Selective Cleavage of Allyl and Propargyl Ethers to Alcohols Catalyzed by Ti(O-i-Pr) 4 /MX n /Mg

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1 Supporting Information for Selective Cleavage of Allyl and Propargyl Ethers to Alcohols Catalyzed by Ti(O-i-Pr) 4 /MX n /Mg Mutsumi Ohkobo, Sayaka Mochizuki, Takeshi Sano, Yuuki Kawaguchi and Sentaro Okamoto* Department of Applied Chemistry, Kanagawa University, Rokkakubashi, Kanagawa-ku, Yokohama , Japan okamos10@kanagawa-u.ac.jp Index Experimental Procedure General page 2 Preparation of Allyl and Propargyl Ethers and Esters pages 2-3 Stoichiometric Procedure for Deallylation and Depropargylation pages 3-4 Catalytic Procedure for Deallylation and Depropargylation page 4 Catalytic Procedure for Depropargylation in the Presence of AcOEt page 4 Transformation of 5 to 7 pages 4-5 Cyclotrimerization of Alkynes to Substituted Benzenes pages 5 Spectra 1 H and 13 C NMR spectra of Compounds 3c, 3j-Si, 5, 6, 6 and 7 pages 6-18 SI: page - 1 -

2 General. NMR spectra were recorded by use of a solution in CDCl3 at 600 MHz for 1 H and 150 MHz for 13 C, respectively, on JEOL JNM-ECA600 spectrometers. Chemical shifts are reported in parts per million (ppm, δ) relative to Me4Si (δ 0.00), residual CHCl3 (δ 7.26 for 1 H NMR), or a center peak of CDCl3 (δ 77.0 for 13 C NMR). IR spectra were recorded on an FT-IR spectrometer (HITACHI ). All reactions sensitive to oxygen and/or moisture were performed under an argon atmosphere. Dry solvents [tetrahydrofuran (THF), diethyl ether, CH 2 Cl 2 and toluene] were purchased from Kanto Chemical Co., Inc. Mg powder (assay: min. 98.0%) was purchased from Wako Pure Chemical Industries, Ltd. and used as received. Me 3 SiCl and anhydrous MgCl 2 were used as received. A solution of MgBr2 was prepared by the reaction of 1,2-dibromoethane with Mg powder in THF and was stored under an argon atmosphere. Preparation of Allyl and Propargyl Ethers and Esters. The substrate ethers 1, 1 3, and esters were prepared from the corresponding alcohol according to conventional reaction conditions and the following purification by column chromatography. 5 O Si(i-Pr) 3 3c To a solution of 3b (348 mg, 2.00 mmol) in THF (6 ml) was added n-buli (1.50 ml, 1.59 M in hexane, 2.40 mmol) at 0 o C. After being stirred for 1h at 0 o C, (i-pr) 3 SiCl (0.51 ml, 2.40 mmol) was added and the mixture was gradually warmed to room temperature over 1 h. Quinching by addition of water (6 ml) followed by usual extractive work-up and column chromatography yielded 3c (485 mg) in (1) Saino, N.; Kogure, D.; Kase, K.; Okamoto, S. J. Organomet. Chem. 2006, 691, Saino, N.; Amemiya, F.; Tanabe, E.; Kase, K.; Okamoto, S. Org. Lett. 2006, 8, Saino, N.; Kogure, D.; Okamoto, S. Org. Lett. 2005, 7, (2) (a) For allyl ethers, see: Lee, K. Y.; Lee, M. J.; Kim, J. N. Tetrahedron 2005, 61, (b) Ranu, B. C.; Dutta, J.; Guchhait, S. K. J. Org. Chem. 2001, 66, (c) Dunn, J. A.; Pauson, P. L. J. Organomet. Chem. 1991, 419, 383. (d) Schneiderova, L.; Strouf, O.; Gruner, B.; Pouzar, V.; Drasar, P.; Hampl, R.; Kimlova, I. Collect. Czec. Chem. Commun. 1992, 57, 463. (e) Ashim, R.; Sahabuddin, S.; Basudeb, A.; Sukhendu, B. M. Tetrahedron 2005, 61, 365. (3) For propargyl ethers, see: (a) Gozzo, F. C.; Fernandes, S. A.; Rodrigues, D. C.; Eberlin, M. N.; Marsaioli, A. J. J. Org. Chem. 2003, 68, (b) Haight, A. R.; Stoner, E. J.; Peterson, M. J.; Grover, V. K. J. Org. Chem. 2003, 68, (c) Bartoli, G.; Cupone, G.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Marcantoni, E.; Procopio, A. Synlett 2001, (d) Bailey, W. F.; England, M. D.; Mealy, M. J.; Thongsornkleeb, C.; Teng, L. Org. Lett. 2000, 2, 489. (e) Taniguchi, T.; Ogasawara, K. Angew. Chem., Int. Ed. 1998, 37, (4) (a) Iwasaki, F.; Koyanagi, S.; Tsucha, S. Jpn. Kokai Tokkyo Koho, , 13 Dec (b) Genet, J. P.; Blart, E.; Savignac, M.; Lemeune, S.; Lemaire-Audoire, S.; Paris, J. M.; Bernard, J. Tetrahedron 1994, 50, 497. See also ref 3d. (5) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; Wiley: New York, SI: page - 2 -

