A Combination of Visible-light Photoredox and Metal Catalysis for the Mannich-type Reaction of N-Aryl Glycine Esters

Transcription

1 A Combination of Visible-light Photoredox and Metal Catalysis for the Mannich-type Reaction of -Aryl Glycine Esters Izumi kamura, 1 Soyoung Park,* 1 Ji Hoon Han, 1 Shunta otsu, 3 and Hiroshi Sugiyama* 1,2 1 Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-iwakecho, Sakyo-ku, Kyoto Institute for Integrated Cell-Material Sciences (icems), Kyoto University, Yoshida-Ushinomiyacho, Sakyo-ku, Kyoto Department of Industrial Chemistry, Faculty of Engineering, Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto (Received July 26, 2017; CL ; hs@kuchem.kyoto-u.ac.jp) Copyright The Chemical Society of Japan

2 Materials p-toluidine and ethyl bromoacetate were received from ACALAI TESQUE, IC. and used without further purification. 5-Aminofluorescein was purchased from Tokyo Chemical Industry Co., Ltd. (TCI) and used as received. InBr 3 was purchased from Sigma-Aldrich Co. LLC and used as received. Tetrahydrofuran, stabilizer free was received from Wako Pure Chemical Industries, Ltd. and used without further purification. All other chemicals and solvents were purchased from ACALAI TESQUE, IC., Sigma-Aldrich Co. LLC, Wako Pure Chemical Industries, Ltd., TCI or KAT CHEMICAL C. IC. and used without further purification. Methods MR spectra were obtained on a JEL JM ECA-600 spectrometer operating at 600 MHz for 1 H MR and 150 MHz for 13 C MR in CDCl 3 unless otherwise noted. Flash column chromatography was performed employing Wakogel 60 ( µm, Wako Pure Chemical Industries, Ltd.). Silica-gel preparative thin-layer chromatography (PTLC) was performed using plates from Silica gel 70 PF 254 (Wako Pure Chemical Industries Ltd.). Compact fluorescent lamp (21 W, product number EFD25ED21AT) was purchased from Mitsubishi Electric Corporation. Literature procedures were used for the preparation of glycine derivatives and silyl enol ethers. 1 3 Preparation of -aryl glycine ester derivatives 1 To a suspension of substituted benzene amine (12.0 mmol) and aac (10.0 mmol) in anhydrous ethanol (3.0 ml) was added alkyl or phenyl bromoacetate (10.0 mmol). The mixture was refluxed overnight under argon gas. Then the resulting mixture was cooled to RT and filtered. The filtrate was evaporated and the residue was purified by column chromatography with hexane/etac mixed solution to afford the desired -aryl glycine ester. General procedure for the Mannich-type reaction between -aryl glycine ester derivatives and silyl enol ether The solution of InBr 3 (7.1 mg, 0.02 mmol), 5-aminofluorescein (3.5 mg, 0.01 mmol) and ethyl p-tolylglycinate (19.3 mg, 0.1 mmol) in THF (5 ml, not anhydrous) was stirred for 30 min at RT at a distance of 5 cm from a 21 W fluorescent lamp. Then 1-Phenyl-1-trimethylsiloxyethylene (45 µl, 0.2 mmol) was added to the reaction

3 mixture. The mixture was stirred for 1 day at RT at a distance of 5 cm from a 21 W fluorescent lamp. The resulting mixture was evapolated. The residue was filtered through a short column of silica gel and eluted with EtAc. The elution was evapolated. The residue was purified by preparative TLC with hexane:etac = 5 : 1 to afford the desired ethyl 4-oxo-4-phenyl-2-(arylamino)butanoate. Figure S1. Reaction apparatus. H Br Br H H 3C CH 3 H 3C H Cl Br H 3C CH 3 CH 3 S xh2 H H Br H H Methylene blue Eosin Y Riboflavin Cl Cl Cl H 2 a Cl I I I a H H H I Rose bengal Fluorescein Figure S2. Structures of organophotoredox catalysts. 5-Aminofluorescein H

4 Table S1. Solvent screening [a] H TMS 10 mol% Ru(bpy) 3 Cl 2 20 mol% InCl 3 Et + solvent, air (1 atm) 21 W fluorescent lamp RT, 1 day H Et 1a 2a 3aa Entry Solvent Yield (%) [b] Hexane Toluene DMF CH 2 Cl 2 EtH THF Water 3 [a] Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), Ru(bpy) 3 Cl 2 (10 mol%), InCl 3 (20 mol%), 21 W fluorescent lamp, solvent (5.0 ml), air (1 atm), RT, 1 day. [b] Yields were determined by MR spectroscopy.

