Catalytic Conjugate Additions of Nitrogen, Phosphorus, and Carbon-containing Nucleophiles. by Amphoteric Vanadyl Triflate

Transcription

1 Catalytic Conjugate Additions of Nitrogen, Phosphorus, and Carbon-containing Nucleophiles by Amphoteric Vanadyl Triflate S1 Yow-Dzer Lin, Jun-Qi Kao, and Chien-Tien Chen* Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan, RC Spectral data and characterization for products 1a -e, 3a -3h, and 4a,b -5a,b are included (54 pages). SUPPRTING INFRMATIN General S2 General procedure for the preparation of vanadyl triflate s2 General workup procedure for the conjugate additions s3 General procedure for the conjugate additions of carbamates, amides, sulfonamides to α,β-unsaturated carbonyls (aza-michael Reaction) S3 General procedure for the conjugate additions of phosphines and phosphites to α,β-unsaturated carbonyls (phospha-michael Reaction) S3-S4 General procedure for the Friedel-Crafts-type Michael Reactions S4 Analytical data of products 1a -e, 3a -3h, and 4a,b -5a,b S4-S10 References for known compounds s10 1 H, 13 C, and 31 P NMR spectra of products 1a -e, 3a -3h, and 4a,b -5a,b S11-S54

2 S2 General. 1 H, 13 C, 31 P NMR spectra were recorded on a Bruker Avance-400 spectrometer. Chemical shifts (δ), reported in ppm, for 1 H NMR (400 MHz) are relative to the singlet at δ 7.26 ppm for chloroform, for 13 C NMR (100 MHz) are relative to the triplet at δ 77.0 ppm for CDCl 3 as an internal reference, and for 31 P NMR (162 MHz) are relative to the singlet at δ 0.0 ppm for 85% H 3 P 4 as an internal reference. Coupling constants (J) are reported in Hz. Mass spectra were recorded on a Finnigan TCQ-700 spectrometer with ionization voltages of 70 or 20 ev unless otherwise stated. Data are reported in the form m/e (intensity relative to base = 100%). Elemental analyses were measured with a Heraeus CHN-S Rapid or an Elementar Vario EL III (CSIST) instrument. Analytical TLC was performed on Merck silica gel plates with QF-254 indicator. Visualization was accomplished with UV light, phosphomolybdic acid (PMA), and KMn 4. Column (flash) chromatography was performed using μm silica gel. Solvents for extraction and chromatography were reagent grade. Dichloromethane and acetonitrile were dried over CaH 2 under nitrogen atmosphere before use. All reactions were run under nitrogen and the end products were isolated as chromatographically pure materials. The VX 2 series of compounds (brand name as Clip-all series, US patent # 6,541,659 B1, 2003) is now available directly from National Taiwan Normal University ( chefv043@ntnu.edu.tw). General procedure for the preparation of vanadyl triflate-v(tf) 2 To a 50-mL, two-necked, round-bottomed flask was added vanadyl sulfate, VS 4 (2.1 mmol, 342 mg) followed by addition of MeH (2 ml). To the methanolic solution of vanadyl sulfate, was slowly added a solution of Ba(Tf) 2 (872 mg, 2.0 mmol) in MeH (2 ml) at ambient temperature. After having been stirred for 30 min, the reaction mixture contains copious amount of barium sulfate precipitate, which was filtered off by passing through a short pad of dry Celite. The filtrate was concentrated to give faint blue solid which was further dried at 120 o C for 4 hours under vacuum to furnish 622 mg (85%) of vanadyl triflate. It can be stored at ambient temperature in dry cabinet and can be used directly for catalytic reactions.