3 73% yield: 1 H NMR (CDCl 3, 600 MHz) δ (m, 5H, Ph), 4.19 (s, 2H, OCH 2 C C), 3.57 (t, J=6.0 Hz, OCH 2 CH 2 ), 2.70 (t, J=7.8 Hz, 2H, PhCH 2 ), (m, 2H, OCH 2 CH 2 ), (m, 21H, Si(i-Pr) 3 ); 13 C NMR (CDCl 3, 125 MHz) δ , , , , , 87.28, 68.87, 58.79, 32.40, 31.19, 18.56, 11.14; IR (neat) cm -1 : 2941, 2889, 2864, 2060, 1496, 1454, 1350, 1103, 744, 698, 578; Anal. Calcd for C 21 H 3 OSi; C, 76.30; H, 10.37; Found C, 76.02; H, C 6 H 13 H H H O Me 3 Si 3j-Si To a solution of 3j (640 mg, 1.52 mmol) in THF (6 ml) was added EtMgBr (1.74 ml, 1.05 M in THF, 1.82 mmol) at 0 o C. After being stirred for 1h at 0 o C, Me 3 SiCl (0.23 ml, 1.82 mmol) was added and the mixture was gradually warmed to room temperature over 1 h. Quinching by addition of water (6 ml) followed by usual extractive work-up and column chromatography yielded 3c (765 mg) in 100% yield; 1 H NMR (CDCl 3, 600 MHz) δ 5.35 (br, 1H, CH=C), 4.18 (s, 2H, OCH 2 C C), (m, 1H, OCH), 2.39 (d, J=12.0 Hz, 1H, CH 2 C=C), 2.23 (t, J=12.0 Hz, 1H, CH 2 C=C), (m, 5H), (m, 11H), (m, 10H), 1.00 (s, 3H, CH 3 ), 0.91 (d, J=6.0 Hz, 3H, CHCH 3 ), (m, 6H, CH(CH 3 ) 2 ), 0.68 (s, 3H, CH 3 ), 0.17 (s, 9H, Si(CH 3 ) 3 ); 13 C NMR (CDCl 3, 150 MHz) δ , , , 90.47, 78.56, 56.76, 56.15, 50.14, 42.31, 39.77, 39.50, 38.83, 37.17, 36.81, 36.18, 35.78, 31.94, 31.87, 28.22, 28.17, 27.99, 24.28, 23.82, 22.81, 22.55, 21.05, 19.33, 18.70, 11.84, -0.17; IR (KBr) cm -1 : 2953, 2935, 2899, 2866, 2852, 2173, 1460, 1450, 1381, 1249, 1093, 844; Anal. Calcd for C 33 H 56 O; C, 79.77; H, 11.36; Found C, 79.75; H, Stoichiometric Procedure for Deallylation and Depropargylation. To a mixture of the substrate ether (1.0 mmol), Ti(O-i-Pr) 4 (294 µl, 1.0 mmol), Mg powder (48.6 mg, 2.0 mmol) and THF (5 ml) was added Me 3 SiCl (0.13 ml, 1.0 mmol) and the mixture was stirred at room temperature. After confirming the consumption of the substrate by TLC analysis, the mixture was treated according to the following work-up procedures. The spectroscopic data and TLC analysis of the resulting product confirmed that structure was identical to that of the parent alcohol. Work-up procedure A (Acidic work-up): For the product sensitive to basic conditions, to the reaction mixture was added aq. 1M HCl (5 ml) and the resulting mixture was extracted with ether (or AcOEt). The combined organic layers were washed with brine, dried over MgSO 4, concentrated and purified by column chromatography on silica gel (hexane-ether or AcOEt) to afford the corresponding alcohol. Work-up procedure B (Basic work-up): For the acid-sensitive product such as those having a acetal or ketal group(s), to the reaction mixture were added sat. aq. NaHCO 3 (0.3 ml), NaF (~1 g) and Celite (~1 g) and the resulting mixture was filtered through a pad of Celite with ether. The filtrate was SI: page - 3 -

