Guanidine and guanidinium salt catalyzed enantioselective phosphorus carbon bond formation reactions 4

Chapter Chapter Experimental 81 Chapter 4.1 General Procedures H and 13 C NMR spectra were recorded on a Bruker ACF300 (300MHz) or AMX500 (500MHz) spectrometer. Chemical shifts are reported in parts per million (ppm). The residual solvent peak was used as an internal reference. Low resolution mass spectra were obtained on a VG Micromass 7035 spectrometer in EI mode, a Finnigan/MAT LCQ spectrometer in ESI mode, and a Finnigan/MAT 95XL-T mass spectrometer in FAB mode. All high resolution mass spectra were obtained on a Finnigan/MAT 95XL-T spectrometer. Infrared spectra were recorded on a BIO-RAD FTS 165 FTIR spectrometer. Enantiomeric excesses were determined by chiral HPLC analysis on Jasco HPLC units, including a Jasco DG-980-50 Degasser, a LG-980-02 Ternary Gradient Unit, a PU-980 Intelligient HPLC Pump, UV-975 Intelligient UV/VIS Detectors, and an AS-950 Intelligient Sampler. Optical rotations were recorded on a Jasco DIP-1000 polarimeter. Melting points were determined on a BÜCHI B-540 melting point apparatus. Analytical thin layer chromatography (TLC) was performed with Merck pre-coated TLC plates, silica gel 60F-254, layer thickness 0.25 mm. Flash chromatography separations were performed on Merck 60 (0.040 0.063mm) mesh silica gel. THF was freshly distilled from sodium/benzophenone before use. CH2Cl2 were distilled from calcium hydride and stored under N2 atmosphere. All distilled solvents were stored under N2. All other reagents and solvents are commercial grade and were used as supplied without further purification, unless otherwise stated. 4.2 Preparation and characterization of P-nucleophiles 4.2.1 Preparation of phosphine oxides Phosphine oxide 125a was purchased form Sigma-Aldrich and used without 82 Chapter purification. 125b-f were prepared using the literature protocol.1 Data for 125b was consistent with data reported in the literature. 4.2.2 Characterization of phosphine oxides (125c) di-4-phenylphenyl phosphine oxide White solid. mp 159.7-161.0 oC. 1H NMR (300 MHz, H P O Ph Ph CDCl3, ppm): δ 7.39-7.85 (m, 18H), 8.29 (d, J = 418.9 Hz, 1H). 13C NMR (75 MHz, CDCl3, ppm): δ 127.0 (s), 127.3 (d, J = 13.1 Hz), 128.0 (s), 128.9 (d, J = 23.4 Hz), 130.4 (s), 131.0 (d, J = 12.0 Hz), 139.4, 145.1 (d J = 2.7 Hz). 31 P NMR (121MHz, CDCl3, ppm, proton-coupled): δ 21.5 (J = 418.9 Hz). IR (KBr) 760, 1128, 3025 cm-1. LRMS ESI m/z 354.9 (M+), HRMS ESI m/z 355.1246 (M+H+), calc. for C24H20OP 355.1252. (125d) di-2-ethylphenyl phosphine oxide White solid. mp 67.6-68.1 oC. 1H NMR (300 MHz, CDCl3, ppm): δ 1.04 (t, J = 7.5 Hz, 6H), 2.72 (q, J = 7.5, 15.0 Hz, 4H), 7.27- H P O 7.73 (m, 8H), 8.27 (d, J = 474.8 Hz, 1H). 13 C NMR (75 MHz, CDCl3, ppm): δ 14.9 (s), 26.4 (d, J = 6.6 Hz), 125.9 (d, J = 12.7 Hz), 129.2 (d, J = 10.5 Hz), 129.9 (s), 132.3 (d, J = 12.2 Hz), 132.6 (d, J = 2.2 Hz), 147.2 (d, J = 9.97). 31 P NMR (121MHz, CDCl3, ppm, proton-coupled): δ 17.7 (J = 474.8 Hz). IR (KBr) 754, 1180, 3054 cm-1. LRMS ESI m/z 259.2 (M+H+), HRMS ESI m/z 259.1247 (M+H+), calc. for C16H20OP 259.1252. (125e) di-2-naphthyl phosphine oxide White solid. mp 90.4-92.0 oC. 1H NMR (300 MHz, H P O 83 Chapter CDCl3, ppm): δ 7.51-8.40 (m, 14H), 8.33 (d, 1H, J = 480.9 Hz). 13C NMR (75 MHz, CDCl3, ppm): δ 125.0 (d, J = 12.2 Hz), 127.0 (s), 127.8 (d, J = 12.2 Hz), 128.3 (s), 128.7 (s), 128.9 (s) , 129.0 (s), 132.4 (d, J = 13.8), 132.7 (d, J = 11.1 Hz), 134.9 (d, J = 2.2 Hz). 31P NMR (121MHz, CDCl3, ppm, proton-coupled): δ 22.3 (J = 480.8 Hz). IR (KBr) 748, 1188, 3050 cm-1. LRMS EI m/z 301.9 (M-H+), HRMS EI m/z 302.0847 (M+), calc. for C20H15OP 302.0861. (125f) di-1-naphthyl phosphine oxide White solid. mp 164.9-165.6 oC. 1H NMR (300 MHz, CDCl3, H P O ppm): δ 7.43-8.41 (m, 14H), 8.89 (d, 1H, J = 481.4 Hz). 13 C NMR (75 MHz, CDCl3, ppm): δ 124.8 (s), 125.1 (d, J = 8.9 Hz), 126.6 (d, J = 13.8 Hz), 127.7 (s), 127.9 (s), 129.1 (s), 132.7 (d, J = 24.9 Hz), 133.0 (s), 133.5 (d, J = 8.9 Hz), 133.6 (d, J = 2.8 Hz). 