3 S3 General workup procedure for the conjugate additions with solvent (GWP-1 Procedure) After completion of a given conjugate addition reaction (as monitored by TLC), the resulting reaction mixture was concentrated under reduced pressure and the resulting residue was purified by column chromatography on silica gel by elution with EtAc/hexanes to give the corresponding isolated, purified product. General workup procedure for the conjugate additions in neat conditions (GWP-2 Procedure) After completion of a given conjugate addition reaction (as monitored by TLC), the resulting reaction mixture was diluted with a minimum amount of CH 2 Cl 2. And, the mixture was purified by column chromatography on silica gel by elution first with hexanes (40 ml) and then with EtAc/hexanes to give the corresponding isolated, purified product. General procedure for the conjugate additions of carbamates, amides, and sulfonamides to α,β-unsaturated carbonyl compoundss (aza-michael Reaction) To a 10-mL, round-bottomed flask was placed V(Tf) 2 (5-10 mol%), a given α,β-unsaturated carbonyl compound (2.0 mmol) in CH 3 CN/CH 2 Cl 2 (0.5, 2.0 M, or neat for amides). A given nitrogen-centered nucleophile ( equiv) was then added. The reaction mixture was stirred at ambient temperature or heated (at 70 o C for amides) for an appropriate reaction time (see Table 2). The reaction mixture was then worked up with the GWP-2 procedure for amides or with the GWP-1 procedure for other N-centered nucleophiles. General procedure for the conjugate additions of phosphines or phosphites to α,β-unsaturated carbonyl compounds (phospha-michael Reaction) For phosphines. To a 10-mL, round-bottomed flask was placed V(Tf) 2 (10 mol%), acrylonitrile (8.0 equiv), and diphenylphosphine (2.0 mmol). After having been stirred at ambient temperature for 24 h under neat conditions, the mixture was treated with another portion of acrylonitrile (2.0 equiv) and stirred for another 8 h. The resulting reaction mixture was then worked

4 S4 up with the GWP-1 procedure. For phosphites. To a 10-mL, round-bottomed flask was placed V(Tf) 2 (5 mol%) in Ac 2 (2.6 mmol, 1.3 equiv). The mixture was stirred at ambient temperature for 10 min and then treated with a phosphite (2.4 mmol, 1.2 equiv) for another 10 min. After addition of a given α,β-unsaturated carbonyl compound (2.0 mmol), the mixture was stirred at ambient temperature or 70 o C under neat condition for an appropriate reaction time (see Table 4). The resulting reaction mixture was then worked up with the GWP-2 procedure. General procedure for the Friedel-Crafts-type Michael Reaction To a 10-mL, round-bottomed flask was placed V(Tf) 2 (10 mol%) and a given α,β-unsaturated carbonyl compound (2.0 mmol) in CH 2 Cl 2 (2.0 ml). A C-centered nucleophile (3.0 mmol, 1.5 equiv) was then added. The reaction mixture was stirred at ambient temperature for an appropriate reaction time (see, Table 5) and then worked up with the GWP-1 procedure. Analytical data of products 1a -e, 3a -3h, and 4a,b -5a,b Ethyl (1-Methyl-3-oxo-3-phenyl-propyl)-carbamate (1a ) 1 H NMR (400 MHz, CDCl 3 ) δ 7.96 (d, J = 7.4, 2H), 7.57 (t, J = 7.4, 1H), HN CH 2 CH (t, J = 7.4, 2H), 5.19 (brs, 1H), (m, 1H), 4.09 (q, J = 7.1, 2H), 3.36 (brd, J = 14.2, 1H), 3.04 (dd, J = 16.4, 6.7, 1H), 1.29 (d, J = 6.8, 3H), 1.22 (t, J = 7.1, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 198.8, 155.9, 136.9, 133.3, 128.7, 128.1, 60.7, 44.20, 44.15, 20.4, 14.6; MS (EI, 70 ev) 236 (M+1 +, 10), 162 (56), 146 (60), 116 (40), 105 (100), 75 (35); Anal. Calcd. for C 13 H 17 N 3 : C, 66.36; H, 7.28; N, 5.95; Found: C, 66.64; H, 7.08; N, 5.59; TLC R f 0.30 (EtAc/hexanes, 1/4). 3-(1-Methyl-3-oxo-3-phenyl-propyl)-oxazolidin-2-one (1b ) 1 1 H NMR (400 MHz, CDCl 3 ) δ 7.96 (d, J = 7.5, 2H), 7.57 (t, J = 7.5, 1H), 7.47 (t, J N = 7.5, 2H), 4.34 (sext, J = 6.9, 1H), 4.29 (t, J = 8.0, 2H), (m, 2H), 3.47

