Sulfonylation of Imidazo[1,2-a]pyridines Supporting

S1

Supporting information

An Electrolyte- and Catalyst-Free Electrooxidative

Sulfonylation of Imidazo[1,2-a]pyridines

Lili Han,‡ Mengmeng Huang,‡ Yabo Li, Jianye Zhang, Yu Zhu, Jung Keun Kim* and Yangjie Wu*

College of Chemistry, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052,

China

*E-mail: [email protected], [email protected]

Table of Contents

1. General Information...................................................................................................2

2. Experimental Procedure.............................................................................................2

3. Cyclic Voltammetry Experiments ...............................................................................3

4. Control Experiments...................................................................................................4

5. Optical spectroscopy data..........................................................................................6

6. Computational Details................................................................................................8

7. Characterization Data...............................................................................................17

8. 1H, 13C and 19F NMR Spectra.....................................................................................28

9. X-Ray Crystallographic Data .....................................................................................60

Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers.This journal is © the Partner Organisations 2021

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1. General Information

Solvents were dried and degassed by standard methods before they were used. Commercial grade reagents were used without further purification except as indicated below. Imidazo[1,2-a]pyridines were synthesized according to the method in the literature.1 Sodium sulfinates (2a-2b, 2e, 2f, 2k) were purchased from commercial suppliers and (2c-2d, 2g-2j) were prepared according to the method in the literature.2 Electrolysis was conducted using a DC power supply (MWSTEK DP3005B) in constant current mode. The anode electrode is graphite rod (Φ = 6 mm) and cathode electrode is Nickel plate electrode (10 mm × 10 mm × 0.2 mm). Analytical thin-layer chromatography (TLC) was performed on Merck silica gel aluminum plates with F-254 indicator, visualized by irradiation with UV light. The LCD Digital Hotplate Magnetic Stirrer MS-H-Pro+ and Digital Single Channel Adjustable Automatic Electronic Pipette Micropipette dPettee+ were purchased from Dragon Laboratory Instruments Limited. Silica gel was purchased from Qing Dao Hai Yang Chemical Industry Co. 1H NMR and 13C NMR spectra were recorded on a Bruker DPX-400 spectrometer in CDCl3. All chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz relative to tetramethylsilane as internal standard (δ = 0 ppm). For the 19F NMR spectra, the chemical shifts δ are reported relative to CFCl3 (δ= 0 ppm) as internal standard. High resolution mass spectra (HRMS) were obtained on an Agilent LC-MSD-Trap-XCT spectrometer with micromass MS software using electrospray ionization (ESI). The Cyclic voltammetry (CV) was recorded in CH3CN by CHI650A. The UV/Vis absorption spectra were recorded on a Perkin Elmer Lambda 35 Spectrometer and the fluorescence emission spectra were recorded using a F-4500 FL spectrophotometer. The X-ray single crystal structure is determined by the Oxford Diffraction Xcalibur CCD single crystal diffractometer.

2. Experimental Procedure

General procedure for the electrochemical synthesis of 2-phenyl-3-tosylimidazo[1,2-a]pyridineCompounds 1 (0.3 mmol), 2 (0.9 mmol, 3.0 equiv.) and MeCN:H2O (2:1, 7 mL) were added in a three-necked flask (10 mL). The reaction mixture was electrolyzed with a C|Ni electrode at a constant current of 5 mA in an undivided cell under air at room temperature for 9 hours. After electrolysis, the reaction mixture was extracted with ethyl acetate, the organic phase was dried over Na2SO4 and concentrated under reduced pressure. The crude products were purified through silica gel column chromatography using dichloromethane/ethyl acetate (30:1, v/v) as eluent to give the corresponding product.

S3

Experimental setup

3. Cyclic Voltammetry Experiments

Cyclic voltammetry was measured under Ar balloon protection with conventional three-electrode system (Reference electrode: Ag/AgCl, working electrode: Glassy carbon, counter electrode: Pt wire, Supporting electrolyte: 0.1 M TBAPF6 in CH3CN)

0.0 0.5 1.0 1.5 2.0 2.5 3.0-0.00005

0.00000

0.00005

0.00010

0.00015

0.00020

Cur

rent

/A

Potential/V(vs Ag/AgCl)

Figure S1. Cyclic voltammograms of sodium naphthalene-2-sulfinate (2h) in CH3CN at 100 mV/s scan rates.

S4

4. Control Experiments

N

N+ S

ONa

O

N

N

SO

O

1a 2a 3aa, 0% (for exp 1)69% (for exp 2)trace (for exp 3)

C(+)|Ni(-), 5 mA,CH3CN/H2O (2:1), 9 h, air, r.t.

OS OO

I

[ I + Na ]+ m/z = 397.1806

O

NNII

[ II + H ]+ m/z = 413.2590

SO

O

[ III ]+m/z = 155.0161

III

exp 1: with 4 equiv. TEMPOexp 2: with 4 equiv. BHTexp 3: with 4 equiv. 1,1-diphenylethene

From exp 2

Scheme S1. Control experiments.

OS OO

Na

Figure S2. HRMS spectrum of compound [I + Na]+ for exp 2

S5

O

NN

H

Figure S3. HRMS spectrum of compound [II + H]+ for exp 2

SO

O

Figure S4. HRMS spectrum of compound [III]+ for exp 2

S6

5. Optical spectroscopy data

(1) The UV/Vis absorption spectra were recorded in CH3CN of a 1x10-5 M solution in 10 mm path length quartz cuvette on a Perkin Elmer Lambda 35 Spectrometer.

225 250 275 300 325 350 375 4000.0

0.1

0.2

0.3

0.4

0.5

Abs

orba

nce

Wavelength/nm

1a 3aa 7 9

Figure S5. Absorption spectra of 1a, 3aa, 7 and 9 in CH3CN

S7

(2) Fluorescence emission spectra were recorded using a F-4500 FL spectrophotometer in CH3CN.

350 400 450 500 550 6000

1000

2000

3000

4000

5000

Fluo

resc

ence

Inte

nsity

Wavelength/nm

1a 3aa 7 9

Figure S6. Fluorescence emission spectra of 1a, 3aa, 7 and 9 in CH3CN

(3) The fluorescence quantum yields of the different samples were calculated using quinine sulfate (QY = 0.55) as the standard (in 0.1 M H2SO4).3

Table S1. Absorption, emission and fluorescence quantum yields (ΦF) of compounds 1a, 3aa, 7 and 9

λabs (nm) λem (nm) ФF1a 247, 326 389 0.433aa 234, 253, 291 440 0.0067 232, 284, 336 411 0.169 231, 276, 317 402 0.08

S8

6. Computational Details

All the calculations were performed using M06-2X method4 and def2-TZVP(D) basis sets5 with the Gaussian 16 program package.6 The polarizable continuum model (PCM)7 was employed to consider the solvent effect of CH3CN/H2O. The intrinsic reaction coordinate (IRC) analysis was carried out to confirm that all the saddle point connected the correct reactant and product on the potential energy surface. With the help of Multiwfn 3.7-dew8 and VMD version 1.9.3 programs,9 we drawn and analysed TS and the Electrostatic potential (ESP) map of 1a.

1aSum of electronic and zero-point Energies= -610.691638Sum of electronic and thermal Energies= -610.681091Sum of electronic and thermal Enthalpies= -610.680146Sum of electronic and thermal Free Energies= -610.729207C -4.14210876 -0.78359072 0.02900009C -4.18393525 0.63758856 -0.02627111C -3.03382465 1.35265674 -0.05258306N -1.83582048 0.69024859 -0.02532515C -1.74914617 -0.69543301 0.02670916C -2.95047621 -1.44168992 0.05515284C -0.55158116 1.16895774 -0.04178485C 0.25913043 0.05710660 0.00148961N -0.48635788 -1.08724595 0.04237687C 1.72817953 0.02212914 0.00247142C 2.39958711 -1.19894801 -0.06066628C 3.78652382 -1.24154277 -0.06359247C 4.52348040 -0.06569606 -0.00335844C 3.86207199 1.15545799 0.06124231C 2.47662321 1.19922608 0.06508479H -5.06927334 -1.33961592 0.05025694H -5.12856632 1.16010159 -0.04769686H -2.98445191 2.43056378 -0.09393232H -2.88539199 -2.51961605 0.09694935H -0.34687084 2.22366282 -0.08762617H 1.82124144 -2.11169959 -0.10861391H 4.29360812 -2.19662757 -0.11396906H 5.60517163 -0.09909505 -0.00558533H 4.42780786 2.07686195 0.11126246H 1.97482805 2.15711130 0.12222875

2kSum of electronic and zero-point Energies= -750.866792Sum of electronic and thermal Energies= -750.860254Sum of electronic and thermal Enthalpies= -750.859310

S9

Sum of electronic and thermal Free Energies= -750.897786S -0.61767100 0.00000100 -0.55797900O 0.22400400 1.22284200 -0.25512100O 0.22402300 -1.22283000 -0.25513500Na 2.08154600 -0.00000100 0.43354600C -1.77302800 -0.00001200 0.82658100H -2.39244200 0.89386700 0.77100800H -2.39243200 -0.89389800 0.77101100H -1.17544300 -0.00000800 1.73919900

ASum of electronic and zero-point Energies= -588.636559Sum of electronic and thermal Energies= -588.632003Sum of electronic and thermal Enthalpies= -588.631059Sum of electronic and thermal Free Energies= -588.663829S -0.40218600 0.17402200 0.00000000O 0.24166200 0.73952700 1.24074000O 0.24166200 0.73952700 -1.24074000C 0.24166200 -1.51816100 0.00000000H -0.10588400 -2.03383000 0.89415300H -0.10588400 -2.03383000 -0.89415300H 1.33018100 -1.44016500 0.00000000

BSum of electronic and zero-point Energies= -588.452309Sum of electronic and thermal Energies= -588.447666Sum of electronic and thermal Enthalpies= -588.446722Sum of electronic and thermal Free Energies= -588.480365S 0.28058000 0.17840900 0.00000000O -0.16910800 0.75653200 1.25489100O -0.16910800 0.75653200 -1.25489100C -0.16910800 -1.56100800 0.00000000H 0.24442600 -2.00310100 -0.90109200H 0.24442600 -2.00310100 0.90109200H -1.25776200 -1.58680900 0.00000000

CSum of electronic and zero-point Energies= -588.220815Sum of electronic and thermal Energies= -588.215953Sum of electronic and thermal Enthalpies= -588.215009Sum of electronic and thermal Free Energies= -588.248874S -0.00786100 0.16688200 0.00000000O 0.00209200 0.78336100 1.25502700O 0.00209200 0.78336100 -1.25502700

S10

C 0.00209200 -1.59245200 0.00000000H 1.06467600 -1.85442500 0.00000000H -0.49246600 -1.89738100 0.91896500H -0.49246600 -1.89738100 -0.91896500

