 (s, 3 H), 2.21 (d, J=1.90 Hz, 2 H), 2.09 (dd, J=5.63, 2.70 Hz, 2 H), 1.60 - 1.79
(m, 4 H); 13C NMR (101 MHz, CDCl3): δ 144.3, 139.1, 135.6, 133.1, 130.8, 129.7, 129.1,
128.4, 127.1, 126.8, 126.5, 125.0, 118.2, 111.6, 30.3, 25.3, 22.4, 21.3, 21.3. HRMS (EI)
calcd. for C23H23O2NS: 377.1449. Found: 377.1440.
Ph
Compound 4f: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
N
OPh
Ts
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by 1-ethynyl-4-
phenoxybenzene (58.3 mg, 0.3 mmol). The microreactor was capped with Teflon
o
pressure cap and placed into pre-heated aluminum block at 70 C. The reaction mixture
was stirred for 5 h. After completion, hexane was removed under reduced pressure and
chromatographic separation with silica gel (ethyl acetate: hexane = 3:98) gave product
48.4 mg of 4f (52%); 1H NMR (500 MHz, CDCl3): δ 7.73 (d, J=2.02 Hz, 1 H), 7.54 (dd,

S 11
J=8.34, 1.19 Hz, 2 H), 7.34 - 7.42 (m, 4 H), 7.30 - 7.33 (m, 2 H), 7.26 - 7.29 (m, 1 H),
7.21 - 7.26 (m, 2 H), 7.16 (t, J=7.34 Hz, 1 H), 7.13 (d, J=8.07 Hz, 2 H), 7.06 - 7.11 (m, 2
H), 6.95 - 6.97 (m, 1 H), 6.93 - 6.95 (m, 1 H), 6.48 (d, J=2.02 Hz, 1 H), 2.36 (s, 3 H); 13C
NMR (126 MHz, CDCl3): δ 157.7, 156.7, 144.8, 136.2, 135.5, 133.3, 132.3, 129.8, 129.4,
128.8, 127.4, 127.2, 127.1, 125.9, 125.4, 123.6, 119.4, 119.2, 117.4, 114.2, 21.6. HRMS
(EI) calcd. for C29H23O3NS: 465.1398. Found: 465.1401.
Ph
Compound 4g: In a glovebox, 5 mL Weaton microreactor was charged
with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %) and
N
Ts
silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL, 0.06 M)
was added under inert atmosphere, followed by 1-ethynyl-2-isopropylbenzene (43.3 mg,
0.3 mmol). The microreactor was capped with Teflon pressure cap and placed into pre-
o
heated aluminum block at 70 C. The reaction mixture was stirred for 12 h. After
completion, hexane was removed under reduced pressure and chromatographic separation
with silica gel (ethyl acetate: hexane = 2:98) gave product 44.8 mg of 4g (54%); 1H NMR
(500 MHz, CDCl3): δ 7.78 (d, J=2.02 Hz, 1 H), 7.51 - 7.60 (m, 2 H), 7.32 - 7.43 (m, 6 H),
7.24 - 7.31 (m, 1 H), 7.17 (d, J=8.07 Hz, 2 H), 6.99 - 7.07 (m, 1 H), 6.73 (dd, J=7.61,
1.19 Hz, 1 H), 6.46 (d, J=2.02 Hz, 1 H), 2.79 - 2.93 (m, 1 H), 2.39 (s, 3 H), 1.19 (d,
J=6.79 Hz, 3 H), 1.06 (d, J=6.79 Hz, 3 H); 13C NMR (126 MHz, CDCl3): δ 150.6, 145.0,
136.2, 134.6, 133.8, 132.1, 129.8, 129.7, 129.6, 129.1, 127.8, 127.2, 127.0, 125.7, 125.2,
124.5, 118.3, 114.3, 30.8, 26.0, 22.1, 21.8. HRMS (EI) calcd. for C26H25O2NS: 415.1606.
Found: 415.1608.
Ph
Compound 4h: In a glovebox, 5 mL Weaton microreactor was charged
with triazole 1a (~ 60 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %)
N
Ts
and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL, 0.06
M) was added under inert atmosphere, followed by 1-ethynyl-2,3-dimethylbenzene (39.1
mg, 0.3 mmol). The microreactor was capped with Teflon pressure cap and placed into
o
pre-heated aluminum block at 70 C. The reaction mixture was stirred for 12 h. After
completion, hexane was removed under reduced pressure and chromatographic separation
with silica gel (ethyl acetate: hexane = 2:98) gave product 53.0 mg of 4h (66%); 1H NMR