5 S5 (dd, J = 16.2, 7.2, 1H), 3.14 (dd, J = 16.2, 6.6, 1H), 1.35 (d, J = 6.9, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 197.8, 157.5, 136.5, 133.4, 128.7, 128.2, 62.0, 46.8, 42.6, 42.5, 17.7; MS (EI, 20 ev) (C 13 H 15 N 3, 233.3) (M+1 +, 24), 189 (42), 146 (24), 128 (38), 114 (64), 105 (82), 84 (76), 70 (100), 54 (22); TLC R f 0.35 (EtAc/hexanes, 2/1). N-(1-Methyl-3-oxo-3-phenyl-propyl)-benzamide (1c ) 2 1 H NMR (400 MHz, CDCl 3 ) δ 7.98 (d, J = 7.3, 2H), 7.77 (d, J = 7.1, 2H), 7.58 HN (t, J = 7.3, 1H), (m, 5H), 7.03 (br d, J = 7.5, 1H), (m, 1H), 3.47 (dd, J = 16.8, 4.2, 1H), 3.20 (dd, J = 16.8, 6.0, 1H), 1.41 (d, J = 6.8, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 199.7, 166.7, 136.9, 134.6, 133.5, 131.4, 128.7, 128.5, 128.1, 126.9, 43.2, 42.9, 20.1; MS (EI, 20 ev) (C 17 H 17 N 2, 267.3) (M+1 +, 16), 162 (22), 148 (14), 105 (100), 77 (66), 54 (16); TLC R f 0.37 (EtAc/hexanes, 1/2). 4-Methyl-N-(1-methyl-3-oxo-3-phenyl-propyl)-benzenesulfonamide (1d ) 3 HN S 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (d, J = 7.5, 2H), 7.54 (d, J = 8.2, 2H), 7.55 (t, J = 7.5, 1H), 7.43 (t, J = 7.5, 2H), 7.23 (d, J = 8.2, 2H), 5.36 (d, J = 8.0, 1H), (m, 1H), 3.20 (dd, J = 17.2, 4.4, 1H), 3.05 (dd, J = 17.2, 6.5, 1H), 2.37 (s, 3H), 1.20 (d, J = 6.7, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 198.4, 143.3, 137.9, 136.5, 133.5, 129.7, 128.6, 127.9, 127.0, 46.8, 44.4, 21.4, 21.2; MS (EI, 20 ev) (C 17 H 19 N 3 S, 317.4) 318 (M+1 +, 8), 198 (22), 162 (44), 155 (12), 105 (100), 91 (36), 77 (22); TLC R f 0.38 (EtAc/hexanes, 1/2). 4-Methyl-N-[1-methyl-3-oxo-3-(2-oxo-oxazolidin-3-yl)-propyl]-benzenesulfonamide (2a ) N HN S 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (d, J = 8.2, 2H), 7.28 (d, J = 8.2, 2H), 5.16 (d, J = 8.8, 1H), 4.39 (t, J = 8.1, 2H), 3.94 (t, J = 8.1, 2H), (m, 1H), 3.09 (dd, J = 16.2, 6.9, 1H), 3.02 (dd, J = 16.2, 5.8, 1H), 2.41 (s, 3H), 1.12 (d, J = 6.7, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 170.8, 153.5, 143.3, 138.1, 129.6, 127.0,

6 S6 62.2, 46.8, 42.4, 41.9, 21.5, 21.4; MS (EI, 20 ev) 327 (M+1 +, 42), 311 (68), 224 (46), 198 (62), 171 (84), 155 (100), 91 (64), 84 (64), 65 (14); Anal. Calcd. for C 14 H 18 N 2 5 S: C, 51.52; H, 5.56; N, 8.58; Found: C, 51.48; H, 5.09; N, 8.57; TLC R f 0.38 (EtAc/hexanes, 3/2). (3-xo-cyclohexyl)-carbamic acid benzyl ester (3a ) 1 1 H NMR (400 MHz, CDCl 3 ) δ (m, 5H), (m, 2H), 4.80 (br s, N H 1H), (m, 1H), (m, 1H), (m, 3H), (m, 2H), (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.5, 155.2, 136.2, 128.6, 128.2, 128.1, 66.8, 50.2, 47.9, 40.8, 31.1, 21.9; MS (EI, 20 ev) (C 14 H 17 N 3, 247.3) 248 (M+1 +, 30), 108 (48), 91 (100), 66 (10); TLC R f 0.30 (EtAc/hexanes, 1/2). 3-(3-xo-cyclohexyl)-oxazolidin-2-one (3b ) 4 1 H NMR (400 MHz, CDCl 3 ) δ 4.34 (t, J = 8.0, 2H), (m, 1H), 3.56 (td, J = N 15.9, 8.0, 2H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 207.6, 157.3, 62.0, 52.2, 45.1, 41.0, 40.4, 28.6, 21.9; MS (EI, 20 ev) (C 9 H 13 N 3, 183.2) 184 (M+1 +, 14), 140 (36), 126 (76), 113 (44), 96 (100), 88 (40), 69 (18), 56 (36); TLC R f 0.31 (EtAc). N-(3-oxo-cyclohexyl)-benzamide (3c ) 2 1 H NMR (400 MHz, CDCl 3 ) δ 7.81 (d, J = 7.1, 1H, NH), 7.74 (d, J = 7.2, 1H), N H (m, 1H), (m, 2H), 6.10 (d, J = 4.4, 1H), (m, 1H), (m, 1H), (m, 3H), (m, 1H), (m, 1H), (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.7, 166.7, 134.3, 131.7, 128.6, 126.9, 49.0, 47.7, 41.0, 30.8, 22.2; MS (EI, 20 ev) (C 13 H 15 N 2, 217.3) 217 (M +, 28), 189 (18), 122 (34), 105 (100), 96 (16), 77 (54), 54 (12); TLC R f 0.32 (EtAc/hexanes, 1/1). 4-Methyl-N-(3-oxo-cyclohexyl)-benzenesulfonamide (3d ) 5

