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1 Type of file: PDF Size of file: 0 KB Title of file for HTML: Supplementary Information Description: Supplementary figures, supplementary tables, supplementary discussion, supplementary methods and supplementary references. Type of file: PDF Size of file: 0 KB Title of file for HTML: Peer review file Description:

2 Supplementary Figures Supplementary Figure 1. 1 H and 13 C NMR spectra for compound 1l S-1

3 Supplementary Figure 2. 1 H and 13 C NMR spectra for compound 3aa S-2

4 Supplementary Figure 3. 1 H and 13 C NMR spectra for compound 3ba S-3

5 Supplementary Figure 4. 1 H and 13 C NMR spectra for compound 3ca S-4

6 Supplementary Figure 5. 1 H and 13 C NMR spectra for compound 3da S-5

7 Supplementary Figure 6. 1 H and 13 C NMR spectra for compound 3ea S-6

8 Supplementary Figure 7. 1 H and 13 C NMR spectra for compound 3fa S-7

9 Supplementary Figure 8. 1 H and 13 C NMR spectra for compound 3ga S-8

10 Supplementary Figure 9. 1 H and 13 C NMR spectra for compound 3ha S-9

11 Supplementary Figure H and 13 C NMR spectra for compound 3ia S-10

12 Supplementary Figure H and 13 C NMR spectra for compound 3ja S-11

13 Supplementary Figure H and 13 C NMR spectra for compound 3ja S-12

14 Supplementary Figure H and 13 C NMR spectra for compound 3ka S-13

15 Supplementary Figure H and 13 C NMR spectra for compound 3ka S-14

16 Supplementary Figure H and 13 C NMR spectra for compound 3la S-15

17 Supplementary Figure H and 13 C NMR spectra for compound 3ma S-16

18 Supplementary Figure H and 13 C NMR spectra for compound 3ma S-17

19 Supplementary Figure H and 13 C NMR spectra for compound 3na S-18

20 Supplementary Figure H and 13 C NMR spectra for compound 3na S-19

21 Supplementary Figure H and 13 C NMR spectra for compound 3oa S-20

22 Supplementary Figure H, 19 F and 13 C NMR spectra for compound 3ab S-21

23 Supplementary Figure H and 13 C NMR spectra for compound 3ac S-22

24 Supplementary Figure H and 13 C NMR spectra for compound 3ad S-23

25 Supplementary Figure H and 13 C NMR spectra for compound 3ae S-24

26 Supplementary Figure H and 13 C NMR spectra for compound 3af S-25

27 Supplementary Figure H and 13 C NMR spectra for compound 3ag S-26

28 Supplementary Figure H and 13 C NMR spectra for compound 3ah S-27

29 Supplementary Figure H and 13 C NMR spectra for compound 3ai S-28

30 Supplementary Figure H and 13 C NMR spectra for compound 3aj S-29

31 Supplementary Figure H and 13 C NMR spectra for compound 3pa S-30

32 Supplementary Figure H, 31 P NMR and 13 C NMR spectra for compound 1q S-31

33 Supplementary Figure H NMR and 13 C NMR spectra for compound 1a-d 8 S-32

34 Supplementary Figure 33: X-ray diffraction structure of compound 3aa (CCDC ). S-33

35 Supplementary Figure 34: X-ray diffraction structure of compound 3ab (CCDC ). S-34

36 a b Supplementary Figure 35. The absorption and fluorescence spectra of reaction of 1q and 2k. (a) The absorption spectra of reaction of 1q and 2k in MeOH ( mol L -1 ). The maximum excitation wavelength of 3qk is 362nm; (b) The fluorescence spectra of reaction of 1q and 2k in MeOH ( mol L -1, λ ex = 362 nm). The maximum emission wavelength of 3qk is 450nm. Under the maximum emission wavelength, the fluorescence intensity is increased 107 times in 30 minites. S-35

37 Supplementary Table Supplementary Table 1. Crystal data and structure refinement for 3aa. Identification code Empirical formula 3aa C 10 H 13 NO 2 S Formula weight Temperature/K Crystal system monoclinic Space group P2 1 /c a/å 9.659(13) b/å (18) c/å 8.211(10) α/ 90 β/ (13) γ/ 90 Volume/Å (2) Z 4 ρ calc g/cm μ/mm F(000) Crystal size/mm Radiation Mo Kα (λ = ) 2Θ range for data collection/ 6.7 to 54.9 Index ranges -12 h 11, -17 k 15, -10 l 10 Reflections collected 8159 Independent reflections 2435 [R int = , R sigma = ] Data/restraints/parameters 2435/0/126 Goodness-of-fit on F Final R indexes [I>=2σ (I)] R 1 = , wr 2 = Final R indexes [all data] R 1 = , wr 2 = Largest diff. peak/hole / e Å /-1.35 S-36

38 Supplementary Table 2. Bond Lengths for 3aa. Atom Atom Length/Å Atom Atom Length/Å S1 N (2) C1 C (4) S1 C (3) C2 C (4) S1 C (3) C3 C (4) O1 C (3) C4 C (4) O2 C (3) C5 C (4) N1 C (3) C7 C (3) C1 C (3) C9 C (3) Supplementary Table 3. Bond Angles for 3aa. Atom Atom Atom Angle/ Atom Atom Atom Angle/ C2 S1 N (11) C3 C2 C (2) C7 S1 N (11) C4 C3 C (2) C7 S1 C (11) C5 C4 C (3) C9 N1 S (15) C6 C5 C (3) C2 C1 O (2) C5 C6 C (2) C6 C1 O (2) C8 C7 S (2) C6 C1 C (2) N1 C9 O (2) C1 C2 S (2) C10 C9 O (2) C3 C2 S (17) C10 C9 N (2) Supplementary Table 4. Crystal data and structure refinement for 3ab. Identification code Empirical formula 3ab C 9 H 8 F 3 NO 2 S Formula weight Temperature Wavelength Crystal system Space group 295(2) K Å Orthorhombic P b c a Unit cell dimensions a = (7) Å = 90. b = (2) Å = 90. S-37

39 c = (14) Å = 90. Volume (19) Å 3 Z 8 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 1024 Crystal size 0.20 x 0.05 x 0.05 mm 3 Theta range for data collection 7.03 to Index ranges -16<=h<=16, -9<=k<=8, -23<=l<=21 Reflections collected Independent reflections 1879 [R(int) = ] Completeness to theta = % Absorption correction Semi-empirical from equivalents Max. and min. transmission and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 1879 / 1 / 150 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Largest diff. peak and hole and e.å -3 S-38

40 Supplementary Table 5. Bond lengths [Å] and angles [ ] for 3ab. S(1)-N(1) (19) S(1)-C(2) 1.773(2) S(1)-C(9) 1.867(3) F(1)-C(9) 1.298(3) F(2)-C(9) 1.299(3) F(3)-C(9) 1.302(3) N(1)-C(1) 1.350(3) O(1)-C(1) 1.242(3) O(2)-C(3) 1.349(3) O(2)-HO (18) C(1)-C(6) 1.497(3) C(2)-C(8) 1.382(3) C(2)-C(3) 1.393(3) C(3)-C(4) 1.388(3) C(4)-C(5) 1.375(4) C(4)-H(4) C(5)-C(7) 1.380(4) C(5)-H(5) C(6)-H(6A) C(6)-H(6B) C(6)-H(6C) C(7)-C(8) 1.388(3) C(7)-H(7) C(8)-H(8) N(1)-S(1)-C(2) (10) N(1)-S(1)-C(9) (11) C(2)-S(1)-C(9) 97.44(11) C(1)-N(1)-S(1) (16) C(3)-O(2)-HO2 112(2) O(1)-C(1)-N(1) 125.1(2) O(1)-C(1)-C(6) 121.0(2) N(1)-C(1)-C(6) 113.9(2) C(8)-C(2)-C(3) 121.7(2) C(8)-C(2)-S(1) (17) C(3)-C(2)-S(1) (17) S-39