S 12
(500 MHz, CDCl3): δ 7.77 (d, J=2.02 Hz, 1 H), 7.53 - 7.59 (m, 2 H), 7.35 - 7.43 (m, 2 H),
7.24 - 7.32 (m, 3 H), 7.21 (d, J=7.52 Hz, 1 H), 7.14 (d, J=7.89 Hz, 2 H), 7.03 (t, J=7.61
Hz, 1 H), 6.82 (d, J=7.34 Hz, 1 H), 6.42 (d, J=2.02 Hz, 1 H), 2.39 (s, 3 H), 2.27 (s, 3 H),
13
1.82 (s, 3 H); C NMR (126 MHz, CDCl3): δ 144.5, 138.2, 136.1, 135.4, 135.0, 133.3,
130.5, 130.2, 129.6, 129.1, 128.5, 127.4, 126.6, 126.4, 125.1, 123.9, 117.6, 113.2, 21.3,
20.1, 16.7. HRMS (EI) calcd. for C25H23O2NS: 401.1449. Found: 401.1456.
EtO2C
Compound 4i: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1b (~ 74.3 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
Ts
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
followed by 1-ethynyl-2,4,5-trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor
was capped with Teflon pressure cap and placed into pre-heated aluminum block at 70
oC. The reaction mixture was stirred for 12 h. After completion, hexane was removed
under reduced pressure and chromatographic separation with silica gel (ethyl acetate:
1
hexane = 4:96) gave product 72.1 mg of 4i (74%); H NMR (500 MHz, CDCl3): δ 8.05
(d, J=8.07 Hz, 2 H), 7.84 (s, 1 H), 7.60 (d, J=8.07 Hz, 2 H), 7.31 (d, J=8.25 Hz, 2 H),
7.16 (d, J=8.07 Hz, 2 H), 6.98 (s, 1 H), 6.53 (s, 1 H), 6.41 (s, 1 H), 4.39 (q, J=7.03 Hz, 2
H), 2.40 (s, 3 H), 2.29 (s, 3 H), 2.13 (s, 3 H), 1.95 (s, 3 H), 1.41 (t, J=7.15 Hz, 3 H); 13C
NMR (126 MHz, CDCl3): δ 166.6, 145.2, 138.3, 137.7, 137.1, 135.8, 135.5, 133.3, 132.6,
131.1, 130.4, 129.6, 128.9, 128.0, 125.9, 125.3, 119.2, 113.4, 61.1, 21.8, 19.8, 19.7, 19.2,
14.6. HRMS (EI) calcd. for C29H29O4NS: 487.1817. Found: 487.1808.
EtO2C
Compound 4j: In a glovebox, 5 mL Weaton microreactor
was charged with triazole 1b (~ 74.3 mg, 0.20 mmol),
Rh2(oct)4 (3.9 mg, 2.5 mol %) and silver trifluoroacetate (2.2
N
OMe
Ts
mg, 5.0 mol %). Dry hexane (3 mL, 0.06M) was added under
inert atmosphere, followed by 1-ethynyl-4-methoxy-2-methylbenzene (43.9 mg, 0.3
mmol). The microreactor was capped with Teflon pressure cap and placed into pre-heated
o
aluminum block at 70 C. The reaction mixture was stirred for 4 h. After completion,
hexane was removed under reduced pressure and chromatographic separation with silica