DSum of electronic and zero-point Energies= -1199.145976Sum of electronic and thermal Energies= -1199.130072Sum of electronic and thermal Enthalpies= -1199.129127Sum of electronic and thermal Free Energies= -1199.190878C -3.83903400 -1.90193800 0.02157500C -4.00000000 -0.72613100 -0.76750200C -2.91906500 0.04162500 -1.04847600N -1.69657300 -0.33618000 -0.57778700C -1.48664200 -1.49404900 0.16339700C -2.61238500 -2.28345900 0.47956100C -0.43784100 0.34699000 -0.70333300C 0.49358800 -0.67846800 -0.12438000N -0.20610900 -1.68953000 0.43311500C 1.92900100 -0.63117100 -0.15745600C 2.62448300 0.34707200 -0.88909800C 4.00842000 0.34614000 -0.92987700C 4.73589600 -0.61925100 -0.24198600C 4.05868500 -1.59355800 0.48790000C 2.67732600 -1.60542900 0.53037700S -0.50971600 1.92169800 0.30723500O 0.74526100 2.61316800 0.14107300O -1.72690000 2.61227200 -0.05421700H -4.70746300 -2.50393000 0.25240000H -4.96951000 -0.43756200 -1.14264500H -2.95220500 0.95441000 -1.62372600H -2.46634500 -3.17750800 1.06803200H -0.22987400 0.72303200 -1.70927400H 2.07960600 1.11361300 -1.42326100H 4.52439400 1.10564400 -1.50329000H 5.81735000 -0.61390200 -0.27399600H 4.61596200 -2.34967700 1.02636400H 2.15198000 -2.36531000 1.09264200C -0.64904800 1.35150600 1.97320300H -0.75421900 2.24754300 2.58296400H -1.53700400 0.72783900 2.05827900H 0.25439200 0.80582400 2.23415200

E

S11

Sum of electronic and zero-point Energies= -1198.996016Sum of electronic and thermal Energies= -1198.980468Sum of electronic and thermal Enthalpies= -1198.979524Sum of electronic and thermal Free Energies= -1199.039548C -3.93281300 -1.78586500 0.04159500C -4.08875000 -0.55569200 -0.60091500C -2.98304100 0.20409300 -0.88833700N -1.77409000 -0.26868700 -0.53337800C -1.58832300 -1.47209000 0.07251500C -2.67836000 -2.26034200 0.38230600C -0.47830600 0.35954800 -0.69992900C 0.43004300 -0.74443500 -0.19858400N -0.25028100 -1.73931600 0.26801200C 1.88111900 -0.68632200 -0.19812700C 2.56981500 0.20500200 -1.02484000C 3.95465500 0.21142300 -1.02614900C 4.65394300 -0.65849900 -0.19965900C 3.97192600 -1.54591800 0.62844900C 2.59090900 -1.56667400 0.62766100S -0.37511800 1.90255600 0.31662700O 0.86753800 2.51847800 -0.03952900O -1.61034300 2.59538900 0.08651300H -4.80633300 -2.38188600 0.26755200H -5.06447800 -0.19104800 -0.88194100H -3.01085100 1.16318900 -1.38191000H -2.52504600 -3.21292900 0.86570400H -0.30300900 0.69709300 -1.72222600H 2.03339100 0.88472800 -1.67225700H 4.48785100 0.89473300 -1.67256400H 5.73601600 -0.64678300 -0.19955800H 4.52125500 -2.21859900 1.27278200H 2.04576300 -2.24908400 1.26560200C -0.31623800 1.33215900 1.97869400H -0.32067100 2.23578200 2.58766900H -1.20324100 0.73721100 2.18835500H 0.60482700 0.77343400 2.13037200

FSum of electronic and zero-point Energies= -610.472812Sum of electronic and thermal Energies= -610.462189Sum of electronic and thermal Enthalpies= -610.461245Sum of electronic and thermal Free Energies= -610.510702C -4.13104803 -0.76123803 0.01554482C -4.18166509 0.64570233 -0.01239955

S12

C -3.02653517 1.36300132 -0.02706617N -1.84037832 0.68071861 -0.01384428C -1.75896877 -0.70271505 0.01218663C -2.92585795 -1.44197693 0.02776727C -0.56882676 1.15594304 -0.02166906C 0.27651568 -0.01394745 0.00189205N -0.46085858 -1.10455368 0.02024943C 1.72821464 -0.00473619 0.00121856C 2.42362525 -1.21868659 -0.03011636C 3.80501722 -1.22126086 -0.03184925C 4.50478877 -0.01724655 -0.00121825C 3.82011525 1.19097797 0.03172437C 2.43557723 1.20094808 0.03259970H -5.05557543 -1.32161076 0.02773266H -5.12721868 1.16502642 -0.02222058H -2.96444533 2.44039454 -0.04807490H -2.87112609 -2.51986836 0.04904831H -0.35206971 2.21044023 -0.04689644H 1.86690827 -2.14549699 -0.05465278H 4.34262006 -2.15938158 -0.05773583H 5.58685543 -0.02315960 -0.00299895H 4.36484299 2.12473873 0.05707189H 1.91215313 2.14717230 0.06220206

GSum of electronic and zero-point Energies= -610.004525Sum of electronic and thermal Energies= -609.993958Sum of electronic and thermal Enthalpies= -609.993014Sum of electronic and thermal Free Energies= -610.042732C 4.15579489 0.74253065 -0.00000384C 4.18711634 -0.68118426 0.00001798C 3.03513189 -1.39157106 0.00002274N 1.84306654 -0.71331457 0.00000809C 1.76299606 0.67859228 -0.00001272C 2.97129728 1.41307140 -0.00001976C 0.55497453 -1.14323890 0.00000675C -0.27129788 -0.05063936 -0.00000910N 0.50194904 1.08093894 -0.00002202C -1.73487183 -0.02360375 -0.00000556C -2.42061622 1.18972795 0.00001878C -3.80831939 1.20876770 0.00002663C -4.52521139 0.01901370 0.00001007C -3.84580800 -1.19464520 -0.00001642C -2.46054967 -1.21587370 -0.00002587

S13

H 5.08784899 1.29045484 -0.00000801H 5.12871757 -1.20948257 0.00003025H 2.97304313 -2.46925173 0.00003774H 2.91579763 2.49258856 -0.00003767H -1.85608658 2.11265616 0.00003432H -4.33169523 2.15624188 0.00004704H -5.60727659 0.03554694 0.00001691H -4.39790774 -2.12553918 -0.00003132H -1.93136985 -2.16227010 -0.00004980

3akSum of electronic and zero-point Energies= -1198.588561Sum of electronic and thermal Energies= -1198.573201Sum of electronic and thermal Enthalpies= -1198.572257Sum of electronic and thermal Free Energies= -1198.632238C -3.89166100 -2.03726700 -0.09595100C -4.09284900 -0.63627300 -0.16239500C -3.03423500 0.21156100 -0.19112900N -1.76646700 -0.30713000 -0.14510100C -1.53218000 -1.66682600 -0.07669800C -2.63008000 -2.55033300 -0.05749100C -0.51663700 0.29964400 -0.15483100C 0.40634900 -0.74000800 -0.08956300N -0.22847300 -1.93092300 -0.04416700C 1.87942800 -0.69785800 -0.07508100C 2.56239600 -1.49693000 0.84137900C 3.94901200 -1.51670700 0.85632100C 4.66481200 -0.75056700 -0.05540600C 3.98861100 0.03299900 -0.98200200C 2.60157200 0.06145500 -0.99280300H -4.74778800 -2.69728800 -0.07990200H -5.08963500 -0.22331400 -0.19973200H -3.11812600 1.28377000 -0.26939000H -2.43250300 -3.61131700 -0.00997800H 1.99754500 -2.09763800 1.54256400H 4.47076500 -2.13173800 1.57786000H 5.74696700 -0.76872500 -0.04771700H 4.54239000 0.62041100 -1.70272900H 2.07523800 0.66659800 -1.71755200S -0.35295100 2.01791300 0.03930900O -1.33384200 2.66067900 -0.80261300O 1.03087600 2.37061500 -0.12325500C -0.80861600 2.31172700 1.71911500H -0.78213900 3.39180300 1.85805800

S14

H -1.81533500 1.93317800 1.88670200H -0.08739400 1.81596600 2.36388300

TS1

2.472.44

Sum of electronic and zero-point Energies= -1198.936426Sum of electronic and thermal Energies= -1198.920979Sum of electronic and thermal Enthalpies= -1198.920035Sum of electronic and thermal Free Energies= -1198.979282C -4.11218600 -0.42367000 0.94410900C -4.14287500 -1.19297900 -0.25247400C -2.99985500 -1.52626800 -0.89609100N -1.80474000 -1.11011800 -0.36495500C -1.73536900 -0.36988200 0.80956400C -2.92968000 -0.00932300 1.47094700C -0.54001300 -1.28953200 -0.82636100C 0.29322100 -0.65616800 0.08326500N -0.47984900 -0.06784700 1.09614400C 1.75185900 -0.71392400 0.16753100C 2.50781100 -1.10035800 -0.94050700C 3.88842700 -1.14350400 -0.85355500C 4.52392400 -0.79981200 0.33505000C 3.77464700 -0.41409400 1.43866800C 2.39080300 -0.37049800 1.35911600S -0.07939900 1.64894000 -0.63217000O 1.01513900 1.62258100 -1.53322000O -1.43543100 1.66612300 -1.04747600H -5.04294300 -0.17081600 1.43160300H -5.08555900 -1.52018700 -0.66512800H -2.94838300 -2.10028500 -1.80814500H -2.86184900 0.57643000 2.37602200H -0.33092500 -1.85604900 -1.71690600H 2.01904600 -1.35257400 -1.87305100H 4.47142700 -1.44132500 -1.71460000H 5.60345600 -0.83397500 0.39938300H 4.26720100 -0.15125900 2.36520900H 1.79863400 -0.08564300 2.21894100C 0.27713900 2.66726700 0.76737600H 1.17770100 2.26052100 1.22142500H 0.45335700 3.65656100 0.34173200H -0.58344700 2.62814800 1.42564000