7 S7 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (d, J = 8.2 2H), 7.30 (d, J = 8.2 2H), 5.18 N H S (d, J = 7.2, 1H), (m, 1H), (m, 1H), 2.42 (s, 3H), (m, 1H), (m, 2H), (m, 2H), (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.0, 143.7, 137.6, 129.8, 126.9, 52.4, 48.4, 40.5, 31.9, 21.6, 21.5; MS (EI, 20 ev) (C 13 H 17 N 3 S, 267.3) 267 (M +, 8), 224 (26), 210 (22), 155 (40), 112 (100), 91 (58), 66 (16); TLC R f 0.18 (EtAc/hexanes, 1/2). N-(3-xo-cyclopentyl)-benzamide (4a ) 3 N H 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 1H), (m, 2H), 6.44 (br s, 1H), (m, 1H), 2.74 (dd, J = 18.4, 7.4, 1H), (m, 2H), (m, 2H), (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 215.9, 167.6, 134.1, 131.7, 128.6, 126.9, 48.3, 44.9, 37.2, 29.8; MS (EI, 20 ev) (C 12 H 13 N 2, 203.2) 203 (M +, 8), 122 (36), 105 (100), 77 (46); TLC R f 0.22 (EtAc/hexanes, 1/1). 4-Methyl-N-(3-oxo-cycloheptyl)-benzenesulfonamide (5a ) S N H 1 H NMR (400 MHz, CDCl 3 ) δ 7.75 (d, J = 8.2, 2H), 7.30 (d, J = 8.2, 2H), 5.04 (d, J = 7.3, 1H), (m, 1H), 2.63 (dd, J = 13.9, 3.1, 1H), (m, 3H), 2.44 (s, 3H), (m, 6H); 13 C NMR (100 MHz, CDCl 3 ) δ 210.9, 143.5, 137.5, 129.8, 127.0, 50.1, 49.2, 43.9, 37.5, 25.0, 23.4, 21.5; MS (EI, 70 ev) 281 (M +, 8), 240 (14), 239 (100), 224 (50), 155 (60), 126 (50), 109 (22), 90 (80), 63 (10); Anal. Calcd. for C 14 H 19 N 3 S: C, 59.76; H, 6.81; N, 4.98; Found: C, 59.52; H, 7.06; N, 4.89; TLC R f 0.21 (EtAc/hexanes, 1/2). 3-Diphenylphosphanyl-propionitrile (6a ) 6 1 H NMR (400 MHz, CDCl 3 ) δ (m, 10H), 2.39 (m, 2H), 2.37 (m, 2H); 13 C NC P NMR (100 MHz, CDCl 3 ) δ (d, J CP = 12.0), (d, J CP = 19.0), 129.3, (d, J CP = 7.0), (d, J CP = 14.0), 24.2 (d, J CP = 15.5), 14.1 (d, J CP = 23.6); 31 P NMR (162 MHz, CDCl 3 ) δ ; MS (EI, 20 ev) (C 15 H 14 NP, 239.3) 239 (M +, 100), 211 (28), 199