S 13
gel (ethyl acetate: hexane = 4:96) gave product 92.0 mg of 4j (94%); 1H NMR (500 MHz,
CDCl3): δ 8.05 (d, J=8.80 Hz, 2 H), 7.85 (d, J=1.83 Hz, 1 H), 7.53 - 7.64 (m, 2 H), 7.32
(d, J=8.44 Hz, 2 H), 7.16 (d, J=8.44 Hz, 2 H), 6.86 (d, J=8.07 Hz, 1 H), 6.60 - 6.75 (m, 2
H), 6.42 (d, J=2.20 Hz, 1 H), 4.39 (q, J=7.09 Hz, 2 H), 3.85 (s, 3 H), 2.39 (s, 3 H), 1.90
13
(s, 3 H), 1.41 (t, J=7.15 Hz, 3 H); C NMR (126 MHz, CDCl3): δ 166.1, 159.8, 144.7,
140.9, 137.8, 135.2, 134.6, 133.0, 129.8, 129.2, 128.4, 127.3, 125.4, 124.8, 122.4, 118.8,
114.5, 113.3, 109.8, 60.6, 54.9, 21.3, 20.1, 14.1. HRMS (EI) calcd. for C28H27O5NS:
489.1609. Found: 489.1620.
EtO2C
Compound 4k: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1b (~ 74.3 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
Ts
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
followed by 1-ethynyl-2,3-dimethylbenzene (39.1 mg, 0.3 mmol). The microreactor was
o
capped with Teflon pressure cap and placed into pre-heated aluminum block at 70 C.
The reaction mixture was stirred for 9 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
4:96) gave product 54.9 mg of 4k (58%); 1H NMR (500 MHz, CDCl3): δ 8.05 (d, J=8.44
Hz, 2 H), 7.85 (d, J=2.20 Hz, 1 H), 7.60 (d, J=8.44 Hz, 2 H), 7.26 - 7.30 (m, 2 H), 7.21
(d, J=7.70 Hz, 1 H), 7.14 (d, J=8.07 Hz, 2 H), 7.02 (t, J=7.70 Hz, 1 H), 6.81 (d, J=7.34
Hz, 1 H), 6.44 (d, J=2.20 Hz, 1 H), 4.39 (q, J=7.21 Hz, 2 H), 2.40 (s, 3 H), 2.25 (s, 3 H),
13
1.79 (s, 3 H), 1.41 (t, J=7.15 Hz, 3 H); C NMR (126 MHz, CDCl3): δ 166.2, 144.6,
138.2, 137.8, 135.3, 135.1, 130.4, 130.2, 129.8, 129.6, 129.1, 128.4, 127.5, 125.3, 124.8,
124.0, 118.5, 112.9, 60.6, 21.3, 20.1, 16.7, 14.1. HRMS (EI) calcd. for C28H27O4NS:
473.1660. Found: 473.1671.
EtO2C
Compound 4l: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1b (~ 74.3 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
Ts
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
followed by 2-ethynyl-1,3,5-trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor

S 14
was capped with Teflon pressure cap and placed into pre-heated aluminum block at 70
oC. The reaction mixture was stirred for 9 h. After completion, hexane was removed
under reduced pressure and chromatographic separation with silica gel (ethyl acetate:
1
hexane = 4:96) gave product 70.2 mg of 4l (72%); H NMR (500 MHz, CDCl3): δ 8.06
(d, J=8.44 Hz, 2 H), 7.91 (d, J=1.83 Hz, 1 H), 7.58 - 7.65 (m, 2 H), 7.34 (d, J=8.44 Hz, 2
H), 7.17 (d, J=8.07 Hz, 2 H), 6.84 (s, 2 H), 6.39 (d, J=2.20 Hz, 1 H), 4.39 (q, J=6.97 Hz,
2 H), 2.41 (s, 3 H), 2.35 (s, 3 H), 1.71 (s, 6 H), 1.42 (t, J=7.15 Hz, 3 H); 13C NMR (126
MHz, CDCl3): δ 166.2, 144.8, 139.6, 138.5, 137.9, 134.8, 133.4, 129.8, 129.2, 128.3,
127.9, 127.3, 126.9, 125.2, 124.8, 118.5, 112.5, 60.6, 21.3, 20.9, 19.9, 14.1. HRMS (EI)
calcd. for C29H29O4NS: 487.1817. Found: 487.1826.
EtO2C
Compound 4m: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1b (~ 74.3 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
Ts
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
followed by 1-ethynyl-2-isopropylbenzene (43.3 mg, 0.3 mmol). The microreactor was
o
capped with Teflon pressure cap and placed into pre-heated aluminum block at 70 C.
The reaction mixture was stirred for 8 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
4:96) gave product 44.8 mg of 4m (46%); 1H NMR (500 MHz, CDCl3): δ 8.06 (d, J=8.44
Hz, 2 H), 7.86 (s, 1 H), 7.61 (d, J=8.44 Hz, 2 H), 7.30 - 7.43 (m, 4 H), 7.17 (d, J=8.07
Hz, 2 H), 7.02 (t, J=7.34 Hz, 1 H), 6.70 (d, J=7.70 Hz, 1 H), 6.48 (s, 1 H), 4.39 (q, J=7.34
Hz, 2 H), 2.77 - 2.88 (m, 1 H), 2.39 (s, 3 H), 1.41 (t, J=6.97 Hz, 3 H), 1.17 (d, J=6.60 Hz,
13
3 H), 1.05 (d, J=6.97 Hz, 3 H); C NMR (126 MHz, CDCl3): δ 166.1, 144.7, 137.7,
135.4, 134.4, 131.5, 129.9, 129.3, 129.0, 128.5, 127.4, 125.4, 124.8, 124.7, 124.0, 121.9,
118.8, 113.5, 60.6, 30.4, 25.6, 21.6, 21.3, 14.1. HRMS (EI) calcd. for C29H29O4NS:
487.1817. Found: 487.1829.
EtO2C
Compound 4n: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1b (~ 74.3 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
Ts