S15

TS2

2.20

Sum of electronic and zero-point Energies= -1199.143520Sum of electronic and thermal Energies= -1199.127510Sum of electronic and thermal Enthalpies= -1199.126566Sum of electronic and thermal Free Energies= -1199.190167C -3.94758200 -1.74097100 0.19896800C -4.05545100 -0.63222300 -0.68211300C -2.93679000 0.01851100 -1.08836500N -1.72126600 -0.42465900 -0.65474500C -1.57200000 -1.50593200 0.20134600C -2.72860900 -2.17376700 0.63965000C -0.45349200 0.12114400 -0.86931600C 0.42137300 -0.82717300 -0.22589100N -0.28581500 -1.74580200 0.45590300C 1.87149500 -0.76906500 -0.22500900C 2.54800900 0.27736600 -0.86343100C 3.93310200 0.33168700 -0.84486900C 4.66362500 -0.65289800 -0.19095500C 3.99850500 -1.69506000 0.44822700C 2.61591500 -1.75488900 0.43444600H -4.84660200 -2.24747300 0.52226000H -5.01948500 -0.29461100 -1.03044500H -2.93223000 0.87640900 -1.74379100H -2.61931300 -3.01468100 1.30881600H -0.25528700 0.61374700 -1.81400900H 1.99273800 1.05918800 -1.36775500H 4.44342300 1.14666600 -1.34129100H 5.74466900 -0.60862900 -0.17743500H 4.56334900 -2.46368500 0.95972700H 2.09365700 -2.56215000 0.92997000S -0.44483600 1.99368900 0.29149900O 0.37573100 2.98228500 -0.39497000O -1.83144700 2.34077100 0.57496200C 0.34141400 1.60170000 1.84162700H 0.28276500 2.50420400 2.44877400H -0.20686300 0.78337200 2.30368200H 1.37476000 1.32682100 1.64356100

H2O

S16

Sum of electronic and zero-point Energies= -76.412226Sum of electronic and thermal Energies= -76.409391Sum of electronic and thermal Enthalpies= -76.408447Sum of electronic and thermal Free Energies= -76.429870O 0.00000000 0.00000000 0.11737400H 0.00000000 -0.76221000 -0.46949600H 0.00000000 0.76221000 -0.46949600

H-cationSum of electronic and zero-point Energies= -0.163351Sum of electronic and thermal Energies= -0.161935Sum of electronic and thermal Enthalpies= -0.160991Sum of electronic and thermal Free Energies= -0.173351H 0.00000000 0.00000000 0.00000000

OH-anionSum of electronic and zero-point Energies= -75.916164Sum of electronic and thermal Energies= -75.913804Sum of electronic and thermal Enthalpies= -75.912860Sum of electronic and thermal Free Energies= -75.932410O 0.00000000 0.00000000 0.10682400H 0.00000000 0.00000000 -0.85459600

S17

7. Characterization Data

2-phenyl-3-tosylimidazo[1,2-a]pyridine (3aa)10,11,12

N

N

S OO

White solid (84.9 mg, 81%). mp. 137.2-138.3 oC. 1H NMR (400 MHz, CDCl3): δ 9.11 (dt, J1 = 7.09 Hz, J2 = 1.10 Hz, 1H), 7.77-7.69 (m, 3H), 7.55-7.50 (m, 2H), 7.49-7.41 (m, 4H), 7.14 (d, J = 8.07 Hz, 2H), 7.05 (td, J1 = 6.97 Hz, J2 = 1.22 Hz, 1H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.8, 146.6, 144.4, 139.0, 132.7, 130.5, 129.7, 129.3, 128.5, 127.8, 126.8, 126.4, 118.0, 117.8, 114.6, 21.5. HRMS (ESI) calcd. for C20H16N2O2S (M+H)+: 349.1005, found: 349.1006.

2-phenyl-3-(phenylsulfonyl)imidazo[1,2-a]pyridine (3ab)10,12,13

N

N

S OO

White solid (80.3 mg, 80%). mp. 123.9-124.8 oC. 1H NMR (400 MHz, CDCl3): δ 9.14 (d, J = 7.03 Hz, 1H), 7.73 (d, J = 8.03 Hz, 3H), 7.63 (d, J = 7.78 Hz, 2H), 7.47 (br. s., 5H), 7.38-7.31 (m, 2H), 7.07 (t, J = 6.78 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 153.1, 146.7, 141.9, 133.4, 132.5, 130.5, 129.4, 129.1, 128.6, 127.8, 126.9, 126.3, 118.0, 117.4, 114.7. HRMS (ESI) calcd. for C19H14N2O2S

(M+H)+: 335.0849, found: 335.0850.

3-((4-methoxyphenyl)sulfonyl)-2-phenylimidazo[1,2-a]pyridine (3ac)10

N

N

S OO

OCH3

White solid (88.2mg, 81%). mp. 138.7-139.0 oC. 1H NMR (400 MHz, CDCl3): δ 9.10 (d, J = 7.03 Hz, 1H), 7.77-7.72 (m, 2H), 7.70 (d, J = 9.03 Hz, 1H), 7.60-7.55 (m, 2H), 7.48-7.40 (m, 4H), 7.03 (td, J1 = 7.03 Hz, J2 = 1.00 Hz, 1H), 6.81-6.76 (m, 2H), 3.75 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 163.5, 152.3, 146.4, 133.4, 132.7, 130.5, 129.3, 128.7, 128.4, 127.8, 126.8, 118.2, 117.9, 114.6, 114.3, 55.6. HRMS (ESI) calcd. for C20H16N2O3S (M+H)+: 365.0954, found: 365.0955.

3-((4-(tert-butyl)phenyl)sulfonyl)-2-phenylimidazo[1,2-a]pyridine (3ad)12

S18

N

N

S OO

White solid (88.3 mg, 75%). mp. 149.9-150.3 oC. 1H NMR (400 MHz, CDCl3): δ 9.13 (d, J = 7.03 Hz, 1H), 7.76-7.70 (m, 3H), 7.57 (d, J = 8.53 Hz, 2H), 7.49-7.43 (m, 4H), 7.35 (d, J = 8.78 Hz, 2H), 7.06 (td, J1 = 6.90 Hz, J2 = 1.00 Hz, 1H), 1.25 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 157.3, 152.7, 146.6, 138.9, 132.7, 130.5, 129.3, 128.5, 127.8, 126.9, 126.3, 126.1, 118.0, 117.9, 114.6, 35.2, 30.9. HRMS (ESI) calcd. for C23H22N2O2S (M+H)+: 391.1475, found: 391.1474.

3-((4-fluorophenyl)sulfonyl)-2-phenylimidazo[1,2-a]pyridine (3ae)10,12

N

N

S OO

FWhite solid (88.6mg, 84%). mp. 125.5-127.6 oC. 1H NMR (400 MHz, CDCl3): δ 9.14 (d, J = 7.03 Hz, 1H), 7.77-7.68 (m, 3H), 7.65-7.58 (m, 2H), 7.52-7.42 (m, 4H), 7.08 (t, J = 7.03 Hz, 1H), 7.03-6.95 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 166.7, 164.2, 153.1, 146.7, 138.0, 132.4, 130.5, 129.5, 129.2, 128.7, 127.9, 126.8, 118.1, 117.4, 116.4, 116.2, 114.8. 19F NMR (376 MHz, CDCl3): δ -103.67. HRMS (ESI) calcd. for C19H13FN2O2S (M+H)+: 353.0755, found: 353.0756.

3-((4-chlorophenyl)sulfonyl)-2-phenylimidazo[1,2-a]pyridine (3af)10,11

N

N

S OO

ClWhite solid (47.7 mg, 43%). mp. 120.2-121.4 oC. 1H NMR (400 MHz, CDCl3): δ 9.13 (d, J = 6.78 Hz, 1H), 7.79-7.66 (m, 3H), 7.57-7.41 (m, 6H), 7.29 (d, J = 8.28 Hz, 2H), 7.09 (t, J = 6.78 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 153.3, 146.8, 140.4, 140.0, 132.3, 130.5, 129.6, 129.3, 128.8, 127.9, 127.8, 126.8, 118.1, 117.2, 114.9. HRMS (ESI) calcd. for C19H13ClN2O2S (M+H)+: 369.0459, found: 369.0460.

2-phenyl-3-((4-(trifluoromethyl)phenyl)sulfonyl)imidazo[1,2-a]pyridine (3ag)10,12

S19

N

N

S OO

CF3

White solid (106 mg, 87%). mp. 137.6-138.1 oC. 1H NMR (400 MHz, CDCl3): δ 9.16 (d, J = 7.03 Hz, 1H), 7.77-7.67 (m, 5H), 7.58 (d, J = 8.28 Hz, 2H), 7.53-7.43 (m, 4H), 7.10 (t, J = 6.90 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 153.9, 147.0, 145.4, 135.0, 134.7, 132.3, 130.5, 129.7, 129.1, 128.0, 126.8, 126.2, 124.4, 121.6, 118.2, 116.6, 115.0. 19F NMR (376 MHz, CDCl3): δ -63.28. HRMS (ESI) calcd. for C20H13F3N2O2S (M+H)+: 403.0723.0738, found: 403.0722.

2-phenyl-3-(thiophen-2-ylsulfonyl)imidazo[1,2-a]pyridine (3ai)

N

N

S OO

S

White solid (97.7 mg, 95%). mp. 186.8-187.7 oC. 1H NMR (400 MHz, CDCl3): δ 9.07 (d, J = 7.03 Hz, 1H), 7.81-7.72 (m, 3H), 7.53-7.43 (m, 6H), 7.09 (td, J1 = 7.03 Hz, J2 = 1.00 Hz, 1H), 6.95 (dd, J1 = 4.89 Hz, J2 = 3.89 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 152.9, 146.7, 143.4, 133.2, 132.6, 132.3, 130.5, 129.4, 128.8, 127.8, 127.6, 126.9, 118.1, 117.8, 114.8. HRMS (ESI) calcd. for C17H12N2O2S2 (M+H)+: 341.0413, found: 341.0416.

2-phenyl-3-(pyridin-3-ylsulfonyl)imidazo[1,2-a]pyridine (3aj)

N

N

S OO

N

Yellow solid (88.9 mg, 88%). mp. 130.8-131.4 oC. 1H NMR (400 MHz, CDCl3): δ 9.22-9.14 (m, 1H), 8.84 (s, 1H), 8.71-8.63 (m, 1H), 7.81-7.67 (m, 4H), 7.54-7.42 (m, 4H), 7.27-7.22 (m, 1H), 7.15-7.08 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 153.8, 147.3, 147.0, 138.5, 133.9, 132.2, 130.5, 129.7, 129.1, 128.0, 126.8, 123.6, 118.2, 116.8, 115.1. HRMS (ESI) calcd. for C18H13N3O2S (M+H)+: 336.0801, found: 336.0805.

3-(methylsulfonyl)-2-phenylimidazo[1,2-a]pyridine (3ak)

N

N

S OO

CH3

S20

White solid (66.5 mg, 81%). mp. 186.9-187.9 oC. 1H NMR (400 MHz, CDCl3): δ 9.11 (d, J = 7.03 Hz, 1H), 7.91-7.85 (m, 2H), 7.78 (d, J = 9.03 Hz, 1H), 7.53-7.46 (m, 4H), 7.08 (t, J = 6.78 Hz, 1H), 3.03 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 151.9, 146.5, 132.4, 130.2, 129.6, 128.6, 128.3, 127.1, 118.0, 117.0, 114.7, 45.0. HRMS (ESI) calcd. for C14H12N2O2S (M+H)+: 273.0692, found: 273.0689.