31P NMR (121MHz, CDCl3, ppm, protoncoupled): δ 19.2 (J = 481.4 Hz). (KBr) 773, 1179, 3045 cm-1. LRMS EI m/z 302.0 (M+), HRMS EI m/z 302.0850 (M+), calc. for C20H15OP 302.0861. 4.2.3 Preparation of H-phosphinates Benzylphosphinic acids were prepared using the modified protocol2: Ammonium phosphinate (2eq.) and hexamethyldisilazane (2.2 eq.) were heated together at 100100 oC under nitrogen for 1-2 h in a 100ml 3-neck flask fitted with a condenser. The system was cooled to oC and dry DCM was injected, followed by benzyl bromide (1eq.). The reaction was stirred overnight at room temperature, filtered and the solvent removed. Basified with sat. K2CO3, the aqueous layer was washed with Et2O x 2. Acidify with HCl solution, followed by extraction with DCM. Remove of solvent, no further purification was required. 84 Chapter H-phosphinates 179 were prepared using the literature protocol.3 4.2.4 Characterization of H-phosphinates (179a) benzyl benzylphosphinate colorless oil. 1H NMR (500MHz, CDCl3, ppm): δ 3.19 (dd, O P H O 2H, J = 2.8, 18.6 Hz), 4.97 (dd, 1H, J = 8.9, 12.0 Hz), 5.08 (dd, 1H, J = 10.1, 12.0 Hz), 7.06 (dt, 1H, J = 1.9, 3.8, 547.9 Hz), 7.18-7.35 (m, 10H). 13 C NMR (125MHz, CDCl3, ppm): δ 36.9 (d, J = 87.5 Hz), 67.5 (d, J = 6.4 Hz), 127.1 (d, J = 3.6 Hz), 127.8 (s), 128.4 (s), 128.5 (s), 128.7 (d, J = 2.7 Hz), 129.4 (d, J = 7.3 Hz), 129.6 (d, J = 6.4 Hz), 135.4 (d, J = 5.5 Hz). 31P NMR (202MHz, CDCl3, ppm, proton-coupled): δ 37.1 (J = 547.93 Hz). IR (KBr) 738.63, 1176.87, 61.32, 1602.46, 3060.32 cm-1. LRMS (ESI) m/z 269.0 (M+Na+), HRMS ESI m/z cation 269.0712 (M+Na+), calc. for C14H15O2PNa 269.0702. (179b) benzyl naphthalen-2-ylmethylphosphinate O P H O White solid. mp 93.3 – 94.6 oC. 1H NMR (500MHz, CDCl3, ppm): δ 3.38 (d, 2H, J = 18.30 Hz), 5.01 (dd, 1H, J = 8.7, 11.9 Hz), 5.13 (dd, 1H, J = 10.3, 11.9 Hz), 7.15 (dt, 1H, J = 1.9, 3.8, 548.6 Hz), 7.27-7.83 (m, 12H). 13C NMR (125MHz, CDCl3, ppm): δ 37.4 (d, J = 86.5 Hz), 67.9 (d, J = 7.3 Hz), 126.1 (s), 126.4 (s), 127.1 (d, J = 7.3 Hz), 127.7 (d, J = 5.5 Hz), 128.0 (s), 128.6 (d, J = 4.6 Hz), 128.7 (d, J = 2.7 Hz), 132.5 (d, J = 2.7 Hz), 133.5 (d, J = 3.6 Hz), 135.6 (d, J = 6.4 Hz). 31P NMR (202MHz, CDCl3, ppm, proton-coupled): δ 37.0 (J = 548.6 Hz) IR (KBr) 732.46, 1216.50, 1598.18, 3055.77 cm-1. LRMS EI m/z 319.1 (M+Na+), HRMS EI m/z 319.0871 (M+Na+), calc. for C18H17O2PNa 319.0858. 85 Chapter (179c) benzyl 4-(trifluoromethyl)benzylphosphinate White solid. mp 85.6 – 87.5 oC. 1H NMR (500MHz, F3C O P H O CDCl3, ppm): δ 3.25 (d, 2H, J = 18.3 Hz), 5.00 (dd, 1H, J = 8.8, 12.0 Hz), 5.11 (t, 1H, J = 11.4 Hz), 7.11 ( d, 1H, J = 557.7 Hz), 7.26-7.56 (m, 9H). 13C NMR (125MHz, CDCl3, ppm): δ 37.7 (d, J = 86.5 Hz), 68.8 (d, J = 7.3Hz), 123.6 (s), 125.8 (s), 126.4 (d, J = 3.6 Hz), 126.5 (t, J = 3.7 Hz), 128.8 (s), 129.4 (d, J = 9.1 Hz), 130.2 (d, J = 3.7 Hz), 130.5, 130.9 (d, J = 6.4 Hz) , 134.5 (d, J = 6.4 Hz), 135.9 (d, J = 5.5 Hz). 31P NMR (202MHz, CDCl3, ppm, proton-coupled): δ 34.6 (J = 557.5 Hz). 19 F NMR (282MHz, CDCl3, ppm): δ 13.3. IR (KBr) 744, 1121, 1164, 1629 cm-1. LRMS (ESI) m/z 337.0 (M+Na+). The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 90/10; flow rate 0.5 ml/min; temp 25 °C; detection UV 210 nm; retention time: 25.5, 28.2min. (179e) benzyl 4-methylbenzylphosphinate White solid. mp 55.1 – 57.2 oC. 1H NMR (500MHz, O P H O CDCl3, ppm): δ 2.33 (d, 3H, J = 2.4 Hz), 3.18 (dd, 2H, J = 2.9, 18.3 Hz), 5.00 (dd, 1H, J = 8.6, 11.9 Hz), 5.11 (dd, 1H, J = 10.1, 11.8 Hz), 7.07 (dt, 1H, J = 1.9, 3.8, 546.7 Hz), 7.09 – 7.37 (m, 9H). 13C NMR (125MHz, CDCl3, ppm): δ 21.7 (s), 37.4 (d, J = 87.5 Hz), 68.4 (d, J = 7.3 Hz), 127.0 (d, J = 7.3 Hz), 128.6 (s), 129.2 (s), 129.3 (s), 130.3 (d, J = 2.7 Hz), 130.4 (s), 136.3 (d, J = 5.5 Hz), 137.7 (d, J = 4.6 Hz). 31P NMR (202MHz, CDCl3, ppm, protoncoupled): δ 37.7 (J = 546.7 Hz). IR IR (KBr) 732.62, 1218.83, 1612.54, 3033.64 cm-1. LRMS EI m/z 283.0, (M+Na+), HRMS EI m/z 283.0865 (M+Na+), calc. for 86 Chapter C15H17O2PNa 283.0858. (179f) benzyl cinnamylphosphinate White solid. mp 39.8 – 42.8 oC. 1H NMR (500MHz, O P H O CDCl3, ppm): δ 2.81 (m, 2H), 5.07 (dd, 1H, J = 8.8, 12.0 Hz), 5.17 (m, 1H), 6.52 (m, 1H), 7.09 (dt, 1H, J = 1.9, 3.8, 548.0 Hz), 7.23 – 7.41 (m, 10H). 