41 O(2)-C(3)-C(4) 123.3(2) O(2)-C(3)-C(2) 118.3(2) C(4)-C(3)-C(2) 118.4(2) C(5)-C(4)-C(3) 119.9(2) C(5)-C(4)-H(4) C(3)-C(4)-H(4) C(4)-C(5)-C(7) 121.6(2) C(4)-C(5)-H(5) C(7)-C(5)-H(5) C(1)-C(6)-H(6A) C(1)-C(6)-H(6B) H(6A)-C(6)-H(6B) C(1)-C(6)-H(6C) H(6A)-C(6)-H(6C) H(6B)-C(6)-H(6C) C(5)-C(7)-C(8) 119.3(2) C(5)-C(7)-H(7) C(8)-C(7)-H(7) C(2)-C(8)-C(7) 119.1(2) C(2)-C(8)-H(8) C(7)-C(8)-H(8) F(1)-C(9)-F(2) 108.4(2) F(1)-C(9)-F(3) 109.3(2) F(2)-C(9)-F(3) 107.7(2) F(1)-C(9)-S(1) (19) F(2)-C(9)-S(1) (18) F(3)-C(9)-S(1) (19) Symmetry transformations used to generate equivalent atoms: S-40

42 Supplementary Table 6: Condition Screening for C-S bond coupling reaction. Entry Solvent time Additive(eq.) Yield(%) [b] 1 [c] MeOH 15h CsOAc(0.3) 89 [a] 2 [c] 3 MeOH MeOH 15h 15h CsOAc(0.3) CsOAc(0.3) 4 MeOH 1h CsOAc(0.3) MeOH MeOH MeOH i-proh 2h 3h 10h 3h CsOAc(0.3) CsOAc(0.3) CsOAc(0.3) CsOAc(0.3) 9 CH 2 Cl 2 3h CsOAc(0.3) CH 3 CN 3h CsOAc(0.3) t-amoh 3h CsOAc(0.3) THF 3h CsOAc(0.3) DCE 3h CsOAc(0.3) MeOH MeOH 3h 10h CsOAc(0.3) [a] trace 16 MeOH 3h CsOAc(0.5) MeOH 3h CsOAc(1.0) MeOH 3h CsOAc(1.5) MeOH 3h CsOAc(0.5) 92 [a] 20 PBS buffer 10h CsOAc(0.3) DMSO:PBS=1:20 10h CsOAc(0.5) 81 [a] Yields of isolated products. [b] Crude yield, as determined by 1 H NMR spectroscopy using 1,4-Dimethoxybenzene as an internal standard. [c] Under N 2. S-41

43 Supplementary Methods General Commercially available chemicals were obtained from Sigma-Aldrich, Alfa Aesar, TCI and Aladdin and used as received unless otherwise stated. Dichloro(η 5 -pentamethylcyclopentadienyl)rhodium(iii) dimer (99%) was purchased from Sinocompound Technology Co., Ltd. Reactions were monitored with analytical thin-layer chromatography (TLC) on silica. 1 H NMR and 13 C NMR data were recorded on Bruker nuclear resonance (300 MHz, 400 MHz and 500MHz) spectrometers unless otherwise specified, respectively. Chemical shifts (δ) are given in ppm relative to TMS. The residual solvent signals were used as references and the chemical shifts converted to the TMS scale (CDCl 3 : δ H =7.26 ppm, δ C =77.16 ppm; CD 2 Cl 2 : δ H =5.32 ppm, δ C =54.00 ppm; DMSO-d 6 : δ H =2.50 ppm, δ C =39.52 ppm; MeOD-d 4 : δ H =3.31 ppm, δ C =49.00 ppm; Acetone-d 6 : δ H =2.05 ppm, δ C =29.84 ppm, ppm). HRMS (ESI) analysis was performed by The Analytical Instrumentation Center at Peking University, Shenzhen Graduate School and (HRMS) data were reported with ion mass/charge (m/z) ratios as values in atomic mass units. Preparation of starting materials 1) Synthesis of 1a-1k, 1m-1o General procedure: Following a literature report 1, in a 50mL round-bottom flask, S-42

44 N-hydroxyphthalimide (1.0 eq.), cooper (I) chloride (1.0 eq.), freshly activated 4 Å molecular sieves (250mg/mmol), and phenylboronic acid (2.0 eq.) were combined in 1,2-dichloroethane(0.2 M). The pyridine (1.1 eq.) was then added to the suspension. The reaction mixture was open to the atmosphere and stirred at room temperature over 24-48h.Upon completion, silica gel was added to the flask and the solvent was removed under vacuum. The desired N-aryloxyphthalimides were obtained by flash column chromatography on silica gel. Hydrazine monohydrate (3.0 eq.) was added to the solution of N-aryloxyphthalimide (1.0eq.) in 10% MeOH in CHCl 3 (0.1 M). The reaction was allowed to stir at room temperature over 12h. Upon completion, the reaction mixture was filtered off and washed with CH 2 Cl 2.The filtrate was concentrated under reduced pressure, and purified by flash silica gel column chromatography to give the corresponding N-aryloxyamine. In a 20 ml round-bottom flask, N-aryloxyamine (1.0 eq.) was dissolved in ether (0.2 M). The flask was cooled in an ice bath, to which acid anhydride (2.0 eq.) was slowly added. The ice bath was allowed to warm to room temperature and the mixture was stirred for 3 h at room temperature. The reaction mixture was concentrated under reduced pressure and purified by flash silica gel column chromatography to give the corresponding N-acetyl aryloxyamine. 2) Synthesis of 2b Following a literature report 2, In a glovebox, a 100 ml round bottom flask with 2-chloroisoindoline-1,3-dione (1.81 g, 10.0 mmol), AgSCF 3 (2.70g, 13.0 mmol) was added 20 ml dried CH 3 CN, the mixture was stirred 3 h at room temperature. Then the solvent was evacuated under rotary evaporator. The residue was added DCM, then filtered through a layer of celite. The filter was evacuated again under reduced pressure. 3) Synthesis of 2a, 2c-2l Following a literature report 3,sulfuryl chloride (1.0 equiv; ca. 5 M in CH 2 Cl 2 ) was added dropwise via a dropping funnel to a solution of thiol (0.05 mol; ca. 1 M in CH 2 Cl 2 ) and Et 3 N (0.1 ml) at 0 C. After stirring for 15 min, the mixture was warmed to r.t. for 30 min and then cooled to 0 C. The resulting solution was transferred dropwise via cannula to a solution of phthalimide (1.0 equiv; ca. 1 M in CH 2 Cl 2 ) and Et 3 N (1.3 equiv) at 0 C and the mixture was then warmed to r.t. over 1 h. The solution was diluted with H 2 O, extracted with CH 2 Cl 2 (3 ) before being dried over Na 2 SO 4, and then concentrated to give crude product that was purified using recrystallization. For samples with appreciable amounts of phthalimide present, the crude was dissolved with CH 2 Cl 2, diluted with 1 M NaOH, extracted with CH 2 Cl 2 (3 ) before being dried over Na 2 SO 4, then concentrated before being purified by recrystallization. 4) Synthesis of 1l, 1p S-43