6-methyl-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ba)

N

N

S OO

White solid (99.3 mg, 91%). mp. 148.7-149.7 oC. 1H NMR (400 MHz, CDCl3): δ 8.89 (s, 1H), 7.74-7.68 (m, 2H), 7.61 (d, J = 9.29 Hz, 1H), 7.52 (d, J = 8.28 Hz, 2H), 7.47-7.42 (m, 3H), 7.29 (dd, J1 = 9.16 Hz, J2 = 1.38 Hz, 1H), 7.14 (d, J = 8.03 Hz, 2H), 2.42 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.6, 145.6, 144.3, 139.2, 132.8, 131.5, 130.5, 129.6, 129.2, 127.7, 126.4, 124.6, 117.3, 117.2, 21.5, 18.6. HRMS (ESI) calcd. for C21H18N2O2S (M+H)+: 363.1162, found: 363.1164.

6-methoxy-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ca)

N

N

S OO

MeO

White solid (81.7 mg, 72%). mp. 174.8-175.3 oC. 1H NMR (400 MHz, CDCl3): δ 8.68 (s, 1H) 7.72 (d, J = 4.02 Hz, 2H), 7.58 (d, J = 9.79 Hz, 1H), 7.51 (d, J = 8.03 Hz, 2H), 7.44 (d, J = 3.51 Hz, 3H), 7.21 (dd, J1 = 9.54 Hz, J2 = 1.76 Hz, 1H), 7.13 (d, J = 7.78 Hz, 2H), 3.91 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.4, 150.4, 144.4, 143.4, 139.0, 132.8, 130.5, 129.6, 129.2, 127.7, 126.4, 123.2, 118.2, 117.9, 108.9, 56.4, 21.5. HRMS (ESI) calcd. for C21H18N2O3S (M+H)+: 379.1111, found: 379.1113.

6-fluoro-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3da)

N

N

S OO

F

S21

White solid (93.0 mg, 85%). mp. 144.1-145.9 oC. 1H NMR (400 MHz, CDCl3): δ 9.13 (dd, J1 = 4.64 Hz, J2 = 2.13 Hz, 1H), 7.74-7.65 (m, 3H), 7.51 (d, J = 8.53 Hz, 2H), 7.48-7.42 (m, 3H), 7.36 (ddd, J1 = 9.85 Hz, J2 = 7.47 Hz, J3 = 2.51 Hz, 1H), 7.14 (d, J = 8.28 Hz, 2H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 155.1, 153.4, 152.8, 144.7, 144.1, 138.7, 132.4, 130.4, 129.8, 129.5, 127.9, 126.4, 120.4, 120.1, 119.2, 118.4, 114.5, 114.1, 21.6. 19F NMR (376 MHz, CDCl3): δ -135.38. HRMS (ESI) calcd. for C20H15FN2O2S (M+H)+: 367.0911, found: 367.0912.

6-chloro-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ea)

N

N

S OO

Cl

White solid (76.0 mg, 66%). mp. 173.7-174.2 oC. 1H NMR (400 MHz, CDCl3): δ 9.22 (d, J = 1.00 Hz, 1H), 7.71 (dd, J1 = 7.65 Hz, J2 = 1.63 Hz, 2H), 7.65 (d, J = 9.54 Hz, 1H), 7.52-7.40 (m, 6H), 7.15 (d, J = 8.03 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.1, 144.8, 144.7, 138.7, 132.2, 130.5, 129.8, 129.5, 127.9, 126.5, 124.8, 122.9, 118.6, 118.2, 21.6. HRMS (ESI) calcd. for C20H15ClN2O2S (M+H)+: 383.0616, found: 383.0614.

6-bromo-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3fa)

N

N

S OO

Br

White solid (56.3 mg, 44%). mp. 174.2-174.7 oC. 1H NMR (400 MHz, CDCl3): δ 9.31 (s, 1H), 7.67-7.74 (m, 2H), 7.62-7.57 (m, 1H), 7.53-7.42 (m, 6H), 7.15 (d, J = 8.28 Hz, 2H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.9, 144.9, 144.7, 138.7, 132.2, 131.9, 130.5, 129.8, 129.5, 127.9, 126.9, 126.5, 118.5, 109.4, 21.6. HRMS (ESI) calcd. for C20H15BrN2O2S (M+H)+: 427.0110, found: 427.0110.

2-phenyl-3-tosyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine (3ga)

N

N

S OO

F3C

White solid (52.4 mg, 42%). mp. 169.5-170.1 oC. 1H NMR (400 MHz, CDCl3): δ 9.55 (s, 1H), 7.81 (d, J = 9.29 Hz, 1H), 7.76-7.70 (m, 2H), 7.60 (d, J = 9.54 Hz, 1H), 7.53-7.44 (m, 5H), 7.15 (d, J =

S22

8.03 Hz, 2H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.9, 146.2, 145.0, 138.4, 131.9, 130.5, 129.8, 127.9, 126.6, 126.0, 124.5, 124.3, 121.8, 119.6, 119.0, 118.7, 21.5. 19F NMR (376 MHz, CDCl3): δ -62.01. HRMS (ESI) calcd. for C21H15F3N2O2S (M+H)+: 417.0879, found: 417.0881.

7-methyl-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ha)

N

N

S OO

White solid (100.5 mg, 92%). mp. 157.6-158.1 oC. 1H NMR (400 MHz, CDCl3): δ 8.96 (d, J = 7.03 Hz, 1H), 7.77-7.71 (m, 2H), 7.51 (d, J = 8.28 Hz, 2H), 7.48-7.42 (m, 4H), 7.12 (d, J = 8.03 Hz, 2H), 6.87 (dd, J1 = 7.15 Hz, J2 = 1.63 Hz, 1H), 2.44 (s, 3H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.9, 147.0, 144.2, 140.1, 139.2, 132.7, 130.5, 129.7, 129.3, 127.7, 126.3, 125.9, 117.1, 116.5, 21.5, 21.4. HRMS (ESI) calcd. for C21H18N2O2S (M+H)+: 363.1162, found: 363.1164.

7-methoxy-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ia)

N

N

S OO

MeO

White solid (100.1 mg, 88%). mp. 159.2-160.8 oC. 1H NMR (400 MHz, CDCl3): δ 8.90 (d, J = 7.53 Hz, 1H), 7.79-7.73 (m, 2H), 7.53-7.42 (m, 5H), 7.13 (d, J = 8.28 Hz, 2H), 6.95 (d, J = 2.51 Hz, 1H), 6.71 (dd, J1 = 7.65 Hz, J2 = 2.38 Hz, 1H), 3.86 (s, 3H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.4, 153.2, 148.7, 144.2, 139.4, 132.7, 130.5, 129.7, 129.3, 127.7, 127.2, 126.2, 116.5, 109.1, 95.5, 55.8, 21.5. HRMS (ESI) calcd. for C21H18N2O3S (M+H)+: 379.1111, found: 379.1109.

7-chloro-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ja)11

N

N

S OO

Cl

White solid (51.1 mg, 42%). mp. 179.5-180.4 oC. 1H NMR (400 MHz, CDCl3): δ 9.06 (d, J = 7.53 Hz, 1H), 7.71 (dd, J1 = 7.53 Hz, J2 = 6.02 Hz, 3H), 7.52-7.43 (m, 5H), 7.13 (d, J = 8.03 Hz, 2H), 7.03 (dd, J1 = 7.28 Hz, J2 = 1.51 Hz, 1H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.4, 146.4, 144.7, 138.8, 135.4, 132.2, 130.5, 129.8, 129.6, 127.9, 127.2, 126.4, 118.3, 116.9, 116.1, 21.5. HRMS (ESI) calcd. for C20H15ClN2O2S (M+H)+: 383.0616, found: 383.0620.

S23

8-methyl-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ka)

N

N

S OO

White solid (98.0 mg, 90%). mp. 161.5-162.3 oC. 1H NMR (400 MHz, CDCl3): δ 8.96 (d, J = 6.78 Hz, 1H), 7.76-7.69 (m, 2H), 7.52 (d, J = 8.03 Hz, 2H), 7.48-7.42 (m, 3H), 7.23 (d, J = 7.03 Hz, 1H), 7.13 (d, J = 8.03 Hz, 2H), 6.95 (t, J = 6.90 Hz, 1H), 2.63 (s, 3H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.3, 146.8, 144.2, 139.2, 133.0, 130.6, 129.6, 129.2, 128.1, 127.8, 127.3, 126.4, 124.5, 118.1, 114.6, 21.5, 17.1. HRMS (ESI) calcd. for C21H18N2O2S (M+H)+: 363.1162, found: 363.1166.

8-chloro-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3la)

N

N

S OO

Cl

White solid (100.8 mg, 87%). mp. 151.7-152.2 oC. 1H NMR (400 MHz, CDCl3): δ 9.09 (d, J = 6.78 Hz, 1H), 7.72 (d, J = 6.27 Hz, 2H), 7.55-7.41 (m, 6H), 7.13 (d, J = 8.03 Hz, 2H), 7.00 (t, J = 7.15 Hz, 1H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.9, 144.7, 143.9, 138.7, 132.2, 130.7, 129.7, 129.5, 127.8, 127.3, 126.5, 125.5, 123.9, 119.8, 114.2, 21.5. HRMS (ESI) calcd. for C20H15ClN2O2S (M+H)+: 383.0616, found: 383.0619.

8-bromo-2-phenyl-3-tosylimidazo[1,2-a]pyridine (3ma)

N

N

S OO

Br

White solid (68.6 mg, 53%). mp. 180.4-181.1 oC. 1H NMR (400 MHz, CDCl3): δ 9.13 (d, J = 7.03 Hz, 1H), 7.74-7.67 (m, 3H), 7.51-7.42 (m, 5H), 7.13 (d, J = 8.28 Hz, 2H), 6.93 (t, J = 7.28 Hz, 1H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.9, 144.7, 144.4, 138.7, 132.3, 130.8, 129.7, 129.5, 127.8, 126.5, 126.1, 119.8, 114.5, 112.0, 21.5. HRMS (ESI) calcd. for C20H15BrN2O2S (M+H)+: 427.0110, found: 427.0107.

S24

2-(p-tolyl)-3-tosylimidazo[1,2-a]pyridine (3na)

N

N

S OO

White solid (100.6 mg, 92%). mp. 188.4-189.6 oC. 1H NMR (400 MHz, CDCl3): δ 9.08 (dt, J1 = 7.02 Hz, J2 = 1.14 Hz, 1H), 7.70 (dt, J1 = 9.00 Hz, J1 = 1.14 Hz, 1H), 7.66 (d, J = 8.09 Hz, 2H), 7.54 (d, J = 8.39 Hz, 2H), 7.43 (ddd, J1 = 8.96 Hz, J2 = 6.98 Hz, J3 = 1.30 Hz, 1H), 7.29-7.25 (m, 2H), 7.15 (d, J = 7.93 Hz, 2H), 7.03 (td, J1 = 6.94 Hz, J2 = 1.22 Hz, 1H), 2.44 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.9, 146.5, 144.4, 139.4, 139.1, 130.5, 129.7, 129.6, 128.5, 126.8, 126.4, 117.9, 117.5, 114.5, 21.5. HRMS (ESI) calcd. for C21H18N2O2S (M+H)+: 363.1162, found: 363.1163.

