Micelles-Enabled Photo-Assisted Selective Oxyhalogenation of Alkynes in Water Under Mild Conditions. Supporting Information

Size: px

Start display at page:

Download "Micelles-Enabled Photo-Assisted Selective Oxyhalogenation of Alkynes in Water Under Mild Conditions. Supporting Information"

Morris Baldwin
5 years ago
Views:

1 Micelles-Enabled Photo-Assisted Selective Oxyhalogenation of Alkynes in Water Under Mild Conditions Lucie Finck, Jeremy Brals, Bhavana Pavuluri, Fabrice Gallou, and Sachin Handa* Department of Chemistry, University of Louisville Louisville, KY 40292, USA Novartis Pharma AG Basel, Switzerland Supporting Information Content Page 1. Reaction Optimization S2-S4 2. Optimal General Procedure with Picture of Reaction Setup S4 3. Calculations and Procedure of E Factor and Recycle Studies S5-S6 4. NMR spectra S7-S25 S1

2 1. Reaction Optimization 1a. Surfactant Screening Entry 3 wt% aqueous surfactant % yield 3* 1 TPGS-750-M 69 2 FI-750-M 80 3 SDS 42 4 neat water 35 Conditions: 1 (0.5 mmol), 2 (1.0 mmol), eosin Y ( 5 mol%), 1.0 ml 3 wt% surfactant in H 2 O, Ar, 3h; *all yields are isolated. 1b. Catalyst Screening and Role of light Entry catalyst % yield 3* 1 eosin Y benzoyl peroxide 58 4 no catalyst, dark 9 Conditions: 1 (0.5 mmol), 2 (1.0 mmol), catalys (5 mol%), 1.0 ml 3 wt% FI-750-M in H 2 O, Ar, 3h; *all yields are isolated S2

3 1c. Role of Oxygen conditions: 1 (0.5 mmol), 2 (1.0 mmol), eosin Y (5.0 mol%), 1.0 ml 3 wt% FI-750-M in H 2 O, visible-light (9 W), rt, 3 h. Reaction under air: In a 4.0 ml reaction vial containing a PTFE-coated magnetic stir bar, NBS (2.0 equiv., 1.0 mmol, 178 mg), eosin YH + (5.0 mol%, mmol, 16.2 mg) and phenylacetylene (1.0 equiv., 0.5 mmol) were sequentially added. The reaction vial was closed with a rubber septum. 1.0 ml 3 wt% aqueous FI-750-M was added to the reaction mixture. Air balloon was introduced to the reaction to run a reaction under ambient air. The reaction mixture was placed in front of visible-light (9 W compact fluorescent bulb) and allowed to stir at room temperature for 3 h. After complete consumption of starting material, as monitored by TLC or GCMS, 1.0 ml ethyl acetate and 1.0 ml water was added to the reaction mixture, which was then gently stirred for 2 min. The organic layer was separated via centrifuge. This extraction was repeated using additional 1 ml EtOAc. The combined extracts were dried over anhydrous sodium sulfate and volatiles were evaporated under reduced pressure at room temperature to obtain crude product, which was further purified by flash chromatography (wet load in DCM) over silica gel using hexanes/ethyl acetate (9:1) as eluent. Pure product was obtained as oil, yield 25 mg (18%). Reaction in the presence of TEMPO: In a 4.0 ml reaction vial containing a PTFE-coated magnetic stir bar, NBS (2.0 equiv., 1.0 mmol, 178 mg), eosin YH + (5.0 mol%, mmol, 16.2 mg), TENPO (78 mg, 0.5 mmol), and phenylacetylene (1.0 equiv., 0.5 mmol) were sequentially added. The reaction vial was closed with a rubber septum. The reaction vial was closed with a rubber septum and subsequently evacuated and back-filled with argon. 1.0 ml volume of 3 wt% aqueous FI-750-M was added to the reaction mixture. The septum was wrapped with PTFE tape and black electrical tape. The reaction mixture was placed in front of visible-light (9 W compact fluorescent bulb) and allowed to stir at room temperature for 3 h. After complete consumption of starting material, as monitored by TLC or GCMS, 1.0 ml ethyl acetate and 1.0 ml water was added to the reaction mixture, which was then gently stirred for 2 min. The organic layer was separated via centrifuge. This extraction was repeated using additional 1 ml EtOAc. The combined extracts were dried over anhydrous sodium sulfate and volatiles were evaporated under reduced pressure at room temperature to obtain crude product, which was S3

further purified by flash chromatography (wet load in DCM) over silica gel using hexanes/ethyl acetate (9:1) as eluent. Pure product was obtained as oil, yield 48 mg (35%).

0 ml reaction vial containing a PTFE-coated magnetic stir bar, NBS (2.0 equiv., 1.0 mmol, 178 mg) or NCS (2.0 equiv., 1.0 mmol, 133.5 mg), eosin YH + (5.0 mol%, 0.025 mmol, 16.2 mg) and alkyne (1.

0 ml volume of 3 wt% aqueous FI- 750-M was added to the reaction mixture. The septum was wrapped with PTFE tape and black electrical tape.