45 Following a literature report 4, NaH (1.5 eq.) was added to a solution of 7-hydroxycoumarin (1.0 eq.) in anhydrous DMF (0.3 M). The mixture was allowed to stir at room temperature over 1h, followed by the addition of freshly prepared O-(mesitylsulfonyl)hydroxylamine(1.2 eq.). The reaction mixture was further stirred at room temperature for 12h. Upon completion, the mixture was cooled to 0, followed by quenching with water and extracted with ethyl acetate. The combined organic layer was dried over Na 2 SO 4, concentrated under reduced pressure to give the crude product N-aryloxyamine. In a 20 ml round-bottom flask, the crude product N-aryloxyamine (1.0 eq.) was dissolved in dichloromethane (0.2 M). The flask was cooled in an ice bath, to which acetic anhydride (2.0 eq.) was slowly added. The ice bath was allowed to warm to room temperature and the mixture was stirred for 3 h at room temperature. The reaction mixture was concentrated under reduced pressure and purified by flash silica gel column chromatography to give the corresponding N-acetyl aryloxyamine. 5) Synthesis of 1q 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (50mg), Succinic anhydride (20mg) and 4-(dimethylamino)pyridine (5mg) were dissolved in 2 ml methylene chloride. To this, 15μL Et 3 N was added. The solution was stirred overnight at rt, After the reaction was finished, removed the solvent by rotary evaporation. Then 7-(aminooxy)-2H-chromen-2-one (35mg), O-(7-Azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate (50mg), Et 3 N (15μL) and DMF (1mL) were added. The solution was stirred overnight at room temperature. After the reaction, 5 ml water was added and extracted with DCM. After drying with MgSO 4, the solvent was removed by rotary evaporation and the product isolated by column S-44

46 chromatography as a white solid. Yield of two steps: 45%. Characterization Data N-phenoxyacetamide, 1a, white solid, yield: 60% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.32 (t, J = 7.9 Hz, 2H), 7.01 (t, J = 7.6 Hz, 3H), 1.92 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ , , , , , N-phenoxypivalamide, 1b, white solid, yield: 48% 1 H NMR (300 MHz, DMSO-d 6 ): δ (s, 1H), 7.32 (t, J = 7.8 Hz, 2H), 7.00 (dd, J = 14.3, 7.6 Hz, 3H), 1.20 (s, 9H); 13 C NMR (75 MHz, DMSO-d 6 ): δ , , , , , 38.04, N-phenoxybenzamide, 1c, white solid, yield: 48% 1 H NMR (300 MHz, DMSO-d 6 ): (s, 1H), (m, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 7.3 Hz, 2H), (m, 2H), 7.06 (dd, J = 16.8, 7.9 Hz, 3H); 13 C NMR (75 MHz, DMSO-d 6 ): δ , , , , , , , N-(p-tolyloxy)acetamide, 1d, white solid, yield: 45% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.10 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 7.9 Hz, 2H), 2.24 (s, 3H), 1.90 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ , , , , , 20.52, N-(4-(tert-butyl)phenoxy)acetamide, 1e, white solid, yield: 45% 1 H NMR (400 MHz, Acetone-d 6 ): δ (s, 1H), 7.33 (d, J = 7.9 Hz, 2H), 6.97 (d, J S-45

47 = 7.7 Hz, 2H), 1.95 (s, 3H), 1.29 (s, 9H); 13 C NMR (101 MHz, Acetone-d 6 ): δ , , , , , 33.79, 30.95, N-(4-fluorophenoxy)acetamide, 1f, white solid, yield: 50% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.14 (t, J = 8.7 Hz, 2H), 7.03 (dd, J = 8.4, 4.2 Hz, 2H), 1.90 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ , (J = Hz), , (J = 24.2 Hz), (J=8.1 Hz), N-(4-chlorophenoxy)acetamide, 1g, white solid, yield: 45% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 1.91 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ , , , , , Methyl 4-(acetamidooxy)benzoate, 1h, white solid, yield: 47% 1 H NMR (400 MHz, DMSO) δ (s, 1H), 7.94 (d, J = 8.7 Hz, 1H), 7.13 (d, J = 8.5 Hz, 1H), 3.83 (s, 1H), 1.94 (s, 1H); 13 C NMR (101 MHz, DMSO) δ , , , , , , 52.37, N-(o-tolyloxy)acetamide, 1i, white solid, yield: 43% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.15 (t, J = 7.7 Hz, 2H), 6.99 (d, J = 8.0 Hz, 1H), 6.92 (t, J = 7.3 Hz, 1H), 2.21 (s, 3H), 1.92 (s, 3H) ; 13 C NMR (101 MHz, DMSO-d 6 ): δ , , , , , , , 19.44, N-(m-tolyloxy)acetamide, 1j, white solid, yield: 50% S-46

48 1 H NMR (400 MHz, Acetone-d 6 ): δ (s, 1H), 7.16 (t, J = 7.0 Hz, 1H), 6.85 (d, J = 14.0 Hz, 3H), 2.29 (s, 3H), 1.97 (s, 3H); 13 C NMR (101 MHz, Acetone-d 6 ): δ , , , , , , , 20.54, N-(3-fluorophenoxy)acetamide, 1k, white solid, yield: 35% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.34 (dd, J = 15.4, 8.0 Hz, 1H), (m, 3H), 1.92 (s, 3H); 13 C NMR (101MHz, DMSO-d 6 ): δ , (J = Hz), (J=10.6 Hz), (J = 10.2 Hz), , (J = 21.4 Hz), (J = 26.7 Hz), N-(4-methoxyphenoxy)acetamide, 1l, brown solid, yield: 45% 1 H NMR (400 MHz, DMSO-d 6 ) δ (s, 1H), 6.94 (d, J = 8.6 Hz, 1H), 6.87 (d, J = 8.7 Hz, 1H), 3.71 (s, 1H), 1.88 (s, 1H); 13 C NMR (101 MHz, DMSO-d 6 ) δ , , , , , 55.89, 19.89; HRMS (ESI) calculated for C 9 H 12 NO 3 [M+H] + : ; Found: N-(3-chlorophenoxy)acetamide, 1m, white solid, yield: 40% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.33 (t, J = 8.3 Hz, 1H), 7.08 (m, 2H), 6.99 (d, J = 8.1 Hz, 1H), 1.92 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ , , , , , , , N-(3-bromophenoxy)acetamide, 1n, white solid, yield: 30% 1 H NMR (400 MHz, DMSO-d 6 ): δ (s, 1H), 7.27 (t, J = 8.2 Hz, 1H), 7.21 (d, J = 5.4 Hz, 2H), 7.03 (d, J = 8.1 Hz, 1H), 1.92 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ , , , , , , , % N-(naphthalen-2-yloxy)acetamide, 1o, white solid, yield: S-47