5 Table S2. Investigation of metal complexes in the presence of Ru(bpy) 3 Cl 2 [a] H TMS 10 mol% Ru(bpy) 3 Cl 2 20 mol% metal Et + THF, air (1 atm) 21 W fluorescent lamp RT, 1 day 1a 2a 3aa H Et Entry Metal Yield (%) [b] Entry Metal Yield (%) [b] 1 InCl InCl InBr CuCl In(Tf) icl Bi(Tf) Sc(Tf) Eu(Tf) Ag(Tf) 49 6 ZnCl 2 26 [a] Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), Ru(bpy) 3 Cl 2 (10 mol%), metal (20 mol%), 21 W fluorescent lamp, THF (5.0 ml), air (1 atm), RT, 1 day. [b] Yields were determined by MR spectroscopy.

6 Table S3. Solvent screening in the reaction using a combination of 5-aminofluorescein and InBr 3. [a] H TMS 10 mol% 5-aminofluorescein 20 mol% InBr 3 Et + solvent, air (1 atm) 21 W fluorescent lamp RT, 1 day H Et 1a 2a 3aa Entry Solvent Yield (%) [b] THF CH 2 Cl 2 EtH dioxane 1,2-dimethoxyethane 82 (74) MeC 6 7 [c] THF 74 [a] Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), 5-aminofluorescein (10 mol%), InBr 3 (20 mol%), 21 W fluorescent lamp, solvent (5.0 ml), air (1 atm), RT, 1 day. [b] Yields were determined by MR spectroscopy and the isolated product yields are shown in parentheses. [c] The amount of InBr 3 decreased to 10 mol%.

7 Table S4. Investigation of metal complexes in the presence of 5-aminofluorescein [a] H TMS 10 mol% 5-aminofluorescein 20 mol% metal Et + THF, air (1 atm) 21 W fluorescent lamp RT, 1 day H Et 1a 2a 3aa Entry Metal Yield (%) [b] 1 InBr CuBr AgTf 55 4 [c] CoCl [c] Co(acac) 3 33 [a] Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), 5-aminofluorescein (10 mol%), metal (20 mol%), 21 W fluorescent lamp, THF (5.0 ml), air (1 atm), RT, 1 day. [b] Yields were determined by MR spectroscopy. [c] Reaction with anhydrous THF under an argon atmosphere.

8 Characterization of the product Ethyl 4-oxo-4-phenyl-2-(p-tolylamino)butanoate (3aa) 1 H MR (CDCl 3 ): δ 7.93 (dd, J = 8.1, 1.4 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 6.99 (d, J = 8.1 Hz, 2H), 6.62 (d, J = 8.9 Hz, 2H), 4.58 (br, 1H), 4.37 (br, 1H), 4.18 (q, J = 6.8 Hz, 2H), 3.54 (dd, J = 5.3, 3.4 Hz, 2H), 2.23 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H); 13 C MR (CDCl 3 ): d , , , , , , , , , , 61.60, 53.73, 41.11, 20.54, 14.22; ESI-HRMS calculated for C 19 H 21 3 a [M+a] , found Ethyl 4-oxo-4-phenyl-2-(o-tolylamino)butanoate (3ba) 1 H MR (CDCl 3 ): δ 7.94 (d, J = 8.1 Hz, 2H), 7.58 (t, J = 6.8 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.11 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 6.8 Hz, 1H), 6.69 (dd, J = 8.2, 7.5 Hz, 2H), 4.66 (m, 1H), 4.50 (d, J = 8.1 Hz, 1H), 4.19 (q, J = 7.0 Hz, 2H), 3.62 (dd, J = 17.0, 5.5 Hz, 1H), 3.56 (dd, J = 17.0, 4.8 Hz, 1H), 2.19 (s, 3H), 1.21 (t, J = 7.2 Hz, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , , , 61.71, 53.26, 41.10, 17.61, 14.21; ESI-HRMS calculated for C 19 H 21 3 a [M+a] , found Ethyl 4-oxo-4-phenyl-2-(phenylamino)butanoate (3ca) 1 H MR (CDCl 3 ): δ 7.94 (d, J = 7.5 Hz, 2H), 7.58 (t, J = 7.1 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.18 (t, J = 7.8 Hz, 2H), 6.75 (t, J = 7.4 Hz, 1H), 6.69 (d, J = 7.4 Hz, 2H), 4.62 (br, 1H), 4.53 (br, 1H), 4.19 (q, J = 7.2 Hz, 2H), 3.56 (t, J = 5.1 Hz, 2H), 1.21 (t, J = 7.1 Hz, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 61.68, 53.22, 41.03, 14.21; ESI-HRMS calculated for C 18 H 19 3 a [M+a] , found

