On the use of phosphoramidite ligands in copper-catalyzed asymmetric transformations with trialkylaluminum reagents

Transcription

1 Supporting information for n the use of phosphoramidite ligands in copper-catalyzed asymmetric transformations with trialkylaluminum reagents Chloée Bournaud, Caroline Falciola, Thomas Lecourt, Stéphane Rosset, Alexandre Alexakis * and Laurent Micouin * Laboratoire de Chimie Thérapeutique, UMR 8638 associée au CRS et à l'université René Descartes, Faculté des Sciences armaceutiques et Biologiques, 4 av de l'bservatoire, Paris cedex 06 (France) and Department of rganic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland laurent.micouin@univ-paris5.fr; alexandre.alexakis@chiorg.unige.ch Table of Contents General methods: S2 Experimental data: S2-S7 Copy of spectra: S8-S39 S1

2 General methods Silica gel ( mesh) was used for product purification by flash column chromatography. Solvents were purified and dried by standard techniques, and distilled prior to use. All organic extracts were dried over MgS 4 or a 2 S 4. 1 H, 13 C and 31 P MR spectra were recorded on a 300 or 400 MHz spectrometer (H value). Trimethyl- and triethylaluminum solutions were purchased by Aldrich Company and used as such. Compounds 1 and 3 were prepared according to reported procedures. 1 osphoramidites 5 and 9a-d were prepared according to reported procedures. 2 General procedure for the preparation of dimethylaminophosphine ligands. General remark: Dimethylaminophosphine are air sensitive reagents that readily oxidize, and must be used rapidly after isolation. (S,S)-bis-(1-phenyl-ethyl)-aminodimethylphosphine 7 A flame-dried schlenk tube was charged with phosphoramidite ligand 9a (50 mg, 0.11 mmol) in anhydrous CH 2 Cl 2 (5 ml), trimethylaluminum (250 µl, 2M in hexanes, 0.5 mmol) was added and the reaction mixture was stirred at room temperature for 20 min. The reaction mixture was filtered through basic alumina. rganic solvent was removed and the crude was dissolved in cyclohexane (4 ml) and washed with an aqueous solution of Rochelle s salt (4 1 a) Moore, J. A.; Muth, R.; Sorace S. J. rg. Chem. 1974, 39, b) Contreras, F. G.; Lora-Tamayo, M.; Sanz, A. Heterocycles 1989, 28, a) Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim C. Synlett 2001, 9, b) Alexakis, A.; Polet, D.; Benhaim, C.; Rosset S. Tetrahedron : Asymmetry 2004, 15, c) Monti, C.; Gennari, C.; Piarulli U. Tetrahedron. Lett. 2004, 45, S2

3 ml). The aqueous phase was extracted with cyclohexane (2 x 4 ml). rganic layers were dried over a 2 S 4, the solvent was evaporated to give pure 7 (23 mg, 0.08 mmol). 1 H MR (300 MHz, CDCl 3 ) δ (m, 6H), (m, 4H), 4.39 (q, J = 7.0 Hz, 1H), 4.35 (q, J = 7.0 Hz, 1H), 1.62 (d, J = 7.0 Hz, 6H), 1.27 (d, J = 6.0 Hz, 3H), 1.17 (d, J = 6.0 Hz, 3H) ; 13 C (CDCl 3, 75 MHz) δ 144.5, 127.8, 127.7, 126.2, 53.1, 53.0, 21.3, 21.2, 17.5 (d, J = 19.0 Hz), 16.9 (d, J = 14.5 Hz); 31 P MR (122MHz, CDCl 3 ) δ 12.9 ; MS (ES+, a) 286 (MH + ). (S,S)-bis-(1-phenyl-ethyl)-aminodimethylphosphine oxide 6 1 H MR (300 MHz, CDCl 3 ) δ (m, 10H), 4.86 (q, J = 7.5 Hz, 1H), 4.80 (q, J = 7.5 Hz, 1H), 1.77 (d, J = 7.5 Hz, 6H), 1.40 (d, J = 12.5 Hz, 3H), 1.25 (d, J = 13.5 Hz, 3H) ; 13 C (CDCl 3, 75 MHz) δ 142.4, 128.2, 127.8, 127.2, 52.2, 52.1, 20.2, 20.0, 19.0 (d, J = 20 Hz), 18.0; 31 P MR (122MHz, CDCl 3 ) δ 42.8 ; MS (ES+, a) 324 (Ma + ). (R,R)-bis-(1-phenyl-propyl)-aminodimethylphosphine 10b A flame-dried schlenk tube was charged with phosphoramidite ligand (R,R)-9b (56 mg, 0.12 mmol) in anhydrous CH 2 Cl 2 (5 ml), trimethylaluminum (260 µl, 2M in hexanes, 0.52 mmol) was added the reaction mixture was stirred at room temperature for 20 min. The reaction mixture was filtered through basic alumina. rganic solvent was removed and the crude was dissolved in cyclohexane (4 ml) and washed with an aqueous solution of Rochelle s salt (4 ml). The aqueous phase was extracted with cyclohexane ( 2 x 4 ml). rganic layers were dried over a 2 S 4, the solvent was evaporated to give pure (R,R)-10b (25 mg, mmol). 1 H MR (300 MHz, CDCl 3 ) δ (m, 6H), (m, 4H), (m, 2H), (m, 2H), (m, 2H), 1.29 (d, J = 6.5 Hz, 3 H), 1.15 (d, J = 6.0 Hz, 3 H), 0.89 (t, J S3