2-(4-methoxyphenyl)-3-tosylimidazo[1,2-a]pyridine (3oa)

N

N

S OO

OCH3

White solid (101.8 mg, 90%). mp. 137.2-138.6 oC. 1H NMR (400 MHz, CDCl3): δ 9.09 (d, J = 7.03 Hz, 1H), 7.74 (d, J = 8.78 Hz, 2H), 7.69 (d, J = 9.03 Hz, 1H), 7.53 (d, J = 8.28 Hz, 2H), 7.43 (t, J = 7.65 Hz, 1H), 7.14 (d, J = 8.03 Hz, 2H), 7.06-6.96 (m, 3H), 3.89 (s, 3H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 160.6, 152.7, 146.6, 144.3, 139.1, 132.0, 129.7, 128.5, 126.8, 126.3, 124.9, 117.8, 117.2, 114.4, 113.3, 55.3, 21.5. HRMS (ESI) calcd. for C21H18N2O3S (M+H)+: 379.1111, found: 379.1109.

2-(4-fluorophenyl)-3-tosylimidazo[1,2-a]pyridine (3pa)

N

N

S OO

F

White solid (100.2 mg, 91%). mp. 171.3-172.6 oC. 1H NMR (400 MHz, CDCl3): δ 9.10 (d, J = 7.03 Hz, 1H), 7.79-7.74 (m, 2H), 7.70 (d, J = 9.03 Hz, 1H), 7.52 (d, J = 8.28 Hz, 2H), 7.49-7.43 (m, 1H), 7.20-7.12 (m, 4H), 7.06 (td, J1 = 6.90, J2 = 1.25 Hz, 1H), 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 164.9, 162.4, 151.7, 146.6, 144.5, 139.0, 132.6, 132.5, 129.8, 128.7, 128.6, 126.8, 126.3, 118.0, 117.8, 115.0, 114.8, 114.7, 21.5. 19F NMR (376 MHz, CDCl3): δ -111.86. HRMS (ESI) calcd. for C20H15FN2O2S (M+H)+: 367.0911, found: 367.0915.

S25

2-(4-chlorophenyl)-3-tosylimidazo[1,2-a]pyridine (3qa)

N

N

S OO

Cl

White solid (95 mg, 83%). mp. 177.8-178.0 oC. 1H NMR (400 MHz, CDCl3): δ 9.09 (d, J = 6.78 Hz, 1H), 7.76-7.68 (m, 3H), 7.53 (d, J = 8.03 Hz, 2H), 7.49-7.41 (m, 3H), 7.17 (d, J = 8.03 Hz, 2H), 7.06 (t, J = 6.78 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 151.4, 146.6, 144.6, 138.9, 135.6, 131.9, 131.1, 129.8, 128.7, 128.1, 126.8, 126.4, 118.0, 117.9, 114.7, 21.5. HRMS (ESI) calcd. for C20H15ClN2O2S (M+H)+: 383.0616, found: 383.0620.

3-tosyl-2-(4-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridine (3ra)

N

N

S OO

CF3

White (22.9 mg, 18%). mp. 201.9-202.2 oC.1H NMR (400 MHz, CDCl3): δ 9.09 (d, J = 7.03 Hz, 1H), 7.89 (d, J = 8.03 Hz, 2H), 7.75-7.70 (m, 3H), 7.54 (d, J = 8.28 Hz, 2H), 7.51-7.45 (m, 1H), 7.17 (d, J = 8.03 Hz, 2H), 7.09 (td, J1 = 6.96, J2 = 1.13 Hz, 1H), 2.34 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 150.9, 146.7, 144.8, 138.7, 136.3, 131.3, 131.0, 129.9, 128.8, 126.8, 126.4, 125.5, 124.7, 122.8, 118.3, 118.1, 114.9, 21.5. 19F NMR (376 MHz, CDCl3): δ -62.64. HRMS (ESI) calcd. for C21H15F3N2O2S (M+H)+: 417.0879, found: 417.0881.

(E)-2-phenyl-8-styryl-3-tosylimidazo[1,2-a]pyridine (7)

N

N

S OO

White (90.1 mg, 73%). mp. 175.8-176.9 oC. 1H NMR (400 MHz, CDCl3): δ 9.00 (d, J = 6.6 Hz, 1H), 7.89-7.78 (m, 3H), 7.63-7.56 (m, 4H), 7.53 (d, J = 8.3 Hz, 2H), 7.51-7.46 (m, 3H), 7.38-7.32 (m, 2H), 7.30-7.24 (m, 1H), 7.13 (d, J = 8.1 Hz, 2H), 7.05 (t, J = 7.2 Hz, 1H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 152.4, 145.2, 144.4, 139.0, 136.9, 134.2, 132.9, 130.8, 129.7, 129.3, 128.7, 128.4, 127.8, 127.4, 127.2, 126.4, 124.9, 124.4, 122.3, 118.1, 114.7, 21.6. HRMS (ESI) calcd. for C28H22N2O2S (M+H)+: 451.1475, found: 451.1477.

S26

2-phenyl-8-(phenylethynyl)-3-tosylimidazo[1,2-a]pyridine (9)

N

N

S OO

White (79.0 mg, 88%). mp. 151.6-152.3 oC. 1H NMR (400 MHz, CDCl3): δ 9.10 (dd, J1 = 6.97 Hz, J2 = 0.98 Hz, 1H), 7.82-7.77 (m, 2H), 7.65 (dd, J1 = 7.21 Hz, J2 = 0.98 Hz, 1H), 7.63-7.58 (m, 2H), 7.52-7.43 (m, 5H), 7.37-7.31 (m, 3H), 7.12 (d, J = 8.07 Hz, 2H), 7.04 (t, J = 7.09 Hz, 1H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 153.0, 146.2, 144.5, 138.8, 132.5, 132.1, 131.9, 130.9, 129.7, 129.4, 129.1, 128.3, 127.7, 126.4, 122.4, 118.6, 114.3, 114.1, 96.9, 83.4, 21.6. HRMS (ESI) calcd. for C28H20N2O2S (M+H)+: 449.1318, found: 449.1323.

References:

(1) (a) Y. Yu, Y. Yuan, H. Liu, M. He, M. Yang, P. Liu, B. Yu, X. Dong and A. Lei, Chem. Commun., 2019, 55, 1809; (b) S. Takizawa, J. Nishida, T. Tsuzuki, S. Tokito and Y. Yamashita, Inorg. Chem., 2007, 46, 4308.(2) (a) M. Jiang, Y. Yuan, T. Wang, Y. Xiong, J. Li, H. Guo and A. Lei, Chem. Commun., 2019, 55, 13852; (b) W. Kim, H.Y. Kim and K. Oh, Org. Lett., 2020, 22, 6319.(3) (a) A Guide to Recording Fluorescence Quantum Yields-Application Note 1996 (Middlesex: Jobin Yvon). (b) Y. Wei, N. Li and S. Qin, Spectrosc. Spect. Anal., 2004, 24, 647.(4) Y. Zhao and D. G. Truhlar, Theor. Chem. Acc., 2008, 120, 215.(5) (a) F. Weigend and R. Ahlrichs, Phys. Chem. Chem. Phys. 2005, 7, 3297; (b) J. Zheng, X. Xu and D. G. Truhlar, Theor. Chem. Accounts, 2011, 128, 295.(6) Gaussian 16, Revision C.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. V. Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. J. Heyd, E. N. Brothers, K. N. Kudin, V. N. Staroverov, T. A. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam, M. Klene, C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O. Farkas, J. B. Foresman and D. J. Fox, Gaussian, Inc., Wallingford CT, 2019.(7) M. Cossi, V. Barone, R. Cammi and J. Tomasi, Chem. Phys. Lett., 1996, 255, 327.(8) T. Lu and F. Chen, J. Comput. Chem., 2012, 33, 580.(9) W. Humphrey, A. Dalke and K. Schluten, J. Molec. Graphics, 1996, 14, 33.(10) Y.-J. Guo, S. Lu, L.-L. Tian, E.-L. Huang, X.-Q. Hao, X.-J. Zhu, T. Shao, M.-P. Song, J. Org.

S27

Chem., 2018, 83, 338.(11) D. Yang, P. Sun, W. Wei, F. Liu, H. Zhang and H. Wang, Chem. Eur. J., 2018, 24, 4423.(12) C. Breton-Patient, D. Naud-Martin, F. Mahuteau-Betzer and S. Piguel, Eur. J. Org. Chem., 2020, 2020, 6653.(13) D. C. Mohan, M. S. Rao, C. Ravi and S. Adimurthy, Asian J. Org. Chem., 2014, 3, 609.

S28

8. 1H, 13C and 19F NMR Spectra

12820-HLL46-1-1_H.ESP

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 -0.5Chemical Shift (ppm)

3.081.042.034.152.023.051.00

0.00

2.32

7.03

7.03

7.05

7.137.15

7.267.45

7.45

7.46

7.47

7.51

7.53

7.727.

737.

757.

75

9.10

9.12

12820-HLL46-1-1_H.ESP

7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)

1.042.034.152.023.05

7.03

7.03

7.05

7.05

7.06

7.07

7.137.15

7.26

7.427.437.

447.447.45

7.45

7.46

7.47

7.48

7.51

7.53

7.70

7.707.72

7.73

7.75

7.75

3aa

N

N

S OO

Figure S7. 1H NMR spectrum of compound 3aa8901-HLL8-1_C.ESP

176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)

21.5

5

76.7

477

.07

77.3

9

114.

5811

7.77

118.

00

126.

4112

7.80

129.

7013

0.53

132.

67

139.

03

144.

4114

6.59

152.

81

3aa

N

N

S OO

Figure S8. 13C NMR spectrum of compound 3aa

S29

749-HLL97-1_H.ESP


1.002.045.122.003.040.99

0.00

7.05

7.07

7.09

7.26

7.33

7.35

7.47

7.62

7.72

7.74

9.13

9.15

749-HLL97-1_H.ESP


1.002.045.122.003.04

7.05

7.07

7.097.

26

7.33

7.35

7.37

7.47

7.62

7.64

7.72

7.74

3ab

N

N

S OO

Figure S9. 1H NMR spectrum of compound 3ab2021-HLL97-1-1_C.esp


76.7

477.0

677

.38

114.

6811

7.43

118.

03

126.

3412

7.83

129.

0713

0.52

132.

5413

3.37

141.

93

146.

70

153.