9 Ethyl 2-((4-methoxyphenyl)amino)-4-oxo-4-phenylbutanoate (3da) 1 H MR (CDCl 3 ): δ 7.94 (d, J = 7.5 Hz, 2H), 7.58 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 6.77 (d, J = 8.9 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H), 4.53 (t, J = 5.5 Hz, 1H), 4.18 (q, J = 7.0 Hz, 2H), 3.74 (s, 3H), 3.53 (d, J = 5.5 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 61.57, 55.83, 54.65, 41.23, 14.23; ESI-HRMS calculated for C 19 H 21 4 a [M+a] , found Ethyl 2-((4-bromophenyl)amino)-4-oxo-4-phenylbutanoate (3ea) 1 H MR (CDCl 3 ): δ 7.92 (d, J = 8.2 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.25 (d, J = 8.9 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 4.54 (s, 1H), 4.18 (q, J = 7.0 Hz, 2H), 3.54 (d, J = 4.1 Hz, 2H), 1.19 (t, J = 7.1 Hz, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 61.80, 53.17, 40.86, 14.21; ESI-HRMS calculated for C 18 H 18 Br 3 a [M+a] , found Methyl 4-oxo-4-phenyl-2-(p-tolylamino)butanoate (3fa) 1 H MR (CDCl 3 ): δ 7.93 (d, J = 8.2 Hz, 2H), 7.57 (t, J = 6.8 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 6.99 (d, J = 8.1 Hz, 2H), 6.61 (d, J = 7.8 Hz, 2H), 4.60 (s, 1H), 4.37 (d, J = 8.1 Hz, 1H), 3.73 (s, 3H), 3.56 (d, J = 5.5 Hz, 2H), 2.23 (s, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 53.52, 52.61, 41.16, 20.54; ESI-HRMS calculated for C 18 H 19 3 a [M+a] , found tert-butyl 4-oxo-4-phenyl-2-(p-tolylamino)butanoate (3ga) 1 H MR (CDCl 3 ): δ 7.94 (d, J = 8.1 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.1 Hz, 2H), 6.98 (d, J = 7.4 Hz, 2H), 6.61 (d, J = 7.5 Hz, 2H), 4.49 (s, 1H), 4.36 (br, 1H), 3.50 (dd, J = 16.7, 5.8 Hz, 1H), 3.45 (dd, J = 16.6, 5.1 Hz, 1H), 2.22 (s, 3H), 1.38 (s, 9H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 82.12, 54.33, 41.11, 28.02, 20.54; ESI-HRMS calculated for