13C NMR (125MHz, CDCl3, ppm): δ 34.4, 35.1, 68.4, 68.5, 117.0 (two peaks), 117.4, 117.5, 126.9 (two peaks), 127.6, 128.4, 128.5, 128.8, 129.1, 129.2, 129.3, 129.4, 136.2, 136.8, 136.9, 137.0 (two peaks). 31 P NMR (202MHz, CDCl3, ppm, proton-couple): δ 36.7 (J = 548.0 Hz). IR (KBr) 730.02, 1222.14, 1643.65, 3030.67 cm-1. LRMS EI m/z 295.1 (M+Na+), HRMS EI m/z 295.0872 (M+Na+), calc. for C16H17O2PNa 295.0858. 4.3 Preparation and characterization of bicyclic guanidine and guanidinium salts catalysts. 4.3.1 Preparation of bicyclic guanidine Bicyclic guanidine 114b was prepared using the protocol reported.4 4.3.2 Preparation and characterization of guanidinium salts catalysts. To a 50 ml RBF containing (1S,2S)-1,2-diphenylethane-1,2-diamine 166 (1.06 g, mmol, 1eq.) and pyrrolidinium salt 167 (3.43 g, 12.5 mmol, 2.5eq.) was added 20ml DCM, then 4.2 ml Et3N (6eq.) was added. Stirred at room temperature for 36h, and monitored by TLC (MeOH/DCM mixture 1/4). Remove of the solvent, basified the residue with saturated K2CO3 solution. Wash the solution with diethyl ether (x 6). Acidify the aqueous layer with HBF4 solution (Caution: CO2 generated!) until PH = 1. The crude product was collected via reduce pressure filtration and purified by 87 Chapter recrystallization from hot MeOH and n-hexane. (168.2HBF4) (1S,2S)-N1,N2-bis(dipyrrolidin-1-ylmethylene)Ph Ph N N N N H H BF N 1,2-diphenylethane-1,2-diaminium tetrafluoroborate N White solid. mp 262.8 – 265.3 oC. 70% yield. [α]26 D -27.5 (c BF .2HBF4 0.73, CHCl3). 1H NMR (500MHz, CDCl3, ppm): δ 1.85-1.92 (br, 16H), 3.02 (br, 8H), 3.35-3.36 (br, 8H), 5.49 (d, 2H, J = 6.31Hz), 6,69 (br, 2H), 7.21-7.45 (m, 10H) 13 C NMR (125MHz, CDCl3, ppm): δ 25.3, 50.1, 63.8, 127.0, 128.2, 128.8, 137.1, 156.0 19 F NMR (202MHz, CDCl3, ppm): δ -74.3. IR (KBr) 763.92, 1083.36, 1600.51, 2975.13 cm-1. LRMS (ESI) m/z 513.3 (M+H+), HRMS (ESI) m/z cation 513.3694 (M+H+), calc. for C32H45N6 513.3700 To a vial containing 100 mg catalyst 168.2HBF4 was added saturated NaOH solution, stirred at room temperature for 5h. Extracted with DCM, and dried with K2CO3. Catalyst 168 (base) was obtained (checked by 19 F NMR, no 19 F peak was observed). Catalyst 168.HBF4 and 168 with other numbers of protons were prepared by mix catalyst 168.2HBF4 and 168 (base). Stirred with NaBArF4 (1 eq.) in DCM for 1h, filter through celite. (168.BArF4) (1S,2S)-N-(dipyrrolidin-1-ylmethylene)-2-(dipyrrolidin-1-ylmethylene- amino)-1,2-diphenylethanaminium tetrakis(3,5-bis(trifluoromethyl) phenyl)borate F3 C Ph Ph N N F3 C N N H N BArF 168 .HBAr F pale CF3 CF3 F yellow foam. mp 160.5 – 163.3 oC. [α] 25 D B BAr = N F3 C CF3 F3 C CF3 +18.8 (c 0.26, CHCl3). 1H NMR (500MHz, CDCl3, ppm): δ 1.70 (br, 16H), 3.05 (br, 16H), 4.58 (s, 2H), 7.15-7.71 (m, 12H). 13 C NMR 88 Chapter (125MHz, CDCl3, ppm): δ 25.9, 49.6, 67.5, 118.1, 122.0, 124.1, 126.3, 126.9, 128.5, 128.6, 129.1, 129.5, 129.7, 129.9, 135.5, 141.7, 156.5, 161.8, 162.2, 162.6, 163.0. 19F NMR (202MHz, CDCl3, ppm): δ 13.5.IR (KBr) 713.30, 1125.35, 1596.89, 2979.02 cm-1. LRMS FAB m/z cation 862.9 (M-H+) HRMS (FAB) m/z cation 863.0685 (M), calc. for C32H12BF24 863.0654. 4.4 Protocol for bicyclic guanidine-catalyzed phospha-Michael reactions and characterization of phospha-Michael reaction products 4.4.1 Protocol for bicyclic guanidine-catalyzed phospha-Michael reactions To a 50 ml RBF containing catalyst 114b (1.8 mg, 0.008 mmol, 10 mol%) and a stirring bar, di(1-naphthyl) phosphine oxide 125f (24.2 mg, 0.08 mmol) and anhydrous diethyl ether (25 ml), were added in this sequence and stirred at –40 oC for 1h. 4-Chloro-β-nitrostyrene (73.4 mg, 0.4 mmol, eq.) was added to the reaction mixture and stirred at –40 oC for 12 h. Solvent was removed from the reaction mixture and loaded onto a short silica gel column. This was followed by flash chromatography (gradient elution with n-hexane–ethyl acetate mixtures; 10 : to : 1). Adduct 127a (36.5 mg) was obtained as a white solid in 94% yield and 96% ee. 4.4.2 Characterization of phospha-Michael reaction products (126a) (2-nitro-1-phenylethyl)diphenyl phosphine oxide White solid. mp 204.3-205.1 oC. 64% yield, 60% ee; after 27 recrystallization from MeOH, 96% ee. [α] D O P -58.7 (c 0.45, CHCl3). 