4 further purified by flash chromatography (wet load in DCM) over silica gel using hexanes/ethyl acetate (9:1) as eluent. Pure product was obtained as oil, yield 48 mg (35%). Other numerous side unidentifiable side products were formed. 2. Optimal General Procedure of Catalytic Oxyhalogenation of Alkynes In a 4.0 ml reaction vial containing a PTFE-coated magnetic stir bar, NBS (2.0 equiv., 1.0 mmol, 178 mg) or NCS (2.0 equiv., 1.0 mmol, mg), eosin YH + (5.0 mol%, mmol, 16.2 mg) and alkyne (1.0 equiv., 0.5 mmol) were sequentially added. The reaction vial was closed with a rubber septum and subsequently evacuated and back-filled with argon. 1.0 ml volume of 3 wt% aqueous FI- 750-M was added to the reaction mixture. The septum was wrapped with PTFE tape and black electrical tape. The reaction mixture was irradiated under 9 W compact fluorescent bulb and allowed to stir at room temperature or 45 C. After complete consumption of starting material, as monitored by TLC or GCMS, 1.0 ml ethyl acetate and 1.0 ml water was added to the reaction mixture, which was then gently stirred for 2 min. The organic layer was separated via centrifuge. This extraction was repeated using additional 1.0 ml EtOAc. The combined extracts were dried over anhydrous sodium sulfate and volatiles were evaporated under reduced pressure at room temperature to obtain crude product, which was further purified by flash chromatography (wet load in DCM) over silica gel using hexanes/ethyl acetate as eluent. Note: For compound 14, the reaction was set up in a 1.8 ml vial. S4

5 3. E Factor and Recycle Studies i) Initial reaction: In a 4.0 ml reaction vial containing a PTFE-coated magnetic stir bar, NBS (2 equiv., 1 mmol, mg), eosin YH + (5 mol%, mmol, mg) and phenylacetylene (1 equiv., 0.5 mmol, 55 µl) were sequentially added. Reaction vial was closed with a rubber septum. Reaction vial was evacuated and back-filled with argon. A 1.0 ml volume of 3 wt% aqueous FI-750-M solution was added to the reaction mixture. Septum was sealed with Teflon tape and black electrical tape. The reaction mixture was irradiated with a 9 W compact fluorescent bulb and it was allowed to stir for 3 h at room temperature. After complete consumption of starting material as monitored by GCMS and TLC, 0.5 ml diethyl ether was added to the reaction mixture, which was then gently stirred for 2 min. Stirring was stopped and the organic layer was carefully taken out by Pasteur pipette. Another extraction was likewise performed using an additional 0.4 ml ether. The combined extracts were dried over anhydrous sodium sulfate and volatiles were removed under reduced pressure at room temperature to obtain crude product as an S5

6 orange oil. The crude product was purified by flash chromatography over silica gel using 1% ethyl acetate/hexanes as eluent. Pure product was obtained as a yellow oil, Rf = 0.42 (9:1, hexanes/ethyl acetate), yield 110 mg, 79%. ii) 1st recycle: To the well sparged (with argon) aqueous system (in a 4.0 ml reaction vial) obtained from above reaction, phenylacetylene (1.0 equiv., 0.5 mmol, 55 µl) and NBS (2.0 equiv., 1.0 mmol, 178 mg) were added under argon. Reaction vial was closed with a rubber septum. Reaction vial was evacuated and back-filled with argon. Septum was sealed with Teflon tape and black electrical tape. The reaction mixture was irradiated with a 9 W compact fluorescent bulb and it was allowed to stir for 3 h at room temperature. After complete consumption of starting material as monitored by GCMS and TLC, 0.5 ml ether was added to the reaction mixture, which was then gently stirred for 2 min. Stirring was stopped and the organic layer was carefully taken out by Pasteur pipette. Another extraction was likewise performed using an additional 0.4 ml ether. The combined extracts were dried over anhydrous sodium sulfate and volatiles were removed under reduced pressure at room temperature to obtain crude product as an orange oil. The crude product was purified by flash chromatography over silica gel using 1% ethyl acetate/hexanes as eluent. Pure product was obtained as a yellow oil, Rf = 0.42 (9:1, hexanes/ethyl acetate), yield 108 mg, 78%. iii) 2 nd, 3 rd, and 4 th recycle: For the 2 nd, 3 rd, and 4 th recycles, similar procedures were used as described above mg (70%), 108. mg (78%), and mg (77%) yields were respectively obtained. S6

7 4. NMR Spectra S7

8 1 H NMR (3) 3 1 H NMR (4) 4 S8

9 1 H NMR (5) 5 1 H NMR (6) 6 S9

10 1 H NMR (7) 7 S10

11 1 H NMR (8) 8 13 C NMR (8) 8 S11

12 1 H NMR (9) 9 S12

13 1 H NMR (10) C NMR (10) 10 S13

14 1 H NMR (11) 11 S14

15 1 H NMR (12) C NMR (12) 12 S15

16 1 H NMR (13) 13 1 H NMR (14) 14 S16

17 1 H NMR (15) 15 1 H NMR (16) 16 S17

18 1 H NMR (17) 17 S18

19 1 H NMR (18) C NMR (18) 18 S19

20 1 H NMR (19) C NMR (19) 19 S20

21 1 H NMR (20) 20 S21

22 1 H NMR (21) C NMR (21) S22 21

23 1 H NMR (22) 22 S23

24 1 H NMR (23) C NMR (23) 23 S24

25 1 H NMR (24) 24 S25

Micellar catalysis applied to sustainable ppm Au-catalyzed reactions in water at room temperature. Supporting information

Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 2017 Micellar catalysis applied to sustainable ppm Au-catalyzed reactions in water at room temperature