49 1 H NMR (400 MHz, DMSO-d 6 ) : δ (s, 1H), 7.87 (dd, J = 17.2, 9.1 Hz, 3H), 7.48 (t, J = 7.4 Hz, 1H), 7.40 (dd, J = 13.9, 5.8 Hz, 2H), 7.27 (d, J = 8.9 Hz, 1H), 1.98 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) : δ , , , , , , , , , , , N-((2-oxo-2H-chromen-7-yl)oxy)acetamide, 1p, white solid, yield: 30% 1 H NMR (500 MHz, MeOD) : δ 7.90 (d, J = 9.5 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), (m, 2H), 6.31 (d, J = 9.5 Hz, 1H), 2.07 (s, 3H); 13 C NMR (126 MHz, MeOD) : δ , , , , , , , , , 19.30; HRMS (ESI) calculated for C 11 H 10 NO 4 [M+H] + : ; Found: q, white solid, yield: 45%. (S)-2-((4-oxo-4-(((2-oxo-2H-chromen-7-yl)oxy)amino)butanoyl)oxy)-3-(palmitoy loxy)propyl (2-(trimethylammonio)ethyl) phosphate 1 H NMR (400 MHz, MeOD): δ 7.92 (d, J = 9.5 Hz, 1H), 7.62 (d, J = 8.5 Hz, 1H), (m, 2H), 6.32 (d, J = 9.5 Hz, 1H), 5.32 (s, 1H), 4.62 (s, 2H), 4.41 (dd, J = 12.0, 3.6 Hz, 1H), (m, 3H), 4.07 (t, J = 5.1 Hz, 2H), (m, 2H), 3.23 (d, J = 8.9 Hz, 8H), 2.79 (d, J = 5.8 Hz, 2H), 2.62 (t, J = 6.2 Hz, 2H), (m, 2H), (m, 2H), 1.30 (dd, J = 18.5, 13.7 Hz, 23H), 0.91 (t, J = 6.8 S-48

50 Hz, 3H); 13 C NMR (101 MHz, MeOD): δ , , , , , , , , , , , 71.06, 70.98, 66.04, 63.65, 63.59, 62.05, 59.14, 59.09, 53.33, 53.29, 53.25, 33.35, 31.67, 29.38, 29.36, 29.33, 29.22, 29.07, 29.00, 28.77, 26.80, 24.49, 22.33, 13.04; 31 P NMR (162 MHz, MeOD): δ -0.55; HRMS (ESI) calculated for C 37 H 60 N 2 O 12 P [M+H] + : ; Found: (ethylthio)isoindoline-1,3-dione, 2a, white solid, yield: 80% 1 H NMR (500 MHz, CDCl 3 ): δ 7.94 (dd, J = 5.5, 3.0 Hz, 2H), 7.79 (dd, J = 5.5, 3 Hz, 2H), 2.92 (q, J = 7 Hz, 2H), 1.29 (t, J = 7 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ): δ 168.8, 134.8, 132.3, 124.1, 32.9, 13.4; HRMS (ESI) calculated for C 10 H 10 NO 2 S [M+H] + : ; Found: ((trifluoromethyl)thio)isoindoline-1,3-dione, 2b, white solid, yield: 70% 1 H NMR (400 MHz, CDCl 3 ): δ 8.03 (dd, J = 5.5, 3.1 Hz, 2H), 7.88 (dd, J = 5.6, 3.1 Hz, 2H); 13 C NMR (101 MHz, CDCl 3 ) δ , , , (q, J =314.8 Hz), ; 19 F NMR (376 MHz, CDCl 3 ): δ (s, 3F); HRMS (ESI) calculated for C 9 H 5 F 3 NO 2 S [M+H] + : ; Found: (decylthio)isoindoline-1,3-dione, 2c, white solid, yield: 76% 1 H NMR (500 MHz, CDCl 3 ): δ 7.92 (dd, J = 5.5, 3.0 Hz, 2H), 7.79 (dd, J = 5.5, 3 Hz, 2H), 2.89 (t, J = 7.5 Hz, 2H), (m, 2H), (m, 2H), (m, 12H), 0.87 (t, J = 7 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ): δ 168.6, 134.7, 132.3, 124.0, 38.8, 32.0, 29.63, 29.57, 29.4, 9.2, 28.6, 28.3, 22.8, 14.2; HRMS (ESI) calculated for C 18 H 26 NO 2 S [M+H] + : ; Found: S-49

51 2-(cyclohexylthio)isoindoline-1,3-dione, 2d, white solid, yield: 75% 1 H NMR (500 MHz, CDCl 3 ): δ 7.93 (dd, J = 5.5, 3.1 Hz, 2H), 7.78 (dd, J = 5.5, 3.0 Hz, 2H), 3.14 (tt, J = 10.9, 3.6 Hz, 1H), (m, 2H), (m, 2H), (m, 1H), (m, 2H), (m, 3H); 13 C NMR (126 MHz, CDCl 3 ): δ 168.8, 134.5, 132.0, 123.8, 49.4, 31.1, 25.5, 25.4; HRMS (ESI) calculated for C 14 H 16 NO 2 S [M+H] + : ; Found: (phenylthio)isoindoline-1,3-dione, 2e, yellow solid, yield: 82% 1 H NMR (500 MHz, CDCl 3 ): δ 7.93 (dd, J = 5.5, 3.1 Hz, 1H), 7.78 (dd, J = 5.5, 3.0 Hz, 1H), (m, 2H), (m, 3H); 13 C NMR (126 MHz, CDCl 3 ): δ 167.7, 135.1, 134.7, 132.1, 130.9, 124.0; HRMS (ESI) calculated for C 14 H 10 NO 2 S [M+H] + : ; Found: (phenylthio)isoindoline-1,3-dione, 2f, yellow solid, yield: 84% 1 H NMR (400 MHz, CDCl 3 ):δ 7.91 (dd, J = 5.5, 3.1 Hz, 1H), 7.76 (dd, J = 5.5, 3.1 Hz, 1H), (d, J = 7.9 Hz, 2H), 7.14 (d, J = 7.9 Hz, 2H), 2.32 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 168.0, 140.5, 134.7, 132.8, 132.2, 131.6, 130.2, 124.1, 21.4; HRMS (ESI) calculated for C 15 H 12 NO 2 S [M+H] + : ; Found: ((4-methoxyphenyl)thio)isoindoline-1,3-dione, 2g, white solid, yield: 71% 1 H NMR (500 MHz, CDCl 3 ): δ = 7.87 (dd, J=5.5, 3.0 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H), 7.73 (dd, J = 5.5, 3 Hz, 2H), 6.84 (d, J = 9.0 Hz, 2H), 3.78 (s, 3H); 13 C NMR S-50