12

3ab

N

N

S OO

Figure S10. 13C NMR spectrum of compound 3ab

S30

645-HLL123-1-1_H.ESP

7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7Chemical Shift (ppm)

2.021.014.112.041.042.01

6.77

6.786.

806.

807.01

7.027.

037.

03

7.057.28

7.40

7.417.

437.

437.

447.

457.

457.

467.46

7.55

7.56

7.58

7.59

7.69

7.717.

737.74

7.75

7.76

3ac

N

N

S OO

OCH3

645-HLL123-1-1_H.ESP


3.032.021.014.112.041.042.011.00

0.00

3.75

6.77

6.786.80

7.03

7.287.43

7.43

7.45

7.45

7.467.46

7.56

7.58

7.59

7.74

7.75

7.76

9.09

9.10

Figure S11. 1H NMR spectrum of compound 3ac3751-HLL123-1_C.esp

192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8Chemical Shift (ppm)

55.6

4

76.8

577

.17

77.4

9

114.

2511

4.60

117.

9111

8.20

126.

7612

7.78

128.

6713

0.53

133.

44

146.

43

152.

35163.

47

3ac

N

N

S OO

OCH3

Figure S12. 13C NMR spectrum of compound 3ac

S31

837-HLL132_H.ESP

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 -0.5 -1.0Chemical Shift (ppm)

9.091.012.004.082.053.071.00

0.00

1.25

7.06

7.087.

347.36

7.457.

467.

477.

567.

587.

717.727.73

7.74

9.12

9.14

837-HLL132_H.ESP


1.012.004.082.053.07

7.04

7.047.06

7.06

7.08

7.08

7.27

7.347.36

7.43

7.44

7.44

7.45

7.457.

467.

47

7.56

7.58

7.717.727.

737.

747.

75 3ad

N

N

S OO

Figure S13. 1H NMR spectrum of compound 3ad859-HLL132_C.esp

176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8Chemical Shift (ppm)

30.9

5

35.1

5

76.7

477.0

677

.38

114.

5711

7.87

117.

96

126.

0812

6.29

127.

7712

9.29

130.

5213

2.66

138.

88

146.

56

152.

73

157.

32

3ad

N

N

S OO

Figure S14 13C NMR spectrum of compound 3ad

S32

571-HLL100-1-1_H.esp


2.021.044.102.033.061.00

0.00

6.96

6.97

6.99

7.01

7.08

7.09

7.44

7.45

7.47

7.61

7.70

7.72

7.73

7.749.13

9.15

571-HLL100-1-1_H.esp

7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9Chemical Shift (ppm)

2.021.044.102.033.06

6.96

6.97

6.99

7.01

7.06

7.08

7.09

7.27

7.437.

447.

457.

477.

48

7.49

7.49

7.59

7.597.61

7.62

7.63

7.64

7.70

7.71

7.72

7.73

7.74

3ae

N

N

S OO

F

Figure S15. 1H NMR spectrum of compound 3ae2032-HLL100-1_C.esp


76.7

677

.07

77.3

9

114.

81116.

1911

6.42

118.

12

126.

8212

7.9013

0.50

132.

4413

7.98

138.

01146.

72

153.

10

164.

1616

6.71

3ae

N

N

S OO

F

Figure S16. 13C NMR spectrum of compound 3ae

S33

2031-HLL100-1_F.esp

-45 -50 -55 -60 -65 -70 -75 -80 -85 -90 -95 -100 -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155Chemical Shift (ppm)

-103

.67 3ae

N

N

S OO

F

Figure S17. 19F NMR spectrum of compound 3ae669-HLL179-1-1_H.esp


1.051.996.303.161.00

0.00

7.07

7.09

7.11

7.26

7.28

7.30

7.48

7.51

7.53

7.72

7.759.13

9.14

669-HLL179-1-1_H.esp


1.051.996.303.16

7.077.

097.

117.26

7.287.

30

7.48

7.51

7.53

7.70

7.72

7.75

3af

N

N

S OO

Cl

Figure S18. 1H NMR spectrum of compound 3af

S34

637-HLL179-1-1_C.esp


76.7

377

.05

77.3

6

114.

8811

7.18

118.

13

126.

8212

7.78

127.

9112

9.33

130.

5213

2.35

140.

0014

0.42

146.

78

153.

29

3af

N

N

S OO

Cl

Figure S19. 13C NMR spectrum of compound 3af966-HLL140-3_H.esp


1.004.052.005.010.99

0.00

7.08

7.10

7.12

7.45

7.46

7.48

7.57

7.70

7.72

7.72

7.72

7.73

7.759.

169.

17

966-HLL140-3_H.esp


1.004.052.005.01

7.08

7.10

7.12

7.27

7.447.45

7.45

7.46

7.48

7.49

7.50

7.51

7.57

7.597.70

7.707.72

7.72

7.72

7.73

7.75

3ag

N

N

S OO

CF3

Figure S20. 1H NMR spectrum of compound 3ag

S35

185-HLL140-1-1_C.esp


76.7

2

77.3

6

115.

0211

6.59

118.

2512

1.64

124.

3612

6.16

126.

2012

6.83

127.

9613

0.51

132.

2613

4.71

135.

04

145.

36147.

05

153.

893ag

N

N

S OO

CF3

Figure S21. 13C NMR spectrum of compound 3ag

184-HLL140-1-1_F.esp

8 0 -8 -16 -24 -32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136Chemical Shift (ppm)

-63.

28

3ag

N

N

S OO

CF3

Figure S22. 19F NMR spectrum of compound 3ag

S36

438-HLL172-1_H.ESP


1.001.026.103.081.00

0.00

6.946.

956.

967.

097.

097.

277.

477.

487.

487.

507.

517.77

7.777.

787.

79

9.07

9.08

438-HLL172-1_H.ESP


1.001.026.103.08

6.946.

956.

956.

96

7.07

7.07

7.09

7.09

7.11

7.11

7.27

7.47

7.48

7.48

7.50

7.51

7.517.73

7.757.

767.77

7.777.

787.

79

3ai

N

N

S OO

S

Figure S23. 1H NMR spectrum of compound 3ai458-HLL172-1_C.esp


76.7

777

.09

77.4

1

114.

7811

7.84

118.

06

126.

9412

7.60

127.

8512

9.44

130.

4813

2.27

133.

19

143.

4014

6.73

152.

89

3ai

N

N

S OO

S

Figure S24. 13C NMR spectrum of compound 3ai

S37

891-HLL178_H.esp


1.041.024.254.201.021.001.02

0.000.00

7.09

7.10

7.117.11

7.24

7.45

7.46

7.487.

487.

507.

527.

707.

727.

767.

777.

79

8.668.66

8.67

8.84

9.17

9.189.19

9.19

891-HLL178_H.esp


1.041.024.254.20

7.09

7.107.

117.11

7.11

7.12

7.13

7.137.237.247.

247.

267.

267.

267.

28

7.45

7.46

7.487.

487.

507.

527.

53

7.70

7.72

7.737.

767.

777.

797.

79

3aj

N

N

S OO

N

Figure S25. 1H NMR spectrum of compound 3aj904-HLL178_C.esp


76.7

877

.10

77.4

1

115.

0911

6.84

118.

22

123.

5512

6.83

127.

9913

0.48

132.

1813

3.94

138.

53

146.

9914

7.26

153.

77

3aj

N

N

S OO

N

Figure S26. 13C NMR spectrum of compound 3aj

S38

616-HLL104-1-1_H.ESP


3.101.034.131.012.021.00

0.00

3.03

7.067.

087.

097.27

7.487.

487.

507.

777.

797.

877.

887.

89

9.10

9.12

616-HLL104-1-1_H.ESP


1.034.131.012.02

7.06

7.08

7.097.

27

7.487.

487.

507.

527.77

7.79

7.87

7.88

7.89 3ak

N

N

S OO

CH3

Figure S27. 1H NMR spectrum of compound 3ak2611-HLL104-1-1_C.esp


44.9

9

76.7

677

.08

77.3

9

114.

6711

7.03

118.

03

127.

1012

8.25

130.

2513

2.36

146.

51

151.

93

3ak

N

N

S OO

CH3

Figure S28. 13C NMR spectrum of compound 3ak

S39

617-HLL107-1-1_H.ESP


3.023.062.011.053.032.041.042.020.99

0.00

2.33

2.42

7.137.15

7.42

7.43

7.44

7.45

7.45

7.51

7.53

7.717.

727.

728.89

617-HLL107-1-1_H.ESP

7.75 7.70 7.65 7.60 7.55 7.50 7.45 7.40 7.35 7.30 7.25 7.20 7.15 7.10Chemical Shift (ppm)

2.011.053.032.041.042.02

7.137.

15

7.26

7.28

7.287.30

7.31

7.42

7.43

7.43

7.44

7.45

7.45

7.51

7.53

7.60

7.62

7.70

7.71

7.717.

727.

72

3ba

N

N

S OO

Figure S29. 1H NMR spectrum of compound 3ba638-HLL107-1-1_C.esp


18.6

221

.52

76.7

477

.05

77.3

7

117.

1811

7.32

124.

5712

6.36

127.

7312

9.6413

0.49

131.

4613

2.82

139.

22

144.

2714

5.60

152.

60

3ba

N

N

S OO

Figure S30. 13C NMR spectrum of compound 3ba

S40

606-HLL134-1-3_H.ESP


3.003.012.021.063.082.041.082.070.99

0.00

2.333.

91

7.137.

147.

237.

277.

447.

457.

507.

527.

577.71

7.72

8.68

606-HLL134-1-3_H.ESP

7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)

2.021.063.082.041.082.07

7.137.

14

7.207.207.22

7.23

7.27

7.44

7.45

7.50

7.52

7.57

7.60

7.71

7.72

3ca

N

N

S OO

MeO

Figure S31. 1H NMR spectrum of compound 3ca636-HLL134-1-3_C.esp


21.5

3

56.3

9

76.7

477.0

677

.38

108.

91

117.

9011

8.19

123.

2312

6.40

127.

75129.

6313

0.46

132.

85

139.

04

143.

43144.

36

150.

4115

2.43

3ca

N

N

S OO

MeO

Figure S32. 13C NMR spectrum of compound 3ca

S41

647-HLL113-1-1_H.ESP


3.012.011.043.072.073.081.00

0.00

2.32

7.137.

157.

367.

367.

457.

467.

497.

527.

677.

717.

717.73

7.73

9.12

9.13

9.13

9.14

647-HLL113-1-1_H.ESP


2.011.043.072.073.08

7.137.

15

7.277.33

7.34

7.35

7.36

7.36

7.38

7.427.

437.

447.

457.

467.46

7.47

7.49

7.52

7.66

7.67

7.68

7.70

7.71

7.717.

737.

73

3da

N

N

S OO

F

Figure S33. 1H NMR spectrum of compound 3da3161-HLL113-1_C.esp


21.5

6

76.7

677

.08

77.3

9

114.

0811

4.51

118.