1H NMR (300 MHz, CDCl3, ppm): δ 4.37-4.45 (m, 1H), NO 4.72-4.78 (m, 1H), 5.05-5.15 (m, 1H), 7.19-8.01(m, 15H). 13 C NMR (75 MHz, CDCl3, ppm): δ 45.3 (d, J = 63.7 Hz), 75.7 (d, J = 6.1 Hz), 128.4 (d, J = 12.2 Hz), 128.8 (s), 129.3 (d, J = 11.6 Hz), 129.4 (d, J = 5.0 Hz), 130.7 (s), 130.9 89 Chapter (s), 131.0 (d, J = 4.4 Hz), 131.2 (s), 131.6 (d, J = 5.5 Hz), 132.0(d, J = 2.8 Hz), 132.7 (d, J = 2.8 Hz). 31P NMR (121MHz, CDCl3, ppm): δ 30.5. IR (KBr) 708, 1185, 1551, 3060 cm-1. LRMS (ESI) m/z 374.0 (M+Na+), HRMS (ESI) m/z 374.0932 (M+Na+), calc. for C20H18NO3PNa 374.0917. The ee was determined by chiral HPLC; CHIRALCEL IA (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 9.1 and 14.4 min. purif ied by recrystalization af ter flash chromatography (126b) (2-nitro-1-phenylethyl)di-4-fluorophenyl phosphine oxide White solid. mp 186.4-187.7 oC. 92% yield, 60% ee; after F recrystallization from tBuOMe/CH2Cl2 mixture, >99% ee. O P F 27 [α] D -142.4 (c 0.71, CHCl3). 1H NMR (300 MHz, CDCl3, ppm): δ 4.31-4.40 (m, 1H), 4.71-4.79 (m, 1H), 5.03-5.13 (m, NO 1H), 6.94-8.02 (m, 13H). 13C NMR (75 MHz, CDCl3, ppm): δ 46.0 (d, J = 65.3 Hz), 75.6 (d, J = 5.5 Hz), 115.7 (d, J = 13.3 Hz), 116.0 (13.3 Hz), 116.8 (d, J = 12.7 Hz), 117.1 (d, J = 12.7 Hz), 128.5 (s), 128.9 (s), 129.4 (d, J = 7.7 90 Chapter [α]28 D -142.9 (c 1.38, CHCl3). H NMR (500MHz, CDCl3, ppm): δ 1.94 (s, 3H), 5.37 (m, 1H), 5.42 (dd, 1H, J = 4.41, 8.20Hz), 5.70 (dd, 1H, J = 4.41, 15.13Hz) 6.08-8.82 (m, 23H). 13C NMR (125MHz, CD2Cl2, ppm): δ 21.3, 56.6 (d, J = 78.4 Hz), 121.3, 121.3, 124.7, 124.9, 125.0, 125.1, 126.3, 126.4, 126.4, 126.4, 126.5, 126.6, 126.6, 126.7, 126.9, 126.9, 127.2, 127.5, 127.6, 127.7, 127.8, 127.8, 127.9, 128.2, 128.3, 129.2, 129.3, 129.4, 129.6, 129.9, 132.6, 132.7, 133.1, 133.2, 133.7, 133.7, 133.8 133.8, 133.8, 133.9, 133.9, 134.1, 134.1, 134.4, 134.4, 135.1, 135.1, 136.0, 136.1, 138.6, 143.7. 31 P NMR (252MHz, CDCl3, ppm): δ 35.9. IR (KBr) 741.10, 1159.06, 1595.44, 3029.65 cm-1. LRMS (ESI) m/z 610.0 (M+Na+), HRMS (ESI) m/z 610.1602 (M+Na+), calc. for C38H30O3NPSNa 610.1576. The ee was determined by chiral HPLC; CHIRALCEL IC (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 23.7 and 37.0 min. (169i) N-((1S)-(cyclohexa-1,3-dienyl(phenyl)phosphoryl)(phenyl)methyl)-biphenyl-4- 115 Chapter sulfonamide -50 oC. White solid. mp 185.1 – 188.6 oC. 75% yield, 56% ee. 1H Ph NMR (500MHz, CDCl3, ppm): δ 5.43 (t, 1H, J = 9.8Hz), 6.75-8.70 (m, 25H). NHSO O P 13 C NMR (125MHz, CDCl3, ppm): δ 58.3 (d, J = 74.7 Hz), 127.4, 127.8, 128.0, 128.2, 128.3, 128.8, 128.8, 128.9, 129.5, Ph 129.6, 129.6, 129.9, 129.9, 130.5, 130.6, 131.3, 132.0, 132.0, 132.5, 132.6, 132.9, 132.9, 133.1, 140.5, 140.6, 145.1. 31P NMR (252MHz, CDCl3, ppm): δ 32.8. IR (KBr) 734.4, 1161.2, 1589.2, 3056.2 cm-1. LRMS (ESI) m/z 546.0 (M+Na+), HRMS (ESI) m/z 590546.1245 (M+Na+), calc. for C31H26NO3PSNa 546.1263. The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 50/50; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 23.4, 32.6min. (169j) (S)-N-((bis(2-(trifluoromethyl)phenyl)phosphoryl)(phenyl)methyl)biphenyl-4sulfonamide -60 oC. White solid. mp 206.3 – 208.8 oC. 93% yield, 82% ee. Ph H NMR (500MHz, CDCl3, ppm): δ 5.83 (t, 1H, J = 10.72Hz), 6.51-8.85 (m, 22H). F3 C NHSO O P F3 C 13 C NMR (125MHz, CDCl3, ppm): δ 57.7 (d, J = 131.8 Hz), 118.5, 118.7, 122.1, 122.3, 125.8, 126.0, Ph 126.7, 126.7, 127.5, 127.8, 128.0, 128.4, 129.5, 130.0, 130.2, 130.5, 130.6, 130.9, 131.7, 131.9, 132.2, 132.3, 132.4, 132.7, 133.2, 133.6, 134.0, 134.5, 135.4, 135.5, 137.3, 139.6, 140.4, 145.5. 31P NMR (252MHz, CDCl3, ppm): δ 32.3. 