4 concentrated and chromatographed on silica gel to give the corresponding alcohol. Catalytic Procedure for Deallylation and Depropargylation. To a mixture of the substrate ether (1.0 mmol), Ti(O-i-Pr) 4 (14.7 µl, 0.05 mmol), Mg powder (48.6 mg, 2.0 mmol) and THF (2 ml) was added Me 3 SiCl (0.15 mmol) or MgBr 4 (0.15 mmol, 1.0 M in THF) and the mixture was stirred at room temperature. After confirming the consumption of the substrate by TLC analysis, the mixture was treated according to the work-up procedure A or B mentioned above. The spectroscopic data and TLC analysis of the resulting product confirmed that structure was identical to that of the parent alcohol. Catalytic Procedure for Depropargylation in the Presence of AcOEt. To a mixture of the substrate propargyl ether (1.0 mmol), Ti(O-i-Pr) 4 (294 µl, 1.0 mmol), AcOEt (0.20 ml, 2.0 mmol), Mg powder (48.6 mg, 2.0 mmol) and THF (5 ml) was added Me 3 SiCl (0.13 ml, 1.0 mmol) and the mixture was stirred at room temperature. After confirming the consumption of the substrate by TLC analysis, the mixture was treated according to the work-up procedure A or B mentioned above. The spectroscopic data and TLC analysis of the resulting product confirmed that structure was identical to that of the parent alcohol. Transformation of 5 to 7. O OR OBn O 5 6 (R = H) 6' (R = Bn) O OH 7 To a mixture of 5 (188 mg, 1.0 mmol), Ti(O-i-Pr) 4 (294 µl, 1.0 mmol), AcOEt (0.20 ml, 2.0 mmol), Mg powder (48.6 mg, 2.0 mmol) and THF (5 ml) was added Me 3 SiCl (0.13 ml, 1.0 mmol) and the mixture was stirred for 26 h at room temperature. To this wes added aq. 1M HCl (5 ml) and the resulting mixture was extracted with ether. The combined organic layers were washed with brine, dried over MgSO 4 and filtered through a pad of Celite with ether. The filtrate was concentrated and chromatographed on silica gel to give the corresponding alcohol 6 (136 mg) in 91 % yield. To a mixture of 6 (122 mg, 0.81 mmol), BnBr (0.12 ml, 0.97 mmol), K 2 CO 3 (560 mg, 4.05 mmol) and CH 3 CN (3 ml) was stirred for 4 h at 85 o C to provide benzyl ether 6 (181 mg) in 93 % yield. To a mixture of 6 (240 mg, 1.0 mmol), Ti(O-i-Pr) 4 (14.7 µl, 0.05 mmol), Mg powder (48.6 mg, 2.0 mmol) and THF (2 ml) was added Me 3 SiCl (0.02mL, 0.15 mmol) and the mixture was stirred for 4 h at room temperature. To this was added aq. 1M HCl (5 ml) and the resulting mixture was extracted with ether. The combined organic layers were washed with brine, dried over MgSO 4 and filtered through a pad of Celite with ether. The filtrate was concentrated and chromatographed on silica gel to give the corresponding alcohol 7 (200 mg) in 100 % yield. SI: page - 4 -