52 (126 MHz, CDCl 3 ): δ 168.0, 161.6, 136.8, 134.7, 132.2, 125.7, 124.0, 114.9, 55.6; HRMS (ESI) calculated for C 15 H 12 NO 3 S [M+H] + : ; Found: ((4-fluorophenyl)thio)isoindoline-1,3-dione, 2h, yellow solid, yield: 80% 1 H NMR (400 MHz, CDCl 3 ):δ 7.91 (dd, J = 5.5, 3.1 Hz, 2H), 7.77 (dd, J = 5.5, 3.0 Hz, 2H), (m, 2H), (m, 2H); 13 C NMR (101 MHz, CDCl 3 ):δ 167.6, 165.0, 162.5, 135.6(J = 20 Hz), 134.7, 131.9, 124.0, 116.5(J =44 Hz); HRMS (ESI) calculated for C 14 H 9 FNO 2 S [M+H] + : ; Found: ((4-chlorophenyl)thio)isoindoline-1,3-dione, 2i, yellow solid, yield: 82% 1 H NMR (300 MHz, CDCl 3 ):δ 7.93 (dd, J = 5.5, 3.1 Hz, 2H), 7.79 (dd, J = 5.5, 3.1 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H); 13 C NMR (75 MHz, CDCl 3 ):δ 167.5, 135.8, 134.8, 133.3, 132.8, 131.8, 129.5, 124.1; HRMS (ESI) calculated for C 14 H 9 ClNO 2 S [M+H] + : ; Found: ((4-bromophenyl)thio)isoindoline-1,3-dione, 2j, yellow solid, yield: 81% 1 H NMR (400 MHz, CDCl 3 ): δ 7.93 (dd, J = 5.5, 3.1 Hz, 2H), 7.79 (dd, J = 5.5, 3.1 Hz, 2H), (m, 4H); 13 C NMR (101 MHz, CDCl 3 ): δ 167.5, 134.8, 134.0, 132.7, 132.5, 131.9, 124.1, 123.9; HRMS (ESI) calculated for C 14 H 9 BrNO 2 S [M+H] + : ; Found: S-51

53 2-(hexadecylthio)isoindoline-1,3-dione, 2k, white solid, yield: 76% 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 2H), (m, 2H), (m, 3H), 1.41 (dd, J = 14.0, 7.2 Hz, 2H), (m, 27H), 0.89 (t, J = 6.8 Hz, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ , , , , 38.66, 31.93, 29.68, 29.66, 29.62, 29.55, 29.44, 29.36, 29.12, 28.46, 28.14, 22.70, 14.13; HRMS (ESI) calculated for C 24 H 38 NO 2 S [M+H] + : ; Found: (tert-butylthio)isoindoline-1,3-dione, 2l, white solid, yield:30% 1 H NMR (500 MHz, CDCl 3 ) δ 7.93 (dd, J = 5.5, 3.1 Hz, 2H), 7.78 (dd, J = 5.5, 3.1 Hz, 2H), 1.35 (s, 9H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , 51.03, 29.36; HRMS (ESI) calculated for C 12 H 13 NNaO 2 S [M+Na] + : ; Found: (E)-N-(ethyl(2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3aa, white solid, yield: 92% 1 H NMR (500 MHz, CDCl 3 ): δ (m, 1H), 7.24 (dd, J = 7.9, 1.6 Hz, 1H), 6.99 (dd, J = 8.4, 0.9 Hz, 1H), (m, 1H), (m, 2H), 2.14 (s, 3H), 1.25 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ): δ , , , , , , , 42.79, 24.39, 7.78; HRMS (ESI) calculated for C 10 H 12 NO 2 S [M H] : ; Found: (E)-N-(ethyl(2-hydroxyphenyl)- 4 -sulfanylidene)pivalamide, 3ba, white solid, yield: 80% 1 H NMR (500 MHz, CD 2 Cl 2 ) δ 7.45 (t, J = 7.8 Hz, 1H), 7.29 (dd, J = 7.8, 1.3 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.95 (t, J = 7.8 Hz, 1H), 3.33 (tt, J = 14.7, 7.4 Hz, 1H), S-52

54 3.15 (dq, J = 14.8, 7.4 Hz, 1H), (m, 12H); 13 C NMR (126 MHz, CD 2 Cl 2 ) δ , , , , , , , 43.76, 39.93, 28.02, 6.93; HRMS (ESI) calculated for C 13 H 20 NO 2 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxyphenyl)- 4 -sulfanylidene)benzamide, 3ca, white solid, yield: 83% 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 1H), 7.46 (t, J = 7.4 Hz, 2H), (m, 2H), (m, 2H), 3.33 (tdd, J = 12.9, 7.4, 5.6 Hz, 2H), 1.30 (t, J = 7.4 Hz, 3H); 13 C NMR (101 MHz, CDCl 3 ) δ175.74, , , , , , , , , , , , 43.38, 7.75; HRMS (ESI) calculated for C 15 H 16 NO 2 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxy-5-methylphenyl)- 4 -sulfanylidene)acetamide, 3da, white solid, yield: 90% 1 H NMR (500 MHz, CD 2 Cl 2 ) δ 7.26 (dd, J = 8.3, 1.8 Hz, 1H), 7.09 (d, J = 1.4 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), (m, 2H), 2.30 (s, 3H), 2.09 (s, 3H), 1.25 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CD 2 Cl 2 ) δ , , , , , , , 43.21, 23.79, 19.86, 7.40; HRMS (ESI) calculated for C 11 H 16 NO 2 S [M+H] + : ; Found: (E)-N-((5-(tert-butyl)-2-hydroxyphenyl)(ethyl)- 4 -sulfanylidene)acetamide, 3ea, white solid, yield: 90% 1 H NMR (500 MHz, CDCl 3 ) δ 7.35 (dd, J = 8.7, 2.4 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 6.80 (d, J = 8.7 Hz, 1H), (m, 2H), 2.12 (s, 3H), (m, 12H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , , , , 43.13, 34.15, 31.21, 24.24, 14.10, 7.87; HRMS (ESI) calculated for C 14 H 22 NO 2 S [M+H] + : ; Found: S-53

55 (E)-N-(ethyl(5-fluoro-2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3fa, white solid, yield: 85% 1 H NMR (400 MHz, CD 2 Cl 2 ) δ (m, 2H), 6.82 (dd, J = 8.6, 4.4 Hz, 1H), (m, 2H), 2.10 (s, 3H), 1.25 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CD 2 Cl 2 ) δ , (J = Hz), ( J = Hz), ( J = Hz), ( J = 22.7 Hz), ( J = 7.6 Hz) (J = 23.9 Hz), 42.82, 23.88, 7.41; HRMS (ESI) calculated for C 10 H 13 FNO 2 S [M+H] + : ; Found: (E)-N-((5-chloro-2-hydroxyphenyl)(ethyl)- 4 -sulfanylidene)acetamide, 3ga, white solid, yield: 86% 1 H NMR (500 MHz, MeOD) δ 7.47 (d, J = 2.5 Hz, 1H), 7.42 (dd, J = 8.7, 2.5 Hz, 1H), 6.96 (d, J = 8.7 Hz, 1H), (m, 1H), (m, 1H), 2.14 (s, 3H), 1.25 (t, J = 7.3 Hz, 3H); 13 C NMR (126 MHz, MeOD) δ , , , , , , , 40.34, 22.84, 6.44; HRMS (ESI) calculated for C 10 H 13 ClNO 2 S [M+H] + : ; Found: Methyl (E)-3-(N-acetyl-S-ethylsulfinimidoyl)- 4 -hydroxybenzoate, 3ha, white solid, yield: 89% 1 H NMR (500 MHz, CDCl 3 ) δ 8.83 (s, 1H), 7.98 (dd, J = 7.1, 2.0 Hz, 1H), (m, 1H), 6.82 (d, J = 8.7 Hz, 1H), 3.86 (s, 3H), (m, 2H), 2.16 (s, 3H), 1.23 (t, J = 7.4, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , , , , , 52.09, 43.01, 24.20, 7.53; HRMS (ESI) calculated for C 12 H 16 NO 4 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxy-3-methylphenyl)- 4 -sulfanylidene)acetamide, 3ia, white solid, yield: 89% S-54