8 S8 (24), 183 (52), 154 (16), 121 (24), 107 (24); TLC R f 0.35 (EtAc/hexanes, 1/9). 3-(Diphenyl-phosphinoyl)-cyclohexanone (3e ) 6 1 H NMR (400 MHz, CDCl 3 ) δ (m, 4H), (m, 6H), (m, P 2H), (m, 4H), (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ (d, J CP = 14.0), 131.6, ((d, J CP = 44.0)), (d, J CP = 41.0), (d, J CP = 4.0), (d, J CP = 5.0), (d, J CP = 12.0), 40.7, 39.0 (d, J CP = 3.0), 37.3 (d, J CP = 71.1), 25.9 (d, J CP = 15.3), 23.1 (d, J CP = 2.7); 31 P NMR (162 MHz, CDCl 3 ) δ 32.1; MS (EI, 20 ev) (C 18 H 19 2 P, 298.3) 298 (M +, 18), 229 (18), 202 (100), 155 (20), 77 (16); TLC R f 0.32 (EtAc). Dibenzyl (3-xo-cyclohexyl)-phosphonate (3f ) 7 1 H NMR (400 MHz, CDCl 3 ) δ (m, 10H), (dd, J = 11.7, 10.6, P 2H), (dd, J = 11.7, 8.0, 2H), (m, 1H), (m, 2H), (m, 4H), (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ (d, J cp = 17.0), (d, J cp = 5.0), 128.6, 128.5, 128.0, 67.63, 67.5 (d, J CP = 7.0), 41.0, 40.4 (d, J CP = 6.0), 36.2 (d, J CP = 145.0), 25.9 (d, J CP = 19.1), 24.4 (d, J CP = 4.6); 31 P NMR (162 MHz, CDCl 3 ) δ 30.4; MS (EI, 20 ev) (C 20 H 23 4 P, 358.4) 359 (M+1 +, 16), 267 (28), 185 (28), 161 (42), 107 (18), 91 (100); TLC R f 0.29 (EtAc/hexanes, 1/1). Diethyl (4-xo-chroman-2-yl)-phosphonate (7a ) 7 P CH 2 CH 3 CH 2 CH 3 1 H NMR (400 MHz, CDCl 3 ) δ 7.84 (dd, J = 8.3, 0.9, 1H), 7.45 (td, J = 8.4, 1.4, 1H), 7.01 (t, J = 7.8, 2H), (m, 1H), (m, 4H), (m, 1H), (m, 1H), 1.34 (t, J = 7.0, 3H), 1.32 (t, J = 7.0, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ (d, J CP = 16.0), (d, J CP = 14.0), 136.1, 126.9, 122.0, 120.9, 117.8, 72.7 (d, J CP = 173.9), 63.4 (d, J CP = 6.0), 63.1 (d, J CP = 7.0), 37.4, 16.3 (d, J CP = 5.3); 31 P NMR (162 MHz, CDCl 3 ) δ 17.95; MS (EI, 20 ev) (C 13 H 17 5 P, 284.2) 284 (M +, 64), 147 (100), 91 (16); TLC R f 0.32 (EtAc/hexanes, 2/1).