3311

8.41

120.

1412

0.39

126.

4512

7.87

129.

7713

0.42

132.

39

138.

72

144.

06144.

71

152.

7615

3.34

155.

15

3da

N

N

S OO

F

Figure S34. 13C NMR spectrum of compound 3da

S42

3162-HLL113-1_F.esp

-65 -70 -75 -80 -85 -90 -95 -100 -105 -110 -115 -120 -125 -130 -135 -140 -145 -150 -155 -160 -165 -170 -175 -180 -185 -190 -195 -200Chemical Shift (ppm)

-135

.38 3da

N

N

S OO

F

Figure S35. 19F NMR spectrum of compound 3da769-HLL114_H.ESP


2.992.016.231.022.000.99

0.00

2.34

7.147.

167.

437.45

7.47

7.49

7.51

7.647.

697.

707.

71

9.22

769-HLL114_H.ESP

7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)

2.016.231.022.00

7.147.

16

7.26

7.407.41

7.437.

437.45

7.47

7.49

7.51

7.64

7.66

7.69

7.70

7.71

7.72

3ea

N

N

S OO

Cl

Figure S36. 1H NMR spectrum of compound 3ea

S43

784-HLL114_C.esp


21.5

6

76.7

277

.04

77.3

6

118.

2211

8.5912

2.9312

4.84

126.

4812

7.8812

9.77

130.

4513

2.24

138.

74

144.

7114

4.82

153.

10

3ea

N

N

S OO

Cl

Figure S37. 13C NMR spectrum of compound 3ea747-HLL142_H.ESP


3.012.016.121.022.020.99

0.00

2.33

7.147.16

7.26

7.43

7.45

7.46

7.48

7.50

7.597.

707.

71

9.31

747-HLL142_H.ESP


2.016.121.022.02

7.147.

16

7.26

7.43

7.45

7.46

7.48

7.50

7.52

7.52

7.59

7.61

7.69

7.70

7.71

3fa

N

N

S OO

Br

Figure S38. 1H NMR spectrum of compound 3fa

S44

793-HLL142_C.esp


21.5

6

76.7

477

.06

77.3

8

109.

43

118.

4511

8.49

126.

4812

7.8712

9.77

130.

4513

1.92

132.

22

138.

73144.

7214

4.92

152.

93

3fa

N

N

S OO

Br

Figure S39. 13C NMR spectrum of compound 3fa746-HLL121_H.esp

10.0 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 -0.5Chemical Shift (ppm)

3.122.075.221.092.081.091.00

0.00

2.33

7.147.

167.

267.

457.

467.

487.

517.

617.

727.

747.

807.

82

9.55

746-HLL121_H.esp

7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)

2.075.221.092.081.09

7.147.16

7.26

7.45

7.46

7.48

7.51

7.587.617.

727.72

7.74

7.80

7.82

3ga

N

N

S OO

F3C

Figure S40. 1H NMR spectrum of compound 3ga

S45

798-HLL121_C.esp


21.5

5

76.7

3

77.3

6

118.

7011

9.6212

4.31

126.

0112

6.60

127.

9512

9.81

130.

4913

1.93

138.

42

144.

9814

6.24

153.

94

3ga

N

N

S OO

F3C

Figure S41. 13C NMR spectrum of compound 3ga10-HLL121-1-1_F.esp

5 0 -5 -10 -15 -20 -25 -30 -35 -40 -45 -50 -55 -60 -65 -70 -75 -80 -85 -90 -95 -100 -105 -110 -115 -120 -125 -130Chemical Shift (ppm)

-62.

01

3ga

N

N

S OO

F3C

Figure S42. 19F NMR spectrum of compound 3ga

S46

570-HLL120-1-1_H.esp


3.073.100.982.004.031.972.031.00

0.00

2.31

2.44

6.866.86

6.88

7.117.

137.

277.43

7.447.

457.

457.46

7.50

7.52

7.737.75

7.75

8.95

8.97

570-HLL120-1-1_H.esp


0.982.004.031.972.03

6.86

6.86

6.88

6.88

7.117.13

7.27

7.43

7.43

7.447.

457.

457.46

7.50

7.52

7.73

7.737.

747.747.75

7.75

3ha

N

N

S OO

Figure S43. 1H NMR spectrum of compound 3ha592-HLL120-1-1_C.esp


21.3

521

.50

76.7

777

.09

77.4

1

116.

4511

7.14

125.

9212

6.3212

7.75

129.

6613

0.52

132.

74

139.

24140.

09

144.

2314

7.04

152.

87

3ha

N

N

S OO

Figure S44. 13C NMR spectrum of compound 3ha

S47

839-HLL153_H.esp


3.023.021.000.992.005.082.001.00

0.00

2.313.

86

6.71

6.726.73

6.95

6.967.

127.14

7.277.43

7.447.45

7.46

7.49

7.51

7.75

7.76

7.77

8.89

8.90

839-HLL153_H.esp

7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6Chemical Shift (ppm)

1.000.992.005.082.00

6.706.71

6.726.73

6.95

6.967.

127.14

7.277.43

7.447.

457.

457.

457.46

7.49

7.51

7.74

7.74

7.75

7.76

7.77

3ia

N

N

S OO

MeO

Figure S45. 1H NMR spectrum of compound 3ia861-HLL153_C.esp


21.4

9

55.8

0

76.7

777

.09

77.4

1

95.4

5

109.

06

116.

52

126.

2412

7.74

129.

6613

0.46

132.

70139.

37

144.

16

148.

69

153.

18160.

39

3ia

N

N

S OO

MeO

Figure S46. 13C NMR spectrum of compound 3ia

S48

745-HLL165_H.esp


3.031.042.045.123.141.00

0.00

2.32

7.027.02

7.04

7.04

7.127.

147.

267.

457.

477.

477.

497.

697.

717.

73

9.06

9.07

745-HLL165_H.esp


1.042.045.123.14

7.02

7.02

7.04

7.04

7.127.14

7.26

7.45

7.47

7.47

7.49

7.69

7.71

7.71

7.73

3ja

N

N

S OO

Cl

Figure S47. 1H NMR spectrum of compound 3ja792-HLL165_C.esp


21.5

4

76.7

677

.08

77.3

9

116.

0911

6.87

118.

28

126.

4212

7.88

129.

7613

0.48

132.

20

135.

36

138.

78144.

6614

6.45

153.

44

3ja

N

N

S OO

Cl

Figure S48. 13C NMR spectrum of compound 3ja

S49

712-HLL169_H.esp


3.043.061.032.040.983.062.072.071.00

0.00

2.32

2.63

6.93

6.95

6.96

7.127.

147.

227.

247.

457.

467.

467.

517.

53

7.72

7.73

7.73

8.95

8.96

712-HLL169_H.esp


1.032.040.983.062.072.07

6.93

6.95

6.96

7.127.

14

7.22

7.24

7.26

7.45

7.46

7.46

7.51

7.53

7.717.

727.

737.

73

3ka

N

N

S OO

Figure S49. 1H NMR spectrum of compound 3ka741-HLL169-1_C.esp


17.1

0

21.5

2

76.7

477

.06

77.3

8

114.

56

118.

10

124.

4612

6.43

127.

2612

9.6413

0.61

132.

97

139.

18

144.

2514

6.84

152.

25

3ka

N

N

S OO

Figure S50. 13C NMR spectrum of compound 3ka

S50

525-HLL171-1-2_H.esp


3.041.002.026.332.071.00

0.00

2.33

6.98

7.00

7.127.

147.

267.

447.

467.

487.

507.

517.

717.

73

9.09

9.10

525-HLL171-1-2_H.esp


1.002.026.332.07

6.98

7.00

7.02

7.127.

14

7.26

7.44

7.46

7.48

7.50

7.51

7.53

7.71

7.73

3la

N

N

S OO

Cl

Figure S51. 1H NMR spectrum of compound 3la339-H171-1-1_C.esp


21.5

4

76.7

477

.05

77.3

7

114.

15

119.

75123.

8712

5.49

126.

5212

7.7812

9.74

130.

7013

2.21

138.

65

143.

92144.

72

152.

92

3la

N

N

S OO

Cl

Figure S52. 13C NMR spectrum of compound 3la

S51

925-HLL173_H.esp


3.051.022.035.103.001.00

0.00

2.32

6.91

6.93

6.95

7.127.

147.

267.

427.

447.

467.

477.

497.

687.

717.

737.

73

9.12

9.14

925-HLL173_H.esp


1.022.035.103.00

6.916.

936.

95

7.127.14

7.26

7.42

7.43

7.44

7.46

7.47

7.49

7.687.68

7.69

7.71

7.73

7.73

3ma

N

N

S OO

Br

Figure S53. 1H NMR spectrum of compound 3ma934-HLL173_C.esp


21.5

5

76.7

677

.07

77.3

9

112.

0011

4.54

119.

80

126.

0612

6.51

127.

78129.

7413

0.73

132.

26

138.

68

144.

41144.

71

152.

94

3ma

N

N

S OO

Br

Figure S54. 13C NMR spectrum of compound 3ma

S52

4440-HLL126-1_H.ESP


3.053.051.022.002.131.062.022.011.081.01

0.00

2.33

2.44

7.03

7.03

7.147.16

7.26

7.267.

287.

437.

537.

557.65

7.67

7.69

7.71

7.719.

079.

079.

089.09

4440-HLL126-1_H.ESP


1.022.002.131.062.022.011.08

7.01

7.01

7.03

7.03

7.04

7.05

7.147.

16

7.26

7.267.

28

7.41

7.41

7.437.437.43

7.43

7.45

7.45

7.53

7.557.

657.

677.

697.

697.71

7.71

3na

N

N

S OO

Figure S55. 1H NMR spectrum of compound 3na15-HLL126-1_C.esp


21.5

2

76.7

477.0

677

.37

114.

5011

7.55

117.

86

126.

3812

8.54

129.

6913

0.45

139.

1113

9.37

144.

3614

6.54

152.

92

3na

N

N

S OO

Figure S56. 13C NMR spectrum of compound 3na

S53

758-HLL161_H.esp


3.093.123.152.081.062.031.062.021.00

0.00

2.32

3.89

6.987.

00

7.137.15

7.277.43

7.52

7.54

7.68

7.73

7.76

9.08

9.10

758-HLL161_H.esp


3.152.081.062.031.062.02

6.987.

007.

037.

04

7.137.

15

7.27

7.417.

437.

45

7.52

7.54

7.68

7.71

7.73

7.76

3oa

N

N

S OO

OCH3

Figure S57. 1H NMR spectrum of compound 3oa788-HLL161_C.esp


21.5

2

55.3

4

76.7

477

.06

77.3

7

113.

3111

4.42

117.

2311

7.78

124.

9012

6.31

128.

4812

9.69

132.

03

139.

15

144.

3314

6.57

152.

70160.