19F NMR (282MHz, CDCl3, ppm): δ 19.4, 19.8. IR (KBr) 768.9, 1167.6, 1637.5 cm-1. LRMS (ESI) m/z 682.0. (M+Na+), HRMS (ESI) m/z 682.1024. (M+Na+), calc. 116 Chapter for C33H24F6NO3PSNa 682.1011. The ee was determined by chiral HPLC; CHIRALCEL IC (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 0.3 ml/min; temp 25 °C; detection UV 210 nm; retention time: 6.4, 10.4min. (169k) N-((1S)-(naphthalen-1-yl(phenyl)phosphoryl)(phenyl)methyl)benzenesulfonamide -60 oC. White solid. mp 185.1 – 188.6 oC. 90% yield, 75, NHSO2Ph 85% ee. 1H NMR (500MHz, CDCl3, ppm): δ 5.60 (t, 1H, J = Ph 10.09Hz) or 5.66 (t, 1H, J = 10.09Hz), 6.41-9.15 (m, 22H). O P 13 C NMR (125MHz, CDCl3, ppm): δ 58.4 (dd, J = 69.2, 75.6 Hz), 124.9, 125.0, 125.5, 125.6, 125.7, 126.0, 126.5, 126.6, 126.8, 126.8, 126.9, 127.0, 127.6, 127.6, 127.7, 127.7, 127.8, 127.9, 128.0, 128.1, 128.6, 128.6, 128.7, 129.2, 129.3, 129.3, 129.4, 129.5, 129.6, 129.8, 129.8, 131.2, 131.6, 131.6, 131.7, 132.0, 132.2, 132.4, 132.4, 132.7, 132.8, 132.9, 133.0, 133.3, 133.3, 133.7, 133.7, 133.9, 134.0, 134.2, 134.3, 134.4, 134.4, 134.5, 134.6, 134.7, 141.7, 141.9, 143.0. 31P NMR (252MHz, CDCl3, ppm): δ 34.2, 35.4. IR (KBr) 734.4, 1161.2, 1589.2, 3056.2 cm-1. LRMS (ESI) m/z 682.0. (M+Na+), HRMS (ESI) m/z 520.0 (M+Na+), calc. for C29H24NO3PSNa 520.1107. The ee was determined by chiral HPLC; CHIRALCEL IC (4.6 mm i.d. x 250 mm); hexane/2-propanol 50/50; flow rate 0.3 ml/min; temp 25 °C; detection UV 210 nm; retention time: 31.8, 65.9min; 48.2, 86.1min (180a) (S)-benzyl benzyl((R)-(4-methylphenylsulfonamido)(phenyl)methyl)phosphinate White solid. mp 242.4 – 243.3 oC. 83% yield, 94% ee of syn, Ph O P O Ph NHTs 117 Chapter 55% ee of anti. dr = 6:1. [α]26 D -23.1 (c 0.32, CHCl3). H NMR (500MHz, CDCl3, ppm): δ 2.26 (s, 3H), 2.99 (d, 2H, J = 15.13Hz), 4.77 (dd, 1H, J = 7.57, 15.76Hz), 4.87 (d, 2H, J = 7.56Hz), 6,07 (br, 1H), 6.93-7.41 (m, 19H) 13 C NMR (125MHz, CDCl3, ppm): δ 22.0, 35.2 (d, J = 88.4 Hz), 57.4, 58.1, 68.8, 68.9, 127.7, 127.7, , 127.8, 128.8, 128.8, 128.9, 129.1, 129.2, 129.2, 129.3, 129.8, 130.4, 130.5, 130.9, 130.9, 133.6, 136.8, 136.8, 138.1, 143.8 31P NMR (500MHz, CDCl3, ppm): δ 45.5. IR (KBr) 735.17, 1157.66, 1600.58, 3115.53 cm-1. LRMS (ESI) m/z 528.1 (M+Na+), HRMS (ESI) m/z 528.1366 (M+Na+), calc. for C28H28NO4PSNa 528.1369. The ee was determined by chiral HPLC; CHIRALCEL IA (4.6 mm i.d. x 250 mm); hexane/2-propanol 90/10; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 41.5, 55.9min; 55.9min; 47.2, 63.0min. (180b) (S)-benzyl benzyl((R)-(4-fluorophenyl)(phenylsulfonamido)methyl)phosphinate White solid. mp 154.3 – 158.0 oC. 90% yield, 90% ee of syn, 30% ee of anti. dr = 6:1. [α]29 D -18.9 (c 1.50, CHCl3). H NMR (500MHz, CDCl3, ppm): δ 3.00 (d, 2H, J = 118 Chapter 15.76Hz), 4.80(dd, 1H, J = 10.08, 15.76Hz), 4.98 (dd, 2H, J = 1.89, 6.93Hz), 6.66 (br, 1H), 6.70-7.54 (m, 19H). 13C O H N S O O P O NMR (125MHz, CDCl3, ppm): δ 35.2 (d, J = 89.3 Hz), 57.1 (d, J = 93.8 Hz), 69.2 (d, J = 7.3 Hz), 116.1, 116.2, 127.1, 127.6, 127.8, 127.9, 128.7, 129.0, 129.2, 129.2, F 129.3, 129.4, 129.8, 130.3, 130.4, 130.6, 130.7, 130.7, 130.8, 133.0, 133.4, 136.7, 136.7, 141.3, 162.2, 162.2, 164.2, 164.2. (two peaks). 31 P NMR (252MHz, CDCl3, ppm): δ 44.9 19 F NMR (282MHz, CDCl3, ppm): δ -37.2. IR (KBr) 735.08, 1164.72, 1604.77, 3113.69 cm-1. LRMS (ESI) m/z 532.1 (M+Na+), HRMS (ESI) m/z 532.1133 (M+Na+), calc. for C27H25FNO4PSNa 532.1118. The ee was determined by chiral HPLC; CHIRALCEL IA+ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 27.2, 33.9min; 32.1, 36.0min. (180c) (S)-benzyl benzyl((R)-(4-chlorophenyl)(phenylsulfonamido)methyl)phosphinate 119 Chapter White solid. mp 160.1 – 163.3 oC. 90% yield, 92% ee of syn, 15% ee of anti. [α] 30 D -10.7 (c 1.66, CHCl3). H O H N S O O P O NMR (500MHz, CDCl3, ppm): δ 3.02 (dd, 2H, J = 3.16, 15.14Hz), 4.82(dd, 1H, J = 9.46, 15.13Hz), 5.02 (dd, 2H, Cl J = 4.73, 6.62Hz), 6.85 (br, 1H), 7.00-7.56 (m, 19H). 13C NMR (125MHz, CDCl3, ppm): δ 35.2 (d, J = 88.4 Hz), 57.4 (d, J = 92.9 Hz), 69.3 (d, J = 7.3 Hz), 127.1, 127.7, 127.8, 127.9, 129.0, 129.2, 129.2, 129.3, 129.8, 130.2, 130.2, 130.3, 130.7, 130.8, 132.2, 133.0, 133.4, 135.0, 135.0, 136.6, 136.7, 141.2. 