56 1 H NMR (500 MHz, MeOD) δ 7.35 (dd, J = 13.7, 7.7 Hz, 2H), 6.97 (t, J = 7.7 Hz, 1H), (m, 1H), (m, 1H), 2.27 (s, 3H), 2.11 (s, 3H), 1.24 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, MeOD) δ , , , , , , , 41.63, 22.76, 14.59, 6.66; HRMS (ESI) calculated for C 11 H 16 NO 2 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxy-4-methylphenyl)- 4 -sulfanylidene)acetamide, 3ja, white solid, 3ja:3ja =1.1:1, yield: 89% 1 H NMR (500 MHz, CDCl 3 ) δ 7.12 (d, J = 8.2 Hz, 1H), 6.72 (s, 1H), 6.71 (d, J = 7.6 Hz, 1H), (m, J = 12.8, 7.4, 5.5 Hz, 2H), 2.29 (s, 3H), 2.13 (s, 3H), 1.22 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , , , , 43.27, 24.18, 21.44, 7.69; HRMS (ESI) calculated for C 11 H 16 NO 2 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxy-6-methylphenyl)- 4 -sulfanylidene)acetamide, 3ja, white solid, 3ja:3ja =1.1:1, yield: 89% 1 H NMR (500 MHz, CDCl 3 ) δ 7.29 (dd, J = 15.0, 7.1 Hz, 1H), 6.83 (d, J = 8.3 Hz, 1H), 6.74 (d, J = 7.5 Hz, 1H), (m, 2H), 2.46 (s, 3H), 2.13 (s, 3H), 1.26 (d, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , , , 42.57, 24.26, 20.03, 7.90; HRMS (ESI) calculated for C 11 H 16 NO 2 S [M+H] + : ; Found: (E)-N-(ethyl(4-fluoro-2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3ka, white solid, 3ka:3ka =1.05:1, yield: 84% 1 H NMR (400 MHz, CD 2 Cl 2 ) δ 8.99 (s, 1H), 7.27 (dd, J = 8.8, 6.1 Hz, 1H), 6.61 (td, J = 8.6, 2.5 Hz, 1H), 6.48 (dd, J = 10.3, 2.5 Hz, 1H), (m, 2H), 2.14 (s, 3H), 1.23 (t, J = 7.4 Hz, 3H); 13 C NMR (101 MHz, CD 2 Cl 2 ) δ , (J=353.5 Hz), (J = 13.1 Hz), (J = 12.1 Hz), (J = Hz), (J = 23.2 Hz), (J = 25.2 Hz), 42.95, 24.01, 7.43; HRMS (ESI) calculated for C 10 H 13 FNO 2 S [M+H] + : ; Found: S-55

57 (E)-N-(ethyl(2-fluoro-6-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3ka, white solid, 3ka:3ka =1.05:1, yield: 84% 1 H NMR (400 MHz, CD 2 Cl 2 ) δ 7.43 (dd, J = 15.2, 8.3 Hz, 1H), 6.79 (d, J = 8.5 Hz, 1H), 6.70 (t, J = 9.0 Hz, 1H), 3.41 (dq, J = 14.7, 7.4 Hz, 1H), 3.19 (dq, J = 14.5, 7.3 Hz, 1H), 2.13 (s, 3H), 1.29 (t, J = 7.3 Hz, 3H); 13 C NMR (101 MHz, CD 2 Cl 2 ) δ , , , , (J = 11.1 Hz), , (J = 21.2 Hz), 43.61, 23.81, 6.63; HRMS (ESI) calculated for C 10 H 13 FNO 2 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxy-5-methoxyphenyl)- 4-sulfanylidene)acetamide, colorless oil, 3la, yield: 88% 1 H NMR (500 MHz, CDCl 3 ) δ 6.90 (dd, J = 9.0, 3.0 Hz, 1H), 6.81 (d, J = 9.0 Hz, 1H), 6.78 (d, J = 3.0 Hz, 1H), 3.73 (s, 3H), (m, 2H), 2.13 (s, 3H), 1.24 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , , , , 55.97, 42.81, 24.26, 7.85; HRMS (ESI) calculated for C 11 H 16 NO 3 S [M+H] + : ; Found: (E)-N-((4-chloro-2-hydroxyphenyl)(ethyl)- 4 -sulfanylidene)acetamide, 3ma, white solid, 3ma:3ma =1:1, yield: 85% 1 H NMR (500 MHz, MeOD) δ 7.50 (d, J = 8.5 Hz, 1H), 7.07 (dd, J = 8.5, 2.0 Hz, 1H), 7.00 (d, J = 2.0 Hz, 1H), (m, 1H), (m, 1H), 2.12 (s, 3H), 1.25 (t, J = 7.3 Hz, 3H); 13 C NMR (126 MHz, MeOD) δ , , , , , , , 40.41, 22.79, 6.48; HRMS (ESI) calculated for C 10 H 13 ClNO 2 S [M+H] + : ; Found: (E)-N-((2-chloro-6-hydroxyphenyl)(ethyl)- 4 -sulfanylidene)acetamide, white solid, 3ma:3ma =1:1, yield: 85% 3ma, S-56

58 1 H NMR (400 MHz, CD 2 Cl 2 ) δ 7.39 (t, J = 8.2 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.5 Hz, 1H), 3.44 (dt, J = 14.7, 7.3 Hz, 1H), (m, 1H), 2.13 (s, 3H), 1.32 (t, J = 7.4 Hz, 3H); 13 C NMR (101 MHz, CD 2 Cl 2 ) δ , , , , , 43.02, 23.94, 6.89; HRMS (ESI) calculated for C 10 H 13 ClNO 2 S [M+H] + : ; Found: (E)-N-((4-bromo-2-hydroxyphenyl)(ethyl)- 4 -sulfanylidene)acetamide, 3na, white solid, 3na:3na =1:1, yield: 86% 1 H NMR (500 MHz, MeOD) δ 7.43 (d, J = 8.5 Hz, 1H), 7.22 (dd, J = 8.5, 1.8 Hz, 1H), (m, 1H), (m, 1H), 3.18 (dd, J = 13.1, 7.3 Hz, 1H), 2.12 (s, 3H), 1.25 (t, J = 7.3 Hz, 3H); 13 C NMR (126 MHz, MeOD) δ , , , , , , , 40.32, 22.79, 6.48; HRMS (ESI) calculated for C 10 H 13 BrNO 2 S [M+H] + : ; Found: (E)-N-((2-bromo-6-hydroxyphenyl)(ethyl)- 4 -sulfanylidene)acetamide, 3na, white solid, 3na:3na =1:1, yield: 86% 1 H NMR (400 MHz, CD 2 Cl 2 ) δ 7.31 (t, J = 8.1 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 3.44 (dq, J = 14.7, 7.4 Hz, 1H), 3.27 (dq, J = 14.6, 7.4 Hz, 1H), 2.13 (s, 3H), 1.33 (t, J = 7.3 Hz, 3H); 13 C NMR (101 MHz, CD 2 Cl 2 ) δ , , , , , , 43.09, 23.96, 7.04; HRMS (ESI) calculated for C 10 H 13 BrNO 2 S [M+H] + : ; Found: (E)-N-(ethyl(2-hydroxynaphthalen-1-yl)- 4 -sulfanylidene)acetamide, 3oa, white solid, yield: 89% 1 H NMR (500 MHz, CDCl 3 ) δ 7.97 (d, J = 8.5 Hz, 1H), 7.88 (d, J = 9.0 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), (m, 1H), 7.38 (dd, J = 11.1, 4.0 Hz, 1H), 7.13 (d, J = 9.0 Hz, 1H), (m, 1H), 3.21 (dd, J = 13.0, 7.4 Hz, 1H), 2.17 (s, 3H), 1.22 (t, J = 7.4 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ , , , , , , , , , , , 42.90, 24.34, 7.51; HRMS (ESI) calculated for C 14 H 16 NO 2 S [M+H] + : ; Found: S-57