S 15
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by o-tollyl
acetylene (34.8 mg, 0.3 mmol). The microreactor was capped with Teflon pressure cap
and placed into pre-heated aluminum block at 70 oC. The reaction mixture was stirred for
8 h. After completion, hexane was removed under reduced pressure and chromatographic
separation with silica gel (ethyl acetate: hexane = 4:96) gave product 59.7 mg of 4n
1
(65%); H NMR (500 MHz, CDCl3): δ 8.01 - 8.10 (m, 2 H), 7.85 (d, J=1.83 Hz, 1 H),
7.60 (d, J=8.44 Hz, 2 H), 7.27 - 7.36 (m, 3 H), 7.06 - 7.21 (m, 4 H), 6.94 (dd, J=7.70,
1.47 Hz, 1 H), 6.46 (d, J=1.83 Hz, 1 H), 4.39 (q, J=6.97 Hz, 2 H), 2.39 (s, 3 H), 1.95 (s, 3
H), 1.41 (t, J=7.15 Hz, 3 H); 13C NMR (126 MHz, CDCl3): δ 166.6, 145.2, 139.9, 138.2,
135.6, 135.2, 132.3, 130.7, 130.4, 129.7, 129.6, 129.3, 128.9, 127.8, 126.3, 126.0, 125.3,
124.8, 119.3, 113.6, 61.1, 21.8, 20.2, 14.6. HRMS (EI) calcd. for C27H25O4NS: 459.1504.
Found: 459.1515.
EtO2C
Compound 4o: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1b (~ 74.3 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
Ts
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
followed by 4-ethynyl-1,2-dimethylbenzene (39.1 mg, 0.3 mmol). The microreactor was
o
capped with Teflon pressure cap and placed into pre-heated aluminum block at 70 C.
The reaction mixture was stirred for 9 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
4:96) gave product 56.8 mg of 4o (60%); 1H NMR (500 MHz, CDCl3): δ 8.05 (d, J=8.44
Hz, 2 H), 7.85 (d, J=2.20 Hz, 1 H), 7.60 (d, J=8.44 Hz, 2 H), 7.28 (d, J=8.44 Hz, 2 H),
7.21 (d, J=7.70 Hz, 1 H), 7.14 (d, J=8.07 Hz, 2 H), 7.02 (t, J=7.70 Hz, 1 H), 6.81 (d,
J=7.34 Hz, 1 H), 6.44 (d, J=2.20 Hz, 1 H), 4.39 (q, J=7.21 Hz, 2 H), 2.40 (s, 3 H), 2.25
13
(s, 3 H), 1.79 (s, 3 H), 1.41 (t, J=7.15 Hz, 3 H); C NMR (126 MHz, CDCl3): δ 166.6,
145.1, 138.2, 137.5, 135.8, 133.2, 132.2, 130.3, 129.6, 129.0, 128.6, 127.6, 126.4, 125.3,
121.6, 120.2, 113.7, 111.8, 109.1, 61.1, 21.8, 19.8, 19.8, 14.6. HRMS (EI) calcd. for
C28H27O4NS: 473.1660. Found: 473.1653.

S 16
Compound 4p: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1c (~ 62.7 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
N
OMe
Ts
followed by 1-ethynyl-4-methoxy-2-methylbenzene (43.9 mg, 0.3 mmol). The
microreactor was capped with Teflon pressure cap and placed into pre-heated aluminum
o
block at 70 C. The reaction mixture was stirred for 12 h. After completion, hexane was
removed under reduced pressure and chromatographic separation with silica gel (ethyl
acetate: hexane = 2:98) gave product 69.8 mg of 4p (81%); 1H NMR (500 MHz, CDCl3):
δ 7.72 (d, J=1.83 Hz, 1 H), 7.44 (d, J=8.07 Hz, 2 H), 7.32 (d, J=8.44 Hz, 2 H), 7.20-7.16
(m, 4 H), 6.87 (d, J=8.44 Hz, 1 H), 6.73 (d, J=2.57 Hz, 1 H), 6.66 (dd, J=8.44, 2.57 Hz, 1
H), 6.37 (d, J=2.20 Hz, 1 H), 3.86 (s, 3 H), 2.39 (s, 3 H), 2.37 (s, 3 H), 1.93 (s, 3 H); 13C
NMR (126 MHz, CDCl3): δ 160.2, 144.9, 141.5, 136.9, 136.0, 134.7, 133.5, 130.9, 129.7,
129.6, 127.7, 127.1, 125.5, 123.4, 118.0, 114.9, 114.2, 110.2, 55.4, 21.8, 21.4, 20.6.
HRMS (EI) calcd. for C26H25O3NS: 431.1555. Found: 431.1563.
Compound 4q: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1c (~ 62.7 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
N
Ts
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed
by 1-ethynyl-2,4,5-trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor was capped
o
with Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The
reaction mixture was stirred for 12 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
2:98) gave product 66.1 mg of 4q (77%); 1H NMR (500 MHz, CDCl3): δ 7.71 (d, J=2.20
Hz, 1 H), 7.44 (d, J=8.07 Hz, 2 H), 7.32 (d, J=8.44 Hz, 2 H), 7.19 (d, J=7.70 Hz, 2 H),
7.15 (d, J=8.07 Hz, 2 H), 6.98 (s, 1 H), 6.56 (s, 1 H), 6.36 (d, J=1.83 Hz, 1 H), 2.40 (s, 3
13
H), 2.37 (s, 3 H), 2.29 (s, 3 H), 2.14 (s, 3 H), 1.97 (s, 3 H); C NMR (126 MHz, C): δ
144.6, 137.3, 136.8, 136.6, 135.8, 134.9, 133.1, 132.3, 130.8, 130.7, 129.5, 129.3, 128.1,
127.6, 126.9, 125.3, 117.7, 113.5, 21.6, 21.1, 19.5, 19.4, 18.9. HRMS (EI) calcd. for
C27H27O2NS: 429.1762. Found: 429.1771.