31P NMR (252MHz, CDCl3, ppm): δ 44.7. IR (KBr) 734.92, 1163.47, 1593.62, 3106.12 cm-1. LRMS (ESI) m/z 548.1 (M+Na+), HRMS (ESI) m/z 548.0834 (M+Na+), calc. for C27H2535ClNO4PSNa 548.0823. The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 15.5, 25.7min; 18.4, 22.5min. (180d) 120 Chapter (S)-benzyl benzyl((R)-phenylsulfonamido(p-tolyl)methyl)phosphinate White solid. mp 153.2 – 156.6 oC 85% yield, 90% ee of O H N S O syn, 16% ee of anti. dr = 4:1. [α]26 D -21.8 (c 1.81, CHCl3). O P O H NMR (500MHz, CDCl3, ppm): δ 2.23 (s, 3H), 2.97 (d, 2H, J = 15.06Hz), 4.79(dd, 1H, J = 9.47, 15.34Hz), 4.96 (dd, 2H, J = 6.97Hz), 6.70 (br, 1H), 6.85-7.55 (m, 19H). 13 C NMR (125MHz, CDCl3, ppm): δ 21.7, 35.2 (d, J = 88.4 Hz), 57.8 (d, J = 93.8 Hz), 68.9 (d, J = 7.3 Hz), 127.6, 127.7, 127.7, 127.8, 128.6, 128.8, 128.9, 128.9, 129.1, 129.1, 129.1, 129.2, 129.9, 129.9, 130.6, 130.6, 130.8, 130.9, 132.7, 136.9, 137.0, 138.7, 138.7, 141.4. 31 P NMR (252MHz, CDCl3, ppm): δ 45.3. IR (KBr) 757.07, 1162.54, 1584.91 3067.42 cm-1. LRMS (ESI) m/z 528.1 (M+Na+), HRMS (ESI) m/z 528.1372 (M+Na+), calc. for C28H28NO4PSNa 528.1369. The ee was determined by chiral HPLC; CHIRALCEL IA (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 0.5 ml/min; temp 25 °C; detection UV 210 nm; retention time: 27.0, 40.0min; 29.9, 36.0min. 121 Chapter (180e) (S)-benzyl benzyl((R)-(4-methylphenylsulfonamido)(naphthalen-2-yl)methyl) phosphinate White solid. mp 153.6 – 155.5 oC 93% yield, 91% ee of syn, 40% ee of anti. dr = 6:1. [α]28 D -17.7 (c 0.47, O H N S O O P O CHCl3). 1H NMR (500MHz, CD2Cl2, ppm): δ 1.93 (s, 3H), 3.05 (p, 2H, J = 14.84, 14.84, 14.72, 14.72Hz), 4.92(dd, 1H, J = 8.98, 14.81Hz), 4.98 (m, 2H), 7.09- 7.52 (m, 21H). 13C NMR (125MHz, CD2Cl2, ppm): δ 21.0, 34.9 (d, J = 88.4 Hz), 57.9 (d, J = 92.9 Hz), 68.5 (d, J = 7.3 Hz), 125.7, 125.8, 126.6, 126.7, 127.2, 127.3, 127.3, 127.7, 128.1, 128.3, 128.3, 128.5, 128.6, 128.7, 128.7, 128.8, 129.2, 130.4, 130.4, 130.5, 130.6. 130.6, 133.2, 136.7, 136.8, 136.8, 137.8, 143.6. 31 P NMR (252MHz, CD2Cl2, ppm): δ 45.0. IR (KBr) 736.85, 1161.90, 1598.84, 3110.89 cm-1. LRMS (ESI) m/z 578.1 (M+Na+), HRMS (ESI) m/z 578.1170 (M+Na+), calc. for C32H30NO4PSNa 578.1549. The ee was determined by chiral HPLC; CHIRALCEL IA (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 16.4, 35.1min; 19.4, 28.8min. 122 Chapter (180f) (S)-benzyl benzyl((R)-furan-2-yl(4-methylphenylsulfonamido)methyl)phosphinate White solid. mp 190.1 – 194.8 oC. 71% yield, 94% ee of syn, 15% ee of anti. dr = 7:1. [α]30 D -11.0 (c 0.79, O H N S O O P O O CHCl3). 1H NMR (500MHz, CDCl3, ppm): δ 2.33 (s, 3H), 3.16 (d, 2H, J = 15.82Hz), 4.84(dd, 1H, J = 9.22, 14.63Hz), 4.91 (ddd, 2H, J = 6.43, 10.82, 22.81Hz), 5.70 (d, 1H, J = 9.04Hz), 6.09 (dt, 2H, J = 3.10, 3.10, 17.11Hz), 7.09-7.52 (m, 15H). 13C NMR (125MHz, CDCl3, ppm): δ 22.1, 35.1 (d, J = 89.3 Hz), 51.4 (d, J = 97.5 Hz), 68.7 (d, J = 7.3 Hz), 111.0, 111.1, 111.5, 127.7, 127.9, 127.9, 128.8, 129.1, 129.2, 129.3, 129.4, 130.0, 130.3, 130.4, 130.8, 130.9, 136.8, 137.7, 143.4, 143.4, 144.0, 146.6. 31 P NMR (252MHz, CDCl3, ppm): δ 43.7. IR (KBr) 732.31, 1157.32, 1602.33, 3063.42 cm-1. LRMS (ESI) m/z 494.2 (M-H+), HRMS (ESI) m/z 518.1170 (M+Na+), calc. for C26H26NO5PSNa 518.1162. The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); 123 Chapter hexane/2-propanol 90/10; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 57.9, 90.4min; 62.8, 83.6min. (180g) (S)-benzyl benzyl((R,E)-1-(4-methylphenylsulfonamido)-3-phenylallyl)phosphinate White solid. mp 146.7 – 148.9 oC. 92% yield, 90% ee of syn, 11% ee of anti. dr = 3:1. [α]30 D +19.6 (c 1.59, O H N S O O P O CHCl3). 1H NMR (500MHz, CDCl3, ppm): δ 2.19 (s, 3H), 3.24 (dt, 2H, J = 18.86, 18.86, 31.34Hz), 4.39(m, Ph 1H), 4.97 (m, 2H), 5.62 (d, 1H, J = 7.08Hz), 5.71 (ddd, 1H, J = 4.71, 5.89, 15.98Hz), 6.09 (dd, 1H, J = 3.82, 15.97Hz), 6.96-7.67 (m, 19H). 