59 (Z)-N-((2-hydroxyphenyl)(trifluoromethyl)- 4 -sulfanylidene)acetamide, 3ab, white solid, yield: 85% 1 H NMR (400 MHz, CDCl 3 ):δ (s, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.01 (dd, J = 7.8, 3.8 Hz, 2H), 2.25 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ , , , , ( J = Hz), , , , 24.41; 19 F NMR (376 MHz, CDCl 3 ):δ (s, 3F); HRMS (ESI) calculated for C 9 H 7 F 3 NO 2 S [M H] : ; Found: ; IR (cm -1 ): 1541, 1452, 1363, 1315, 1296, 1190, 1097, 1003, 954, 800, 767, 754. (E)-N-(decyl(2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3ac, white solid, yield: 85% 1 H NMR (500 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 3.11 (dd, J = 13.5, 7.3 Hz, 2H), 2.13 (s, 3H), (m, 2H), (m, 2H), (m, 12H), 0.83 (t, J = 7.0 Hz, 3H); 13 C NMR (126 MHz, CDCl 3 ): δ , , , , , , , 48.63, 31.83, 29.39, 29.25, 29.20, 28.96, 28.29, 24.40, 23.33, 22.63, 14.08; HRMS (ESI) calculated for C 18 H 28 NO 2 S [M H] : ; Found: (E)-N-(cyclohexyl(2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3ad, white solid, yield: 76% 1 H NMR (500 MHz, CDCl 3 ): δ (m, 1H), 7.18 (dd, J = 7.8, 1.5 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), (m, 1H), 3.32 (tt, J = 11.4, 3.5 Hz, 1H), 2.12 (s, 3H), (m, 1H), (m, 2H), 1.79 (dd, J = 7.9, 3.8 Hz, 1H), (m, 1H), 1.39 (ddd, J = 23.9, 12.1, 3.5 Hz, 1H), (m, 2H), 1.17 (ddd, J = 15.1, 8.8, 2.9 Hz, 2H). 13 C NMR (126 MHz, CDCl 3 ): δ , , , , , , , 60.05, 27.11, 26.53, 25.44, 25.33, 25.20, 24.63; HRMS (ESI) calculated for C 14 H 18 NO 2 S [M H] : ; Found: S-58

60 (E)-N-((2-hydroxyphenyl)(phenyl)- 4 -sulfanylidene)acetamide, 3ae, white solid, yield: 67% 1 H NMR (500 MHz, CDCl 3 ): δ (m, 2H), (m, 3H), 7.33 (t, J = 7.7 Hz, 2H), 6.92 (d, J = 8.1 Hz, 1H), 6.88 (t, J = 7.6 Hz, 1H), 2.18 (s, 3H). 13 C NMR (126 MHz, CDCl 3 ): δ , , , , , , , , , , , 24.34; HRMS (ESI) calculated for C 14 H 12 NO 2 S [M H] : ; Found: (E)-N-((2-hydroxyphenyl)(p-tolyl)- 4 -sulfanylidene)acetamide, 3af, white solid, yield: 85% 1 H NMR (400 MHz, CDCl 3 ) : δ 7.62 (d, J = 8.3Hz, 2H), (m, 1H), (m, 3H), 6.97 (dd, J = 8.4, 1.1 Hz, 1H), 6.87 (td, J = 8.0, 1.2 Hz, 1H), 2.35 (s, 3H), 2.17 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ , , , , , , , , , , , 24.27, 21.41; HRMS (ESI) calculated for C 15 H 14 NO 2 S [M H] : ; Found: ; IR (cm -1 ): 2916, 2846, 1585, 1541, 1521, 1508, 1490, 1448, 1363, 1298, 1280, 1219, 1178, 1157, 1116, 1006, 970, 848, 833. (E)-N-((2-hydroxyphenyl)(4-methoxyphenyl)- 4 -sulfanylidene)acetamide, 3ag, white solid, yield: 80% 1 H NMR (500 MHz, CDCl 3 ): δ 7.68 (d, J = 8.9 Hz, 1H), (m, 1H), (m, 1H), 6.93 (m, 3H), 6.86 (t, J = 7.5 Hz, 1H), 3.77 (s, 3H), 2.14 (s, 3H). 13 C NMR (126 MHz, CDCl 3 ): δ , , , , , , , , , , 55.61, 24.30; HRMS (ESI) calculated for C 15 H 14 NO 3 S [M S-59

61 H] : ; Found: (E)-N-((4-fluorophenyl)(2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3ah, white solid, yield: 75% 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), 7.39 (ddd, J = 8.6, 7.3, 1.6 Hz, 1H), (m, 1H), (m, 2H), 6.99 (dd, J = 8.4, 1.0 Hz, 1H), (m, 1H), 2.18 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ): δ , , , , , (J=4.5 Hz), , (J=7.1 Hz), , , , 24.22; HRMS (ESI) calculated for C 14 H 11 FNO 2 S [M H] : ; Found: ; IR (cm -1 ): 2922, 2850, 1654, 1587, 1558, 1541, 1521, 1490, 1448, 1365, 1321, 1300, 1230, 1155, 1010, 831, 754. (E)-N-((4-chlorophenyl)(2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, 3ai, white solid, yield: 70% 1 H NMR (400 MHz, CDCl 3 ): δ 7.68 (d, J = 8.7 Hz, 2H), (m, 3H), 7.28 (dd, J = 8.5, 2.0 Hz, 1H), 7.00 (d, J = 8.3 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 2.19 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ , , , , , , , , , , , 24.19; HRMS (ESI) calculated for C 14 H 11 ClNO 2 S [M H] : ; Found: ; IR (cm -1 ): 2920, 2850, 1734, 1653, 1635, 1577, 1558, 1471, 1450, 1363, 1298, 1273, 1155, 1089, 1008, 833,812, 792, 752. (E)-N-((4-bromophenyl)(2-hydroxyphenyl)- 4 -sulfanylidene)acetamide, S-60 3aj,