S 17
Compound 4r: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1c (~ 62.7 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed
N
Ts
by 2-ethynyl-1,3,5-trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor was capped
o
with Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The
reaction mixture was stirred for 7 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
2:98) gave product 74.7 mg of 4r (87%); 1H NMR (500 MHz, CDCl3): δ 7.79 (d, J=2.20
Hz, 1 H), 7.47 (d, J=8.07 Hz, 2 H), 7.35 (d, J=8.07 Hz, 2 H), 7.21-7.18 (m, 4 H), 6.84 (s,
2 H), 6.35 (d, J=1.83 Hz, 1 H), 2.41 (s, 3 H), 2.38 (s, 3 H), 2.35 (s, 3 H), 1.73 (s, 6 H);
13C NMR (126 MHz, CDCl3): δ 144.5, 139.5, 138.3, 136.2, 135.2, 132.8, 130.5, 129.2,
129.1, 127.7, 127.3, 127.3, 126.2, 125.0, 117.1, 112.8, 21.3, 21.0, 20.9, 20.0. HRMS (EI)
calcd. for C27H27O2NS: 429.1762. Found: 429.1751.
Compound 4s: In a glovebox, 5 mL Weaton microreactor was charged
with triazole 1c (~ 62.7 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg, 2.5 mol %)
and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry hexane (3 mL,
N
Ts
0.06 M) was added under inert atmosphere, followed by o-tollyl
acetylene (34.8 mg, 0.3 mmol). The microreactor was capped with Teflon pressure cap
and placed into pre-heated aluminum block at 70 oC. The reaction mixture was stirred for
7 h. After completion, hexane was removed under reduced pressure and chromatographic
separation with silica gel (ethyl acetate: hexane = 2:98) gave product 43.3 mg of 4s
1
(54%); H NMR (500 MHz, CDCl3): δ 7.72 (d, J=1.83 Hz, 1 H), 7.44 (d, J=8.44 Hz, 2
H), 7.30 (d, J=8.44 Hz, 2 H), 7.16 - 7.22 (m, 4 H), 7.08 - 7.16 (m, 3 H), 6.93 - 6.99 (m, 1
13
H), 6.40 (d, J=1.83 Hz, 1 H), 2.39 (s, 3 H), 2.37 (s, 3 H), 1.97 (s, 3 H); C NMR (126
MHz, CDCl3): δ 144.7, 142.4, 139.6, 136.7, 134.6, 133.9, 132.0, 130.6, 129.4, 129.4,
128.9, 127.4, 126.9, 125.3, 124.5, 117.8, 115.6, 113.8, 21.5, 21.1, 20.1. HRMS (EI)
calcd. for C25H23O2NS: 401.1449. Found: 401.1457.