64

3oa

N

N

S OO

OCH3

Figure S58. 13C NMR spectrum of compound 3oa

S54

452-HLL174-1_H.esp


3.051.064.111.042.001.012.001.00

0.00

2.33

7.047.

067.13

7.15

7.17

7.18

7.26

7.46

7.51

7.53

7.747.76

7.77

7.78

9.09

9.11

452-HLL174-1_H.esp


1.064.111.042.001.012.00

7.04

7.04

7.06

7.06

7.08

7.13

7.15

7.15

7.17

7.18

7.26

7.44

7.44

7.457.

467.

467.

487.

487.

517.

53

7.69

7.727.

747.76

7.77

7.78

3pa

N

N

S OO

F

Figure S59. 1H NMR spectrum of compound 3pa475-HLL174-1_C.esp


21.5

3

76.7

277

.03

77.3

6

114.

6711

4.79

115.

0111

7.77

117.

95

126.

3312

6.83

128.

6912

9.76

132.

58

138.

97144.

5414

6.56

151.

70

162.

3816

4.85

3pa

N

N

S OO

F

Figure S60. 13C NMR spectrum of compound 3pa

S55

488-HLL174-1_F.esp

-32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176 -184 -192Chemical Shift (ppm)

-111

.86 3pa

N

N

S OO

F

Figure S61. 19F NMR spectrum of compound 3pa713-HLL162_H.esp


3.101.012.033.112.073.131.00

0.00

2.34

7.05

7.06

7.167.

187.

267.

437.

457.

527.

547.

707.

717.

73

9.08

9.10

713-HLL162_H.esp


1.012.033.112.073.13

7.05

7.06

7.08

7.167.

18

7.26

7.43

7.45

7.48

7.52

7.54

7.70

7.71

7.73

3qa

N

N

S OO

Cl

Figure S62. 1H NMR spectrum of compound 3qa

S56

740-HLL162_C.esp


21.5

4

76.7

177

.03

77.3

5

114.

7411

7.9111

8.02

126.

3512

8.09

129.

8113

1.93

135.

63

138.

90

144.

6214

6.62

151.

45

3qa

N

N

S OO

Cl

Figure S63. 13C NMR spectrum of compound 3qa982-HLL163-1_H.ESP


3.001.022.001.062.013.022.021.00

0.00

2.34

7.077.

097.

097.

167.18

7.277.48

7.53

7.55

7.717.

737.

747.

887.

90

9.08

9.09

982-HLL163-1_H.ESP


1.022.001.062.013.022.02

7.07

7.07

7.09

7.09

7.10

7.11

7.167.

18

7.27

7.46

7.46

7.487.

487.

487.

507.

507.

537.

55

7.71

7.72

7.72

7.73

7.74

7.88

7.90

3ra

N

N

S OO

CF3

Figure S64. 1H NMR spectrum of compound 3ra

S57

920-HLL163_C.ESP


21.5

1

76.7

377

.04

77.3

6

114.

94118.

1411

8.34

122.

7812

4.70

124.

7312

6.41

128.

7712

9.85

130.

9813

1.33

136.

33138.

70144.

7714

6.67

150.

93

3ra

N

N

S OO

CF3

Figure S65. 13C NMR spectrum of compound 3ra796-HLL163_F.esp

8 0 -8 -16 -24 -32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136Chemical Shift (ppm)

-62.

64

3ra

N

N

S OO

CF3

Figure S66. 19F NMR spectrum of compound 3ra

S58

7220-HLL186_H.ESP


2.991.022.021.201.972.971.994.023.000.99

9.00

8.99

7.88 7.

837.

82 7.81

7.62

7.59 7.

57 7.49

7.49

7.48

7.48 7.35

7.27

7.14

7.12

7.05

7.03

2.31

0.00

7

N

N

S OO

7220-HLL186_H.ESP


1.022.021.201.972.971.994.023.00

7.88

7.83

7.82 7.

82 7.81

7.80 7.

627.

597.

57

7.54 7.

527.

507.

497.

497.

487.

487.

47

7.37

7.35

7.33

7.29 7.

277.

25

7.14

7.12

7.06

7.05

7.03

Figure S67. 1H NMR spectrum of compound 7

6581-HLL186_C.ESP


21.5

6

76.7

677.0

777

.39

114.

75

118.

0612

2.26

124.

3612

4.94

126.

4412

7.16

128.

6912

9.71

130.

8113

2.88

134.

1713

6.92

139.

03

144.

3814

5.20

152.

39

7

N

N

S OO

Figure S68. 13C NMR spectrum of compound 7

S59

7370-HLL187_H.esp

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 -0.5 -1.0Chemical Shift (ppm)

3.001.012.023.005.062.001.012.001.00

0.00

2.31

7.02

7.047.

117.13

7.337.33

7.347.

357.

467.

487.

507.

597.60

7.61

7.79

7.81

9.099.09

9.11

7370-HLL187_H.esp


1.012.023.005.062.001.012.00

7.02

7.04

7.06

7.117.

13

7.25

7.337.33

7.347.

35

7.45

7.45

7.46

7.46

7.48

7.50

7.597.

607.

617.

617.

647.64

7.66

7.79

7.81

7.81

9

N

N

S OO

Figure S69. 1H NMR spectrum of compound 97371-HLL187_C.ESP


21.5

6

76.7

777

.09

77.4

183

.45

96.9

3114.

1211

4.32

118.

63122.

42

126.

4312

8.34

129.

7213

1.94

132.

0713

2.48

138.

84

144.

5514

6.24

153.

05

9

N

N

S OO

Figure S70. 13C NMR spectrum of compound 9

S60

9. X-Ray Crystallographic Data

The structure of 3aa, 3ad, 3ca, 3da and 3na were determined by the X-ray diffraction. Recrystallized from dichloromethane. Further information can be found in the CIF file. These crystals were deposited in the Cambridge Crystallographic Data Centre and assigned as CCDC 2003750 (3aa), 2046849 (3ad), 2046836 (3ca), 2046840 (3da) and 2046841 (3na).

Figure S71. X-ray structure of compound 3aa (CCDC 2003750)

Table S2. Crystal data and structure refinement for 3aa.

Identification code 201912329Empirical formula C20H16N2O2SFormula weight 348.41Temperature/K 293(2)Crystal system triclinicSpace group P-1

a/Å 9.2243(9)b/Å 9.2775(13)c/Å 11.9174(11)α/° 109.972(11)β/° 100.537(9)γ/° 108.093(11)

S61

Volume/Å3 862.17(19)Z 2

ρcalcg/cm3 1.342μ/mm-1 1.794F(000) 364.0

Crystal size/mm3 0.15 × 0.1 × 0.08Radiation CuKα (λ = 1.54184)

2Θ range for data collection/°

8.342 to 141.842

Index ranges -11 ≤ h ≤ 10, -11 ≤ k ≤ 11, -9 ≤ l ≤ 14Reflections collected 6330

Independent reflections 3249 [Rint = 0.0318, Rsigma = 0.0509]Data/restraints/parameters 3249/0/228

Goodness-of-fit on F2 1.035Final R indexes [I > = 2σ (I)] R1 = 0.0487, wR2 = 0.1260

Final R indexes [all data] R1 = 0.0651, wR2 = 0.1408Largest diff. peak/hole / e Å-3 0.28/-0.29

Figure S72. X-ray structure of compound 3ad (CCDC 2046849)

Table S3. Crystal data and structure refinement for 3ad.

Identification code 202007110

S62

Empirical formula C23H22N2O2SFormula weight 390.48Temperature/K 293(2)Crystal system monoclinicSpace group P21/c

a/Å 17.5438(7)b/Å 18.4815(6)c/Å 13.4134(4)α/° 90

β/° 107.063(4)γ/° 90

Volume/Å3 4157.6(3)Z 8

ρcalcg/cm3 1.248μ/mm-1 1.541F(000) 1648.0



7.118 to 134.152


Independent reflections 7412 [Rint = 0.0364, Rsigma = 0.0460]Data/restraints/parameters 7412/108/536

Goodness-of-fit on F2 1.027Final R indexes [I > = 2σ (I)] R1 = 0.0541, wR2 = 0.1396

Final R indexes [all data] R1 = 0.0827, wR2 = 0.1675Largest diff. peak/hole / e Å-3 0.50/-0.31

S63

Figure S73. X-ray structure of compound 3ca (CCDC 2046836)

Table S4. Crystal data and structure refinement for 3ca.

Identification code 202007107Empirical formula C21H18N2O3SFormula weight 378.43Temperature/K 293(2)Crystal system monoclinicSpace group P21/c

a/Å 8.29236(19)b/Å 14.5610(4)c/Å 15.4305(3)α/° 90β/° 91.003(2)γ/° 90

Volume/Å3 1862.87(8)Z 4

ρcalcg/cm3 1.349μ/mm-1 1.745F(000) 792.0


S64


8.35 to 134.156


Independent reflections 3322 [Rint = 0.0283, Rsigma = 0.0393]

Data/restraints/parameters 3322/0/248Goodness-of-fit on F2 1.036

Final R indexes [I > = 2σ (I)] R1 = 0.0458, wR2 = 0.1209Final R indexes [all data] R1 = 0.0580, wR2 = 0.1319

Largest diff. peak/hole / e Å-3 0.32/-0.29

Figure S74. X-ray structure of compound 3da (CCDC 2046840)

Table S5. Crystal data and structure refinement for 3da.

Identification code 202007108Empirical formula C20H15FN2O2SFormula weight 366.40Temperature/K 293(2)Crystal system monoclinicSpace group P21/c

a/Å 13.7672(3)

S65

b/Å 12.5717(3)c/Å 10.2914(3)α/° 90β/° 100.758(2)γ/° 90

Volume/Å3 1749.90(7)Z 4

ρcalcg/cm3 1.391μ/mm-1 1.881F(000) 760.0


2Θ range for data collection/° 9.604 to 134.126Index ranges -9 ≤ h ≤ 16, -12 ≤ k ≤ 15, -12 ≤ l ≤ 12

Reflections collected 6568Independent reflections 3126 [Rint = 0.0284, Rsigma = 0.0351]




S66

Figure S75. X-ray structure of compound 3na (CCDC 2046841)

Table S6. Crystal data and structure refinement for 3na.

Identification code 202007109Empirical formula C21H18N2O2SFormula weight 362.43Temperature/K 293(2)Crystal system monoclinicSpace group P21/n

a/Å 9.3338(3)b/Å 15.3970(4)c/Å 12.9510(3)α/° 90β/° 93.887(3)γ/° 90

Volume/Å3 1856.95(8)Z 4

ρcalcg/cm3 1.296μ/mm-1 1.685F(000) 760.0


2Θ range for data collection/° 8.934 to 134.132Index ranges -11 ≤ h ≤ 9, -18 ≤ k ≤ 16, -15 ≤ l ≤ 15

Reflections collected 6984Independent reflections 3308 [Rint = 0.0310, Rsigma = 0.0404]




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