13C NMR (125MHz, CDCl3, ppm): δ 22.0, 35.0 (d, J = 89.3 Hz), 51.4 (d, J = 97.5 Hz), 68.7 (d, J = 7.3 Hz), 120.7, 120.7, 127.2, 127.9, 127.9, 128.1, 128.8, 128.9, 129.1, 129.1, 129.3, 129.4, 130.3, 130.6, 130.7, 130.9, 131.0, 135.6, 135.6, 136.2, 136.2, 136.8, 136.9, 138.4, 144.5. 31P NMR (252MHz, CDCl3, ppm): δ 45.7. IR (KBr) 741.93, 1162.49, 1598.83, 3085.54 cm-1. LRMS (ESI) m/z 554.1 (M+Na+), HRMS (ESI) m/z 554.1534 (M+Na+), calc. 124 Chapter for C30H30NO4PSNa 554.1525. The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 25.9, 60.2min; 28.0, 37.1min. (180i) (S)-benzyl ((R)-(4-methylphenylsulfonamido)(phenyl)methyl)(naphthalen-2-ylmethyl) phosphinate white solid. mp 141.4 – 143.5 oC. 92% yield, 94% ee of syn, 11% ee of anti. [α]28 D -47.5 (c 0.69, CHCl3). H O H N S O NMR (500MHz, CDCl3, ppm): δ 2.22 (s, 3H), 3.14 (d, O P O 2H, J = 15.15Hz), 4.82 (dd, 1H, J = 10.08, 15.75Hz), 4.91 (d, 2H, J = 7.57Hz), 6,44 (br, 1H), 6.85-7.79 (m, 21H). 13 C NMR (125MHz, CDCl3, ppm): δ 22.0, 35.4 (d, J = 88.4 Hz), 58.0 (d, J = 93.8 Hz), 68.9 (d, J = 7.3 Hz), 126.5, 126.8, 127.7, 127.9, 128.0, 128.2, 128.4, 128.8, 128.9, 128.9, 129.0, 129.1, 129.2, 129.7, 129.8, 129.9, 133.1, 133.1, 133.7, 134.0, 125 Chapter 134.0, 136.7, 136.8, 138.2, 143.7. 31P NMR (500MHz, CDCl3, ppm): δ 45.3. IR (KBr) 746.68, 1160.01, 1598.52, 3060.13 cm-1. LRMS (ESI) m/z 578.2 (M+Na+), HRMS (ESI) m/z 578.1525 (M+Na+), calc. for C32H30NO4PSNa 578.1525. The ee was determined by chiral HPLC; CHIRALCEL IC (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 21.5, 58.3min; 25.5, 28.4min. (180j) (S)-benzyl ((R)-(4-methylphenylsulfonamido)(phenyl)methyl)(4-(trifluoromethyl) benzyl)phosphinate White solid. mp 213.2 – 215.3 oC 92% yield, 94% ee of syn 20% ee of anti. dr = 16:1. [α]28 D -16.3 (c 1.67, CHCl3). H NMR (500MHz, CDCl3, ppm): δ 2.26 (s, 3H), 3.07 (t, 1H, J = 15.14Hz), 3.28 (t, 1H, J = 15.14Hz), 4.90 (dd, 1H, J = 10.09, 15.76Hz), 5.03 (d, 2H, J = 6.94Hz), 6.97 (br, 1H), 6.85-7.79 (m, 18H). 13C NMR (125MHz, CDCl3, ppm): δ 22.0, 31.5 (d, J = 89.3 Hz), 58.9 (d, J = 94.7 Hz), 69.3 (d, J = 7.3 Hz), 126.9 , 126 Chapter CF3 126.9, 127.2, 127.7, 127.8, 128.8, 128.8, 128.9, 128.9, 128.9, 129.1, 129.2, 129.2, 129.7, 129.8, 130.4, 132.3, O H N S O 132.9, 133.0, 133.6, 136.7, 138.2, 143.6. O P O (252MHz, CDCl3, ppm): δ 43.7. CDCl3, ppm): δ 16.7. 19 31 P NMR F NMR (282MHz, IR (KBr) 771.16, 1162.72, 1606.01, 3143.07 cm-1. LRMS (ESI) m/z 596.1 (M+Na+), HRMS (ESI) m/z 596.1248 (M+Na+), calc. for C29H27F3NO4PSNa 596.1243. The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; retention time: 16.2, 18.6min; 24.9, 31.6min. (180l) (S)-benzyl 4-methylbenzyl((R)-(4-methylphenylsulfonamido)(phenyl)methyl) phosphinate 127 Chapter White solid. mp 198.6 – 202.7 oC. 83% yield, 88% ee of syn, 15% ee of anti. dr = 5:1. 1H NMR (500MHz, H N O S CDCl3, ppm): δ 2.26 (s, 3H), 2.94 (s, 3H), 2.97 (d, 2H, O P J = 15.06Hz), 4.79(dd, 1H, J = 9.47, 15.34Hz), 4.96 O O (dd, 2H, J = 6.97Hz), 6.70 (br, 1H), 6.85-7.55 (m, 18H). 13C NMR (125MHz, CDCl3, ppm): δ 21.9 (d, J = 37.4 Hz), 35.0, 57.7 (d, J = 92.0 Hz), 68.7 (d, J = 7.3 Hz), 127.2, 127.2, 127.7, 127.7, 128.8, 128.8 128.9, 129.0, 129.1, 129.2, 129.8, 129.8, 129.9, 130.0, 130.7, 130.7, 130.8, 133.6, 136.8, 136.9, 137.4, 138.1, 143.8. 31 P NMR (252MHz, CDCl3, ppm): δ 45.6. IR (KBr) 728.69, 1160.67, 1598.89, 3105.75 cm-1. LRMS (ESI) m/z 542.1 (M+Na+), HRMS (ESI) m/z 542.1550 (M+Na+), calc. for C29H30NO4PSNa 542.1525 The ee was determined by chiral HPLC; CHIRALCEL ADH (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 0.5 ml/min; temp 25 °C; detection UV 210 nm; retention time: 17.5, 49.4min; 21.5, 23.8min. (180m) (S)-benzyl cinnamyl((R)-phenyl(phenylsulfonamido)methyl)phosphinate White solid. mp 185.0 – 188.9 oC. 82% yield, 82% ee O H N S O O P Ph O of syn. dr = 7:1. 1H NMR (500MHz, CDCl3, ppm): δ 2.59 (m, 2H), 4.89 (dd, 1H, J = 9.99, 15.39Hz), 5.09 (dd, 1H, J = 7.73, 11.62Hz), 5.26(dd, 1H, J = 7.43, 11.62Hz), 5.86 (dd, 1H, J = 6.92, 15.21Hz), 6.24 (m, 1H), 6.80 (br, 1H), 7.04-7.57 (m, 20H). 