S 18
Compound 4t: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1c (~ 62.7 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed
N
Ts
by 1-ethynyl-2,3-dimethylbenzene (39.1 mg, 0.3 mmol). The microreactor was capped
o
with Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The
reaction mixture was stirred for 10 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
2:98) gave product 58.1 mg of 4t (70%); 1H NMR (500 MHz, CDCl3): δ 7.73 (d, J=1.83
Hz, 1 H), 7.45 (d, J=8.07 Hz, 2 H), 7.29 (d, J=8.44 Hz, 2 H), 7.17 - 7.22 (m, 3 H), 7.13
(d, J=7.70 Hz, 2 H), 7.03 (t, J=7.70 Hz, 1 H), 6.82 (d, J=7.34 Hz, 1 H), 6.40 (d, J=2.20
13
Hz, 1 H), 2.39 (s, 3 H), 2.37 (s, 3 H), 2.27 (s, 3 H), 1.82 (s, 3 H); C NMR (126 MHz,
CDCl3): δ 144.8, 138.6, 136.8, 136.5, 135.4, 131.1, 130.9, 130.6, 130.1, 129.7, 129.5,
127.8, 127.0, 125.5, 124.4, 117.7, 113.8, 21.8, 21.3, 20.6, 17.2. HRMS (EI) calcd. for
C26H25O2NS: 415.1606. Found: 415.1621.
Br
Compound 4u: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1d (~ 75.6 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
N
OMe
Ts
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere,
followed by 1-ethynyl-4-methoxy-2-methylbenzene (43.9 mg, 0.3 mmol). The
microreactor was capped with Teflon pressure cap and placed into pre-heated aluminum
o
block at 70 C. The reaction mixture was stirred for 10 h. After completion, hexane was
removed under reduced pressure and chromatographic separation with silica gel (ethyl
acetate: hexane = 3:97) gave product 98.0 mg of 4u (99%); 1H NMR (500 MHz, CDCl3):
δ 7.75 (d, J=2.20 Hz, 1 H), 7.46 - 7.52 (m, 2 H), 7.38 - 7.43 (m, 2 H), 7.31 (d, J=8.44 Hz,
2 H), 7.16 (d, J=8.07 Hz, 2 H), 6.86 (d, J=8.44 Hz, 1 H), 6.72 (d, J=2.93 Hz, 1 H), 6.66
(dd, J=8.44, 2.57 Hz, 1 H), 6.34 (d, J=1.83 Hz, 1 H), 3.86 (s, 3 H), 2.39 (s, 3 H), 1.91 (s,
13
3 H); C NMR (126 MHz, CDCl3): δ 160.3, 145.1, 141.4, 135.7, 134.9, 133.5, 132.8,
132.1, 129.7, 127.8, 127.2, 125.8, 123.0, 120.7, 118.4, 114.9, 113.7, 110.2, 55.4, 21.8,
20.5. HRMS (EI) calcd. for C25H22O3NBrS: 495.0503. Found: 495.0488.

S 19
Br
Compound 4v: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1d (~ 75.6 mg, 0.20 mmol), Rh2(oct)4 (3.9
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed
N
Ts
by 1-ethynyl-2,4,5-trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor was capped
o
with Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The
reaction mixture was stirred for 12 h. After completion, hexane was removed under
reduced pressure and chromatographic separation with silica gel (ethyl acetate: hexane =
3:97) gave product 84.8 mg of 4v (86%); 1H NMR (500 MHz, CDCl3): δ 7.74 (d, J=1.83
Hz, 1 H), 7.45 - 7.53 (m, 2 H), 7.40 (d, J=8.25 Hz, 2 H), 7.31 (d, J=8.25 Hz, 2 H), 7.16
(d, J=8.25 Hz, 2 H), 6.98 (s, 1 H), 6.54 (s, 1 H), 6.33 (d, J=1.83 Hz, 1 H), 2.40 (s, 3 H),
13
2.29 (s, 3 H), 2.13 (s, 3 H), 1.95 (s, 3 H); C NMR (126 MHz, CDCl3): δ 145.1, 137.7,
137.0, 135.8, 135.4, 133.3, 132.8, 132.6, 132.1, 131.1, 129.6, 128.0, 127.9, 127.2, 125.9,
120.7, 118.3, 113.3, 21.8, 19.8, 19.7, 19.2. HRMS (EI) calcd. for C26H24O2NBrS:
493.0722. Found: 493.0711.
Compound 4w: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1e (~ 55.9 mg, 0.20 mmol), Rh2(oct)4 (3.9
N
OMe
Ts
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by 1-ethynyl-4-
methoxy-2-methylbenzene (43.9 mg, 0.3 mmol). The microreactor was capped with
o
Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The reaction
mixture was stirred for 12 h. After completion, hexane was removed under reduced
pressure and chromatographic separation with silica gel (ethyl acetate: hexane = 2:98)
gave product 35.0 mg of 4w (44%); 1H NMR (500 MHz, CDCl3): δ 7.23 - 7.31 (m, 2 H),
7.10 - 7.19 (m, 3 H), 6.82 (d, J=8.25 Hz, 1 H), 6.69 (d, J=2.57 Hz, 1 H), 6.63 (dd, J=8.25,
2.75 Hz, 1 H), 5.91 (d, J=1.83 Hz, 1 H), 3.83 (s, 3 H), 2.42 (t, J=7.34 Hz, 2 H), 2.38 (s, 3
H), 1.89 (s, 3 H), 1.55 (t, J=7.70 Hz, 2 H), 1.29 - 1.41 (m, 2 H), 0.93 (t, J=7.43 Hz, 3 H);
13C NMR (126 MHz, CDCl3): δ 159.5, 144.0, 140.7, 133.4, 132.8, 128.9, 128.4, 127.2,