10 C 21 H 25 3 a [M+a] , found Benzyl 4-oxo-4-phenyl-2-(p-tolylamino)butanoate (3ha) 1 H MR (CDCl 3 ): δ 7.91 (d, J = 8.8 Hz, 2H), 7.56 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.28 (t, J = 3.4 Hz, 3H), 7.22 (m, 2H), 6.98 (d, J = 8.1 Hz, 2H), 6.61 (d, J = 8.1 Hz, 2H), 5.15 (s, 2H), 4.64 (br, 1H), 4.40 (br, 1H), 3.55 (d, J = 5.5 Hz, 2H), 2.23 (s, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , (Two peaks might be overlapped.), , , 67.25, 53.75, 41.12, 20.55; ESI-HRMS calculated for C 24 H 23 3 a [M+a] , found methyl-4-oxo-4-phenyl-2-(p-tolylamino)butanamide (3ia) 1 H MR (CDCl 3 ): δ 7.95 (d, J = 8.2 Hz, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.00 (br, 1H), 7.00 (d, J = 8.2 Hz, 2H), 6.56 (d, J = 8.9 Hz, 2H), 4.55 (s, 1H), 4.29 (d, J = 4.8 Hz, 1H), 3.62 (dd, J = 17.0, 6.1 Hz, 1H), 3.53 (dd, J = 17.3, 4.4 Hz, 1H), 2.82 (d, J = 5.5 Hz, 3H), 2.24 (s, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 55.65, 39.74, 26.35, 20.52; ESI-HRMS calculated for C 18 H a [M+a] , found Methyl 4-(4-methoxyphenyl)-4-oxo-2-(p-tolylamino)butanoate (3fb) 1 H MR (CDCl 3 ): δ 7.91 (d, J = 8.8 Hz, 2H), 6.99 (d, J = Hz, 2H), 6.92 (d, J = 8.9 Hz, 2H), 6.61 (d, J = 8.1 Hz, 2H), 4.58 (br, 1H), 4.48 (br, 1H), 3.87 (s, 3H), 3.72 (s, 3H), 3.51 (d, J = 5.4 Hz, 2H), 2.23 (s, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 55.63, 53.60, 52.56, 40.77, 20.53; ESI-HRMS calculated for C 19 H 21 4 a [M+a] , found

11 Methyl 4-(4-bromophenyl)-4-oxo-2-(p-tolylamino)butanoate (3fc) 1 H MR (CDCl 3 ): δ 7.79 (d, J = 8.1 Hz, 2H), 7.60 (d, J = Hz, 2H), 6.99 (d, J = 8.2 Hz, 2H), 6.60 (d, J = 8.1 Hz, 2H), 4.59 (t, J = 5.1 Hz, 1H), 4.35 (br, 1H), 3.73 (s, 3H), 3.51 (dd, J = 5.1, 3.0 Hz, 2H), 2.23 (s, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 53.51, 52.67, 41.09, 20.55; ESI-HRMS calculated for C 18 H 18 Br 3 a [M+a] , found Ethyl 2-(p-tolylimino)acetate (4a) 1 H MR (CDCl 3 ): δ 8.81 (br, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.1 Hz, 2H), 4.42 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H); 13 C MR (CDCl 3 ): δ , , , , , , 63.83, 21.11, 14.16; ESI-HRMS calculated for C 11 H 14 2 [M+H] , found Ethyl 2-(tetrahydrofuran-2-yl)-2-(p-tolylamino)acetate (5a, Each diastereomer was not determined.) 1 H MR (CDCl 3 ): δ 6.97 (d, J = 8.3 Hz, 2H), 6.61 (d, J = 8.1 Hz, 1H), 6.56 (d, J = 8.1 Hz, 1H), 4.31 (m, 1H), 4.23 (q, J = 6.6 Hz, 1H), 4.20 (m, 2H), 4.04 (m, 1H), 3.94 (dd, J = 14.9, 6.8 Hz, 1H), 3.88 (dd, J = 14.0, 7.1 Hz, 1H), 3.79 (m, 1H), 2.23 (s, 3H), (m, 4H), 1.23 (t, J = 6.8 Hz, 3H); 13 C MR (CDCl 3 ): δ , , , , , , , , , , 80.00, 79.48, 69.37, 68.84, 61.37, 61.28, 61.25, 60.34, 28.52, 28.16, 26.16, 25.72, (Two peaks might be overapped.), 14.37, (The observable signals are reported as a mixture of diastereomers.); ESI-HRMS calculated for C 15 H 22 3 [M+H] , found Reference 1 J. Xie and Z.-Z. Huang, Angew. Chem. Int. Ed. 2010, 49, J. Wang and S. Yang, Tetrahedron Letters, 2016, 57, J. Miguélez, V. R. Batchu and A. Boto, J. rg. Chem. 2012, 77,

12 Copies of 1H MR and 13C MR Spectra of Products H Et

13 Et

14 Et

15 Et

16 Et

17 Et

18 Me H Et

19 Me H Et

20 Br H Et

21 Br H Et

22 Me

23 Me

24

25

26

27

28 HMe

29 HMe

30 Me Me

31 Me Me

32 Me Br

33 Me Br

34 Et

35 Et

36 Et

37 Et