5 O O 5 3d 1 H NMR (CDCl 3, 600 MHz) δ 6.91 (d, J=8.4 Hz, 2H, Ph), 6.86 (d, J=9.0 Hz, 2H, Ph), 6.04 (ddt, J=4.8, 10.2, 17.4 Hz, 1H, CH=C), 5.26 (dd, J=1.8, 17.4 Hz, 1H, CH 2 =C), 5.27 (dd, J=1.8, 10.2 Hz, 1H, CH 2 =C), 4.63 (d, J=3.0 Hz, 2H, OCH 2 C C), 4.49 (d, J=4.8 Hz, 2H, OCH 2 C=C), 2.50 (t, J=2.4H, 1H, C CH); 13 C NMR (CDCl 3, 150 MHz) δ , , , , , , 78.86, 75.28, 69.39, OH O 6 3d 1 H NMR (CDCl 3, 600 MHz) δ 6.80 (d, J=9.0 Hz, 2H, Ph), 6.75 (d, J=8.4 Hz, 2H, Ph), 6.04 (ddt, J=5.4, 10.2, 17.4 Hz, 1H, CH=C), 4.54 (br, 1H, OH), 5.39 (dd, J=1.2, 17.4 Hz, 1H, CH 2 =C), 5.27 (dd, J=1.2, 10.2 Hz, 1H, CH 2 =C), 4.48 (dd, J=1.2 Hz, 5.4 Hz, 2H, OCH 2 ); 13 C NMR (CDCl 3, 150MHz) δ , , , , , , OBn O 6 3b 1 H NMR (CDCl 3, 600 MHz) δ 7.42 (d, J=7.8 Hz, 2H, Ph), 7.38 (t, J=7.2 Hz, 2H, Ph), 7.32 (t, J=7.2, 1H, Ph), 6.90 (d, J=9.6 Hz, 2H, C 6 H 4 O), 6.85 (d, J=8.4 Hz, 2H, C 6 H 4 O), 6.04 (ddt, J= 5.4, 10.2, 16.8 Hz, 1H, CH=C), 5.39 (dd, J=1.2, 16.8 Hz, 1H, CH 2 =C), 5.27 (dd, J=1.2, 10.2 Hz, 1H, CH 2 =C), 5.01 (s, 2H, OCH 2 Ph), 4.49 (dd, J=1.2 Hz, 5.4Hz, 2H, OCH 2 ); 13 C NMR (CDCl 3, 150 MHz) δ , , , , , , , , , , 70.63, OBn OH 7 3b 1 H NMR (CDCl 3, 600 MHz) δ 7.42 (d, J=7.8 Hz, 2H, Ph), 7.37 (t, J=7.8 Hz, 2H, Ph), 7.31 (t, J=7.2, 1H, Ph), 6.85 (d, J=9.0 Hz, 2H, C 6 H 4 O), 6.75 (d, J=8.4 Hz, 2H, C 6 H 4 O), 5.00 (s, 2H, OCH 2 ), 4.60 (br, 1H, OH); 13 C NMR (CDCl 3, 150 MHz) δ , , , , , , , , SI: page - 5 -

6 Low Valent Titanium-Mediated Cyclotrimerization of Alkynes to Substituted Benzenes. To a mixture of the substrate alkynes (1.0 mmol), Ti(O-i-Pr) 4 (59 or 294 µl, 0.20 or 1.0 mmol, respectively), Mg powder (73 mg, 3.0 mmol) and THF (10 ml) was added Me 3 SiCl (0.26 ml, 2.0 mmol) and the mixture was stirred at room temperature. After confirming the consumption of the substrate by TLC analysis, to the reaction mixture were added sat. aq. NaHCO 3 (0.3 ml), NaF (~1 g) and Celite (~1 g) and the resulting mixture was filtered through a pad of Celite with ether. The filtrate was concentrated and chromatographed on silica gel to give the corresponding benzene derivative(s). The resulting benzene derivatives 2a-d were identical to the authentic samples prepared previously by us. 1 SI: page - 6 -

7 1 H NMR (CDCl 3, 600 MHz) of 3c SI: page - 7 -

8 13 C NMR (CDCl 3, 150 MHz) of 3c SI: page - 8 -

9 1 H NMR (CDCl 3, 600 MHz) of 3j-Si SI: page - 9 -

10 13 C NMR (CDCl 3, 150 MHz) of 3j-Si SI: page

11 1 H NMR (CDCl 3, 600 MHz) of 5 SI: page

12 13 C NMR (CDCl 3, 150 MHz) of 5 SI: page

13 1 H NMR (CDCl 3, 600 MHz) of 6 SI: page

14 13 C NMR (CDCl 3, 150 MHz) of 6 SI: page

15 1 H NMR (CDCl 3, 600 MHz) of 6 SI: page

16 13 C NMR (CDCl 3, 150 MHz) of 6 SI: page

17 1 H NMR (CDCl 3, 600 MHz) of 7 SI: page

18 13 C NMR (CDCl 3, 150 MHz) of 7 SI: page

Brønsted Base-Catalyzed Reductive Cyclization of Alkynyl. α-iminoesters through Auto-Tandem Catalysis

Supporting Information Brønsted Base-Catalyzed Reductive Cyclization of Alkynyl α-iminoesters through Auto-Tandem Catalysis Azusa Kondoh, b and Masahiro Terada* a a Department of Chemistry, Graduate School