S 20
127.0, 121.4, 118.9, 116.6, 114.4, 109.6, 54.9, 31.8, 26.2, 22.0, 21.3, 20.1, 13.6. HRMS
(EI) calcd. for C23H27O3NS: 397.1699. Found: 397.1711.
EtO2C
Compound 4x: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1f (~ 59.0 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
N
Ts
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by 1-ethynyl-2,4,5-
trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor was capped with Teflon
o
pressure cap and placed into pre-heated aluminum block at 70 C. The reaction mixture
was stirred for 15 h. After completion, hexane was removed under reduced pressure and
chromatographic separation with silica gel (ethyl acetate: hexane = 5:95) gave product
1
46.9 mg of 4x (57%); H NMR (500 MHz, CDCl3): δ 8.09 (d, J=1.83 Hz, 1 H), 7.22 -
7.29 (m, 2 H), 7.15 (d, J=7.89 Hz, 2 H), 6.94 (s, 1 H), 6.45 (s, 1 H), 6.42 (d, J=2.02 Hz, 1
H), 4.31 (q, J=7.15 Hz, 2 H), 2.41 (s, 3 H), 2.27 (s, 3 H), 2.09 (s, 3 H), 1.85 (s, 3 H), 1.36
13
(t, J=7.15 Hz, 3 H); C NMR (126 MHz, CDCl3): δ 164.0, 145.5, 137.9, 137.1, 135.2,
134.5, 133.4, 132.6, 131.0, 129.8, 128.3, 127.3, 126.8, 118.5, 114.5, 60.6, 21.8, 19.8,
19.5, 19.2, 14.6. HRMS (EI) calcd. for C23H25O4NS: 411.1513. Found: 411.1504.
EtO2C
Compound 4y: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1f (~ 59.0 mg, 0.20 mmol), Rh2(oct)4 (3.9 mg,
N
Ts
2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %). Dry
hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by 2-ethynyl-1,3,5-
trimethylbenzene (43.3 mg, 0.3 mmol). The microreactor was capped with Teflon
o
pressure cap and placed into pre-heated aluminum block at 70 C. The reaction mixture
was stirred for 15 h. After completion, hexane was removed under reduced pressure and
chromatographic separation with silica gel (ethyl acetate: hexane = 5:95) gave product
1
37.8 mg of 4y (46%); H NMR (500 MHz, CDCl3): δ 8.14 (d, J=1.83 Hz, 1 H), 7.24 -
7.32 (m, 2 H), 7.16 (d, J=8.07 Hz, 2 H), 6.80 (s, 2 H), 6.40 (d, J=1.83 Hz, 1 H), 4.32 (q,
J=7.15 Hz, 2 H), 2.41 (s, 3 H), 2.33 (s, 3 H), 1.63 (s, 6 H), 1.37 (t, J=7.15 Hz, 3 H); 13C
NMR (126 MHz, CDCl3): δ 163.6, 145.2, 139.7, 138.7, 134.1, 132.7, 129.2, 128.2, 127.3,