9 S9 3-(1H-indol-3-yl)-1-phenyl-butan-1-one (1e ) 8 1 H NMR (400 MHz, CDCl 3 ) δ 7.96 (dd, J = 7.9, 0.8, 3H), 7.69 (d, J = 7.9, 1H), N H (m, 1H), 7.44 (t, J = 7.8, 2H), 7.36 (d, J = 8.1, 1H), 7.20 (td, J = 7.2, 1.0, 1H), 7.13 (td, J = 7.9, 0.9, 1H), 7.03 (d, J = 2.3, 1H), (m, 1H), 3.48 (dd, J = 16.3, 4.9, 1H), 3.25 (dd, J = 16.3, 8.9, 1H), 1.47 (d, J = 6.9, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 199.7, 137.3, 136.5, 132.9, 128.5, 128.1, 126.3, 122.0, 121.5, 120.2, 119.2, 119.2, 111.2, 46.5, 27.1, 20.9; MS (EI, 20 ev) (C 18 H 17 N, 263.3) 263 (M +, 38), 158 (24), 144 (100), 105 (16), 77 (14); TLC R f 0.22 (EtAc/hexanes, 1/7). 3-(3-Methyl-1H-indol-2-yl)-cyclohexanone (3g ) 8 N H 1 H NMR (400 MHz, CDCl 3 ) δ 7.99 (br s, 1H), 7.55 (d, J = 7.5, 1H), 7.33 (d, J = 7.6, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), 2.28 (s, 3H), (m, 2H), (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 210.5, 135.9, 135.1, 129.1, 121.4, 119.3, 118.3, 110.4, 106.5, 47.2, 41.2, 36.4, 31.0, 25.4, 8.4; MS (EI, 20 ev) (C 15 H 17 N, 227.3) 227 (M +, 100), 212 (36), 184 (38), 170 (16), 157 (64), 156 (52), 130 (16); TLC R f = 0.23 (EtAc/hexanes, 1/3). 3-(5-Methyl-furan-2-yl)-cyclopentanone (4b ) 9 1 H NMR (400 MHz, CDCl 3 ) δ 5.91 (d, J = 3.0, 1H), 5.86 (d, J = 3.0, 1H), (m, 1H), 2.56 (dd, J = 18.6, 7.8, 1H), (m, 3H), (m, 1H), 2.26 (s, 3H), (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 218.1, 154.7, 151.1, 105.8, 105.2, 43.6, 37.8, 35.5, 28.6, 13.5; MS (EI, 20 ev) (C 10 H 12 2, 164.2) 164 (M +, 64), 163 (24), 135 (16), 109 (22), 108 (100), 83 (18), 57 (22); TLC R f 0.47 (EtAc/hexanes, 1/5). 3-(5-Methyl-thiophen-2-yl)-cycloheptanone (5b ) 1 H NMR (400 MHz, CDCl 3 ) δ 6.57 (d, J = 3.6, 1H), 6.54 (dd, J = 3.2, 1.0, 1H), S 3.17 (tt, J = 10.9, 2.8, 1H), 2.89 (dd, J = 14.5, 11.1, 1H), 2.77 (ddd, J = 14.5, 2.9,

10 S10 1.7, 1H), (dd, J = 9.4, 4.8, 2H), 2.42 (d, J = 0.9, 3H), (m, 1H), (m, 2H), (m, 2H), (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 212.7, 147.7, 137.4, 124.5, 122.2, 51.6, 43.9, 39.7, 37.8, 28.6, 23.9, 15.2; MS (EI, 70 ev) 208 (M +, 100), 166 (10), 165 (10), 151 (48), 150 (56), 149 (22), 135 (36), 124 (60), 123 (44), 111 (40), 97 (16); Anal. Calcd. for C 12 H 16 S: C, 69.19; H, 7.74; Found: C, 69.27; H, 8.01; TLC R f 0.29 (EtAc/hexanes, 1/15). 3-(2,4,6-Trimethoxy-phenyl)-cyclohexanone (3h ) 10 1 H NMR (400 MHz, CDCl 3 ) δ 6.12 (s, 2H), 3.79 (s, 3H), 3.77 (s, 6H), Me (m, 1H), 3.09 (dd, J = 14.1, 12.5, 1H), (m, 2H), (m, 2H), Me Me (m, 1H), (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 212.6, 159.5, 158.9, 112.6, 90.9, 55.5, 55.2, 45.5, 41.4, 34.0, 29.0, 25.6; MS (EI, 20 ev) (C 15 H 20 4, 264.3) 264 (M +, 100), 263 (78), 233 (42), 221 (76), 207 (82), 194 (38), 181 (54), 178 (18), 151 (22), 121 (20); TLC R f 0.23 (EtAc/hexanes, 1/5). References: (1) Kobayashi, S.; Kakumoto, K.; Sugiura, M. rg. Lett. 2002, 4, (2) Takasu, K.; Nishida, N.; Ihara, M. Synlett. 2004, (3) Lee, A. S.-Y.; Wang, S.-H.; Chang, Y.-T.; Chu, S.-F. Synlett. 2003, (4) Xu, L.-W.; Xia, C.-G.; Hu, X.-X. Chem. Commun. 2003, (5) Molander, G. A.; Stengel, P. J. J. rg. Chem. 1995, 60, (6) Hayashi, M.; Matsuura, Y.; Watanabe, Y. Tetrahedron Lett. 2004, 45, (7) Mori, I.; Kimura, Y.; Nakano, T.; Matsunaga, S.-I.; Iwasaki, G.; gawa, K. H. Tetrahedron Lett. 1997, 38, (8) Srivastava, N.; Banik, B. K. J. rg. Chem. 2003, 68, (9) Dyker, G.; Muth, E.; Hashmi, A.; Stephen K.; Ding, L. Adv. Synth. Catal. 2003, 345, (10) Shi, Z.; He, C. J. rg. Chem. 2004, 69, 3669.

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