4 = 7.0 Hz, 6 H) ; 13 C (CDCl 3, 75 MHz) δ 142.6, 128.4, 127.6, 126.0, 60.7, 28.1, 28.0, 17.7 (d, J = 16.5 Hz), 17.5 (d, J = 18.0 Hz), 11.8 ; 31 P MR (122 MHz, CDCl 3 ) δ (S,S)-bis-(1-naphthalen-1-yl-ethyl)-aminodimethylphosphine 10c A flame-dried schlenk tube was charged with phosphoramidite ligand (S,S)-9c (43 mg, mmol) in anhydrous CH 2 Cl 2 (4 ml), trimethylaluminum (180 µl, 2M in hexanes, 0.36 mmol) was added the reaction mixture was stirred at room temperature for 20 min. The reaction mixture was filtered through basic alumina. rganic solvent was removed and the crude was dissolved in cyclohexane (4 ml) and washed with an aqueous solution of Rochelle s salt (4 ml). The aqueous phase was extracted with cyclohexane ( 2 x 4 ml). rganic layers were dried over a 2 S 4, the solvent was evaporated to give pure (S,S)-10c (22 mg, mmol). 1 H MR (300 MHz, CDCl 3 ) δ 7.87 (d, J = 8.5 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 7.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 7.0 Hz, 2H), 7.31 (t, J = 8.5 Hz, 2H), 7.10 (t, J = 7.5 Hz, 2H), 5.41 (q, J = 7.0 Hz, 1H), 5.36 (q, J = 7.0 Hz, 1H), 1.81 (d, J = 7.0 Hz, 6H), 1.39 (d, J = 7.0 Hz, 3H), 1.31 (d, J = 6.5 Hz, 3H) ; 13 C (CDCl 3, 75 MHz) δ 140.8, 133.4, 130.9, 128.6, 126.9, 125.2, 125.0, 124.9, 124.7, 123.3, 53.5, 53.4, 23.2, 23.0, 18.5 (d, J = 20.0 Hz), 17.0 (d, J = 14.0 Hz) ; 31 P MR (122 MHz, CDCl 3 ) δ (R,R)-bis-(1-naphthalen-2-yl-ethyl)-aminodimethylphosphine 10d A flame-dried schlenk tube was charged with phosphoramidite ligand (R,R)-9d (44 mg, mmol) in anhydrous CH 2 Cl 2 (4 ml), trimethylaluminum (190 µl, 2M in hexanes, 0.38 mmol) was added the reaction mixture was stirred at room temperature for 20 min. The reaction mixture was filtered through basic alumina. rganic solvent was removed and the crude was dissolved in cyclohexane (4 ml) and washed with an aqueous solution of Rochelle s salt (4 S4