62 white solid, yield: 68% 1 H NMR (500 MHz, DMSO): δ 7.72 (m, 3H), (m, 2H), (m, 1H), (m, 1H), 6.93 (d, J = 7.6 Hz, 1H), 1.98 (s, 3H); 13 C NMR (126 MHz, DMSO): δ , , , , , , , , , , , 25.23; HRMS (ESI) calculated for C 14 H 11 BrNO 2 S [M H] : ; Found: (E)-N-(ethyl(7-hydroxy-2-oxo-2H-chromen-8-yl)- 4 -sulfanylidene)acetamide, 3pa, white solid, yield: 80% 1 H NMR (300 MHz, CD 2 Cl 2 ):δ (m, 1H), 7.58 (d, J = 19.0 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 6.23 (d, J = 9.2 Hz, 1H), 3.53 (dd, J = 12.7, 6.5 Hz, 1H), 3.27 (dd, J = 12.7, 6.5 Hz, 1H), 2.16 (s, 3H), (m, 3H); 13 C NMR (126 MHz, CD 2 Cl 2 ): δ , , , , , , , , , 43.59, 24.23, 7.00; HRMS (ESI) calculated for C 13 H 14 NO 4 S [M+H] + : ; Found: S-61

63 Supplementary discussion Synthesis of deuterated substrate 1a-d 8 Following a literature report 1, in a 50mL round-bottom flask, N-hydroxyphthalimide (1.0 eq.), cooper (I) chloride (1.0 eq.), freshly activated 4 Å molecular sieves (250mg/mmol), and D5-phenylboronic acid (2.0 eq.) were combined in 1,2-dichloroethane(0.2 M). The pyridine (1.1 eq.) was then added to the suspension. The reaction mixture was open to the atmosphere and stirred at room temperature over 24 h. Upon completion, filtered through a celite pad, the filtrate was concentrated to give the crude deuterated N-aryloxyphthalimides. Hydrazine monohydrate (3.0 eq.) was added to the solution of the crude deuterated N-aryloxyphthalimide (1.0eq.) in 10% MeOH in CHCl 3 (0.1 M). The reaction was allowed to stir at room temperature over 12 h. Upon completion, the reaction mixture was filtered off and washed with CH 2 Cl 2. The filtrate was concentrated under reduced pressure, and purified by flash silica gel column chromatography to give the corresponding deuterated N-aryloxyamine. To a solution of deuterated N-aryloxyamine and D4-acetic acid (1 eq.) in CH 2 Cl 2 (0.4 M) at 0 were added HOBt (1.1 eq.) and EDCI (1.1 eq.). The reaction mixture was stirred at room temperature for 10 h, then washed with 5% aqueous HCl ( ml), 5% aqueous NaHCO 3 (20.0 ml), H 2 O (20.0 ml), and brine (20.0 ml), and dried (Na 2 SO 4 ). Purification by flash chromatography afforded the corresponding deuterated N-phenoxyamide (1a-d 8 ) as a white solid. 1 H NMR (400 MHz, DMSO) δ (s, 1H); 13 C NMR (101 MHz, DMSO) δ , , (t, J = 24.3 Hz), (t, J = 24.2 Hz), (t, J = 24.1 Hz), (t, J = 19.4 Hz); HRMS (ESI) calculated for C 8 H 2 D 8 NO 2 [M+H] + : ; Found: Cross-over Experiment S-62

64 Supplementary Figure 36. Cross-over experiments. (a) Reaction conditions: 1a (0.02 mmol), 1a-d 8 (1 eq.), 2a (2.4 eq.) and CsOAc (1 eq.) in MeOH at room temperature for 3 h. (b) Reaction conditions: 1c (0.1 mmol), 1d (1 eq.), 2a (2.4 eq.) and CsOAc (1 eq.) in MeOH at room temperature for 3 h. (c) HR-MS spectrum of (a). (d) HR-MS spectrum of (b). we carried out the cross-over experiments using a 1:1 mixture of N-phenoxyacetamide 1a and its analogue 1a-d 8 under the standard condition, only the intramolecular rearrangement products 3aa and 3aa-d 7 were obtained (Supplementary Fig. 36a), suggesting an intramolecular process. The cross-over experiment between 1c, 1d and 2a confirmed this conclusion (Supplementary Fig. 36b). DFT Calculations COMPUTATIONAL DETAILS S-63

65 All the calculations were performed with the Gaussian09 suite of programs. 5 Geometry optimization and energy calculations were conducted with B3LYP. 6 LANL2DZ + d (0.289) basis set with ECP was used for I and 6-31G (d) basis set was used for atoms. 7-9 To verify the stationary points as minima or transition states, vibration frequency calculation at the same level of theory was performed for each structure. The zero-point energy, thermal energy, entropy, and free energy were also derived from vibration frequency. Single point energies were calculated at the B3LYP-D 10 /SDD G (d, p) level. A solvent correction for methanol at 298 K was calculated by using SMD solvation model. 12 As shown in Fig. 2a, for the internal oxidants containing the X N bond (X=N, S, O), only when X is O, the desired phenol product can be obtained. When N H was replaced by N Me, no reaction occurred. Furthermore, base (such as CsOAc) was an indispensable component for this reaction (Supplementary Table 6). These results indicated that the acidity of the N H is important for this reaction and the N H bond might be deprotoned by the base to initiate the following reaction. 13 The N-sulfenylation step (TS1) was found to be the rate-determining step (RDS). By examining the structure of TS1, we envisioned that the energy barrier of nucleophilic substitution process could be influenced by the steric hindrance of the N-substituted thiophthalimides. DFT calculation revealed the activation free energy of the reaction between INT1 and N-t-butylthiophthalimide was indeed 8 kcal/mol higher (TS1 ) than that of N-ethylthiophthalimide, which implied that N-sulfenylation was unlikely to occur for the bulky N-t-butylthiophthalimide. The experiment was then conducted and confirmed the computational results (supplementary Fig. 37b). The calculation results speculated that the reaction process containing two main stages: (1) N-sulfenylation. (2) [2, 3] sigmatropic rearrangement and aromatization. First, the amide (NH) of the substrate could be deprotonated under weak basic conditions such as OAc 13 to form the intermediate INT1. Next, nucleophilic substitution by the intermediate INT1 to N-ethylthiophthalimide led to the formation of the N S bond (intermediate INT2) via TS1, and the computational results indicated that the barrier (25.7 kcal/mol) was accessible under reaction condition. Subsequently, [2,3]-sigmatropic rearrangement occurred through TS2 to form the intermediate INT3. Finally, the intermediate INT3 would easily tautomerize to the product. (supplementary Fig. 37a) S-64

66 Supplementary Figure 37. Mechanistic studies. (a) Free energy (enthalpy) profile of the cascade reaction (in kcal/mol). (b) The reaction of N-phenoxyacetamide 1a and N-tert-butylthiophthalimide 2l under the standard conditions. Cartesian coordinates (in Å) of related structures which calculated at the B3LYP/ Lanl2dz G(d) level of theory. substrate H C C C C C C H H H H H O N S-65

67 C C H H H O AcO- C C H H H O O AcOH C H H H C O H O C C C C C C H H H H H O N C C H H S-66

68 H O N-ethylthiophthalimide C C N O O C C C C H C H C H H S C H H C H H H N-t-butylthiophthalimide C C N O O C C C C H C H C H H S-67

69 S C C H H H C H H H C H H H TS1 C C C C C C H H H H H O N C C H H H O S C C H H H C C N S-68