S 21
126.3, 126.3, 117.9, 113.9, 60.1, 21.4, 20.9, 19.8, 14.1. HRMS (EI) calcd. for
C23H25O4NS: 411.1487. Found: 411.1504.
Compound 4z: In a glovebox, 5 mL Weaton microreactor was
charged with triazole 1g (~ 44.6 mg, 0.20 mmol), Rh2(oct)4 (3.9
N
OMe
Ts
mg, 2.5 mol %) and silver trifluoroacetate (2.2 mg, 5.0 mol %).
Dry hexane (3 mL, 0.06 M) was added under inert atmosphere, followed by 1-ethynyl-4-
methoxy-2-methylbenzene (43.9 mg, 0.3 mmol). The microreactor was capped with
o
Teflon pressure cap and placed into pre-heated aluminum block at 70 C. The reaction
mixture was stirred for 20 h. After completion, hexane was removed under reduced
pressure and chromatographic separation with silica gel (ethyl acetate: hexane = 1:99)
gave product 36.8 mg of 4z (54%); 1H NMR (500 MHz, CDCl3): δ 7.45 (dd, J=3.30, 1.83
Hz, 1 H), 7.25 - 7.30 (m, 2 H), 7.15 (d, J=8.07 Hz, 2 H), 6.82 (d, J=8.44 Hz, 1 H), 6.70
(d, J=2.57 Hz, 1 H), 6.63 (dd, J=8.44, 2.93 Hz, 1 H), 6.31 (t, J=3.30 Hz, 1 H), 6.05 (dd,
13
J=3.30, 1.83 Hz, 1 H), 3.84 (s, 3 H), 2.38 (s, 3 H), 1.85 (s, 3 H); C NMR (126 MHz,
CDCl3): 159.8, 144.5, 135.8, 133.5, 133.3, 129.3, 127.4, 123.2, 122.5, 115.3, 114.6,
111.2, 110.5, 109.8, 55.1, 21.5, 20.2. HRMS (EI) calcd. for C19H19O3NS: 341.1074.
Found: 341.1085.

S 22
References:
[1] Yoo, E. J; Ahlquist, M.; Kim, S. H.; Bae, I.; Fokin, V.V.; Sharpless, K. B.; Chang, S.
Angew. Chem. Int. Ed. 2007, 46, 1730.
[2] Keith, J. M. J. Org. Chem. 2010, 75, 2722.
[3] Ishihara, K.; Nakano, K.; Ishibashi, H.; Yamamoto, H. Chirality 2003, 15, 135.
[4] Nepveu, F.; Kim, S.; Boyer, J.; Chatriant, O.; Ibrahim, H.; Reybier, K.; Monje, M.-C.;
Chevalley, S.; Perio, P.; Lajoie, B. H.; Bouajila, J.; Deharo, E.; Sauvain, M.; Tahar, R.;
Basco, L.; Pantaleo, A.; Turini, F.; Arese, P.; Valentin, A.; Thompson, E.; Vivas, L.;
Petit, S.; Nallet, J.-P. J. Med. Chem. 2010, 53, 699.

S 23
Copies of NMR spectra:
1H Spectrum of 1e (500 MHz, CDCl3)
N
N
N
Ts
1.70
8
1.87
2.99
2.39 3.00
1
9
7
6
5
4
3
2
0
Chemical Shift (ppm)
13C Spectrum of 1e (126 MHz, CDCl3)
N
N
N
Ts
160
140
120
100
80
60
40
20
0
Chemical Shift (ppm)

S 24
1H Spectrum of 4a (500 MHz, CDCl3)
O S O
N
9
8
7
6
5
4
3
2
1
0
Chemical Shift (ppm)
13C Spectrum of 4a (126 MHz, CDCl3)
O S O
N
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
Chemical Shift (ppm)

S 25
1H Spectrum of 4b (500 MHz, CDCl3)
O
S
N
O
O
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)
13C Spectrum of 4b (126 MHz, CDCl3)
O
S
N
O
O
176
168
160
152
144
136
128
120
112
104
96
88
80
72
64
56
48
40
32
24
16
8
0
Chemical Shift (ppm)

S 26
1H Spectrum of 4c (500 MHz, CDCl3)
O
S
N
O
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)
13C Spectrum of 4c (126 MHz, CDCl3)
O S
N
O
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
Chemical Shift (ppm)

S 27
1H Spectrum of 4d (500 MHz, CDCl3)
O
S
N
O
O
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)
13C Spectrum of 4d (126 MHz, CDCl3)
O
S O
N
O
176
168
160
152
144
136
128
120
112
104
96
88
80
72
64
56
48
40
32
24
16
8
0
Chemical Shift (ppm)

S 28
1H Spectrum of 4e (400 MHz, CDCl3)
O
S
N
O
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)
13C Spectrum of 4e (101 MHz, CDCl3)
O
S
N
O
176
168
160
152
144
136
128
120
112
104
96
88
80
72
64
56
48
40
32
24
16
8
0
Chemical Shift (ppm)

S 29
1H Spectrum of 4f (500 MHz, CDCl3)
O
S
N
O
O
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)
13C Spectrum of 4f (126 MHz, CDCl3)
O
S
N
O
O
176
168
160
152
144
136
128
120
112
104
96
88
80
72
64
56
48
40
32
24
16
8
0
Chemical Shift (ppm)

S 30
1H Spectrum of 4g (500 MHz, CDCl3)
O
S
N
O
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
Chemical Shift (ppm)
13C Spectrum of 4g (126 MHz, CDCl3)
O S
N
O
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
Chemical Shift (ppm)