5 ml). The aqueous phase was extracted with cyclohexane ( 2 x 4 ml). rganic layers were dried over a 2 S 4, the solvent was evaporated to give pure (R,R)-10d (18 mg, mmol). 1 H MR (300 MHz, CDCl 3 ) δ (m, 2H), (m, 4H), (m, 6H), 7.15 (dd, J = 8.5 Hz et J = 1.0 Hz, 2H), 4.57 (q, J = 7.0 Hz, 1H), 4.53 (q, J = 7.0 Hz, 1H), 1.77 (d, J = 7.0 Hz, 6H), 1.34 (d, J = 6.0 Hz, 3H), 1.22 (d, J = 6.0 Hz, 3H) ; 13 C (CDCl 3, 75 MHz) δ 141.9, 133.0, 132.2, 127.9, 127.3, 127.2, 125.8, 125.6; 125.4, 53.3, 53.2, 21.3, 21.2, 17.2 (d, J = 19.0 Hz), 17.0 (d, J = 14.0 Hz); 31 P MR (122 MHz, CDCl 3 ) δ General procedure for the copper dimethylphosphoramine catalyzed ring opening of bicyclic hydrazines 1 and 3 with organoaluminum 1-[2-methyl-3-cyclopenten-1-yl]-4-phenyl-1,2,4-triazolidin-3,5-dione 2a A flame-dried schlenk tube was charged with Cu(Tf) 2 (5.5 mg, mmol) and ligand 7 (8.6 mg, mmol) in ahnydrous CH 2 Cl 2 (2 ml), the reaction mixture was stirred at room temperature for 40 min. The solution was cooled to 0 C, bicyclic hydrazine 1 (120 mg, 0.5 mmol) dissolved in CH 2 Cl 2 (2 ml) and trimethylaluminum (1 ml, 2 M in hexanes, 2 mmol) were added. The reaction was quenched after 4 hours with aqueous HCl and extracted with ether. The crude was purified by flash chromatography (elution conditions: cyclohexane/etac 80/20) to afford compound 2a (110 mg, 0.43 mmol). Spectral data are in accordance with the previous description of 2a. 3 1 H MR (300 MHz, CDCl 3 ) δ (br s, 1H), (m, 5H), 5.61 (br s, 2H), (m, 1H), (m, 2H), (m, 1H), 1.13 (d, J = 7.0 Hz, 3H); 13 C (CDCl 3, 75 MHz) δ 153.8, 152.2, 135.0, 131.3, 129.1, 128.2, 127.4, 125.6, 62.5, 43.4, 35.1, M. Pineschi, F. Del Moro, P. Crotti, F. Macchia rg. Lett. 2005, 7, S5

6 Ee was measured by chiral BERGER SFC (Chiralcel AD column, 10 % H during 2 min, then 1 %/min until 25 % H; 2 ml/min; 200 bar t R1 = 7.42, t R2 = 12.00) 2-[2-methyl-3-cyclopenten-1-yl]-2,3-dihydrophtlalazin-1,4-dione 4a A flame-dried schlenk tube was charged with Cu(Tf) 2 (5.5 mg, mmol) and ligand 7 (10 mg, mmol) in anhydrous CH 2 Cl 2 (1 ml), the reaction mixture was stirred at room temperature for 40 min. The solution was cooled to 0 C, bicyclic hydrazine 3 (113 mg, 0.5 mmol) dissolved in CH 2 Cl 2 (4 ml) and trimethylaluminum (1 ml, 2 M in hexanes, 2 mmol) were added. The reaction was quenched after 4 hours with aqueous HCl and extracted with ether. The crude was purified by flash chromatography (elution conditions: cyclohexane/etac 90/10) to afford compound 4a (114 mg, 0.43 mmol). Spectral data are in accordance with the previous description of 4a. 3 1 H MR (400 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), (m, 2H), (m, 2H), 5.43 (overlapping dt, J = 9.0 Hz and J = 7.0 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 1.07 (d, J = 7.0 Hz, 3H) ; 13 C (CDCl 3, 100 MHz) δ 158.8, 151.9, 135.2, 133.0, 132.6, 129.4, 127.6, 124.8, 62.9, 44.8, 37.0, Ee was measured by chiral BERGER SFC (Chiralcel D-H column, 5 % H during 8 min, then 1 %/min until 25 % H; 2 ml/min; 200 bar t R1 = 9.0, t R2 = 9.6) 1-[2-ethyl-3-cyclopenten-1-yl]-4-phenyl-1,2,4-triazolidin-3,5-dione 2b A flame-dried schlenk tube was charged with Cu(Tf) 2 (5.5 mg, mmol) and ligand 7 (8.6 mg, mmol) in anhydrous CH 2 Cl 2 (1 ml), the reaction mixture was stirred at room temperature for 40 min. The solution was cooled to 0 C, bicyclic hydrazine 1 (120 mg, 0.5 mmol) dissolved in CH 2 Cl 2 (1 ml) and triethylaluminum (0.39 ml, 1.9 M in toluene, 0.74 mmol) were added. The reaction was quenched after 16 hours with aqueous HCl and extracted S6

7 with ether. The crude was purified by flash chromatography (elution conditions: cyclohexane/etac 90/10) to afford compound 2b (77 mg, 0.28 mmol). Spectral data are in accordance with the previous description of 2b. 3 1 H MR (300 MHz, CDCl 3 ) δ (br s, 1H), (m, 5H), 5.70 (br s, 2H), (m, 1H), (m, 2H), (m, 1H), (m, 2H), 0.96 (t, J = 7.5 Hz, 3H) ; 13 C (CDCl 3, 75 MHz) δ 153.7, 151.9, 133.2, 131.3, 129.1, 128.1, 125.5, 60.0, 50.8, 35.6, 26.6, Ee was measured by chiral BERGER SFC (Chiralcel J-H column, 10 % H during 2 min, then 1 %/min until 25 % H; 2 ml/min; 200 bar t R1 = 3.4, t R2 = 4.3) 2-[2-ethyl-3-cyclopenten-1-yl]-2,3-dihydrophtlalazin-1,4-dione 4b A flame-dried schlenk tube was charged with Cu(Tf) 2 (5.5 mg, mmol) and ligand 7 (8.6 mg, mmol) in anhydrous CH 2 Cl 2 (1 ml), the reaction mixture was stirred at room temperature for 40 min. The solution was cooled to 0 C, bicyclic hydrazine 3 (113 mg, 0.5 mmol) dissolved in CH 2 Cl 2 (4 ml) and triethylaluminum (0.8 ml, 1.9 M in toluene, 1.52 mmol) was added. The reaction was quenched after 4 hours with aqueous HCl and extracted with ether. The crude was purified by flash chromatography (elution conditions: cyclohexane/etac 80/20) to afford compound 4b (8 mg, mmol). Spectral data are in accordance with the previous description of 4b. 3 1 H MR (400 MHz, CDCl 3 ) δ (m, 1H), (m, 1H), (m, 2H), (m, 3H), (m, 2H), 2.55 (dd, J = 16.0 Hz and J = 6.0 Hz, 1H), (m, 2H), 0.90 (t, J = 7.5 Hz, 3H) ; 13 C (CDCl 3, 100 MHz) δ 157.9, 152.0, 133.4, 132.9, 132.6, 129.4, 128.3, 127.7, 124.8, 60.0, 52.1, 37.3, 27.0, Ee was measured by chiral BERGER SFC (Chiralcel B-H column, 5 % H during 2 min, then 1 %/min until 15 % H; 2 ml/min; 200 bar t R1 = 4.5, t R2 = 5.2) S7

8 S8

9 H 2a S9

10 H 2a S10

11 Et H 2b S11

12 Et H 2b S12

13 H 4a S13

14 H 4a S14

15 H 4a S15

16 Et H 4b S16

17 Et H 4b S17

18 P 5 S18

19 P 5 S19

20 P + Al (2M in heptane) in CH 2 Cl 2 5 S20

21 P 6 S21

22 P 6 S22

23 P 6 S23

24 P 6 S24

25 P 7 S25

26 P 7 S26

27 P 7 S27

28 P 7 S28

29 P 10b Et Et S29

30 P 10b Et Et S30

31 P 10b Et Et S31

32 P 10b Et Et S32

33 P 10c S33

34 P 10c S34

35 P 10c S35

36 P 10c S36

37 P 10d S37

38 P 10d S38

39 P 10d S39

40 P 10d S40