13C NMR (125MHz, CDCl3, ppm): δ 32.7 (d, J = 91.1 Hz), 57.8 (d, J = 92.9 Hz), 68.9 (d, J = 7.3 Hz), 117.5, 117.5, 127.0, 127.6, 128.4, 128.9, 128.9, 129.0, 129.1, 129.2, 129.2, 129.3, 132.8, 133.5, 136.6, 136.7, 136.9, 137.0, 137.2, 127.2, 141.3. 31P 128 Chapter NMR (252MHz, CDCl3, ppm): δ 46.1. IR (KBr) 738.59, 1160.18, 1598.74, 3089.81 cm-1. LRMS (ESI) m/z 540.1 (M+Na+), HRMS (ESI) m/z 540.1384 (M+Na+), calc. for C29H28NO4PSNa 540.1369. The ee was determined by chiral HPLC; CHIRALCEL IA (4.6 mm i.d. x 250 mm); hexane/2-propanol 70/30; flow rate 0.5 ml/min; temp 25 °C; detection UV 210 nm; retention time of syn: 13.9, 16.5 min. 129 Chapter References: Busacca, C. A.; Lorenz, J. C.; Gringerg, N.; Haddad, N.; Hrapchak, M.; Latli, B.; Lee, H.; Sabila, P.; Saha, A.; Sarvestani, M.; Shen, S.; Varsolona, R.; Wei, X.; Senanayke, C. H. Org. Lett. 2005, 7, 4277-4280. E. A. Boyd, A. C. Regan, Tetrahedron Lett. 1994, 35, 4223–4226. K. Afarinkia, H.-W. Yu, Tetrahedron Lett. 2003, 44, 781–783. Ye, W.; Leow, D.; Goh, S. L. M.; Tan, C.-T.; Chian, C.-H.; Tan, C.-H., Tetrahedron Lett. 2006, 47, 1007–1010. 130 [...]... 5.28-5.38 (m, 1H), 6.87-8. 74 (m, 18H) 13 C NMR (75 MHz, CDCl3, ppm): δ 44 .3 (d, J = 64. 7 Hz), 76.1 (d, J = 5.5 Hz), 1 24. 0, 1 24. 2, 1 24. 4, 1 24. 6, 125.6, 125.7, 126 .4, 126.6, 126.6, 127.0, 127.2, 127.5, 127.5, 127.9, 128.2, 128.3, 128.6, 129.2, 129 .4, 129.5, 129.6, 129.6, 130 .4, 130.6, 132.1, 132.2, 133.3, 133 .4, 133.6, 133.7, 133.8, 133.9, 133.9, 1 34. 1, 1 34. 2, 1 34. 3, 1 34. 3, 1 34. 4, 1 34. 4 31P NMR (121MHz, CDCl3,... = 5 .46 Hz), 58.0 (d, J = 76.5 Hz), 1 24. 7, 1 24. 8, 125.1, 125.2, 126.5, 126.8, 127.0, 127.1, 127 .4, 127 .4, 127.8, 128.1, 128.2, 128.7, 128.9, 129.3, 129 .4, 129.6, 129.7, 130.0, 132 .4, 132.5, 133.3, 133 .4, 133 .4, 133.5, 133.9, 133.9, 1 34. 1, 1 34. 1, 1 34. 3, 1 34. 4, 1 34. 5, 1 34. 5, 140 .0, 140 .2, 143 .0, 143 .6 31P NMR (252MHz, CDCl3, ppm): δ 39 .4 IR (KBr) 677.2, 11 54. 6, 1628.7, 3067.7 cm-1 LRMS (ESI) m/z 590.1... 138.0 31 P NMR (121MHz, CDCl3, ppm): δ - 34. 8 IR (KBr) 7 74, 15 04, 3050 cm-1 HRMS (ESI) m/z 44 0.1 348 (M+H+), calc for C28H24ClNP 44 0.1335 The ee of 147 was determined by converting back to 146 using H2O2 4. 6 Protocol for guanidinium salt catalyzed phospha-Mannich reactions and characterization of phospha-Mannich reaction products 4. 6.1 Protocol for phospha-Mannich reactions To a 5 ml RBF containing catalyst... MHz, CDCl3, ppm): δ 45 .1 (d, J = 64. 8 Hz), 76.2 (d, J = 5.5 Hz), 122 .4, 122.5, 1 24. 0, 1 24. 2, 1 24. 4, 1 24. 6, 125.6, 125.6, 126.1, 126.3, 126.5, 126.5, 126.9, 127 .4, 127.5, 127.9, 128.2, 128.8, 129.2, 130.6, 130.8, 130.9, 131.0, 131.0, 131.7, 132.3, 132 .4, 133.3, 133 .4, 133 .4, 133.6, 133.6, 133.8, 1 34. 1, 1 34. 2, 1 34. 2, 1 34. 4 31P NMR (121MHz, CDCl3, ppm): δ 36.6 IR (KBr) 770, 1158, 1 549 , 3052 cm-1 LRMS (ESI)... 96% ee [α] D -1 24. 6 (c 2.59, CHCl3) 1H NMR O P (300 MHz, CDCl3, ppm): δ 4. 94- 5.02 (m, 1H), 5.23-5.30 (m, 1H), NO2 5.36-5 .46 (m, 1H), 7.16-8.72 (m, 18H) NO2 13 C NMR (75 MHz, CDCl3, ppm): δ 45 .5 (d, J = 63.1 Hz), 75.6 (d, J = 4. 4 Hz), 123.0, 1 24. 1, 1 24. 3, 1 24. 4, 1 24. 5, 1 24. 6, 125 .4, 125 .4, 125.7, 126 .4, 126.5, 126.6, 127.0, 127.1, 127.5, 127.7, 128.1, 128.7, 129.2, 129 .4, 130.3, 130 .4, 132.1, 132.2,... δ 2. 24 (s, 3H), 5.88 (t, 1H, J = NHTs O P 10.72Hz), 6. 54- 8.55 (m, 21H) 13 C NMR (125MHz, CD2Cl2, O ppm): δ 22.0, 52 .4 (d, J = 75.6 Hz), 110.8, 111.1, 111.2, 125.0, 125.1, 125.5, 125.6, 126.5, 126.8, 127.1, 127.1, 127.2, 127.3, 127 .4, 127.6, 127.9, 128.0, 129.3, 129.6, 129.7, 130.3, 132.9, 133.0, 133.3, 133 .4, 133.9, 1 34. 0, 1 34. 1, 1 34. 2, 1 34. 3, 1 34. 6, 1 34. 7, 137.8, 139.9, 142 .7, 143 .4, 144 .0, 146 .3... 131.0, 132 .4, 132.5, 133.1, 133.2, 133.5, 133.6, 133.6, 133.7, O P Cl 133.9, 1 34. 0, 1 34. 1, 1 34. 1, 1 34. 3, 1 34. 4, 1 34. 7, 1 34. 8 31P NMR NO2 (121MHz, CDCl3, ppm): δ 38.9 IR (KBr) 7 64, 1161, 1565, 2923 cm-1 LRMS (ESI) m/z 48 6.1 (M+H+), HRMS (ESI) m/z 48 6.1 044 (M+H+), calc for C28H22ClNO3P 48 6.1026 The ee was determined by chiral HPLC; CHIRALCEL AD-H (4. 6 mm i.d x 250 mm); hexane/2-propanol 60 /40 ; flow rate... 3 .42 -3.50 (m, O P Cl NH2 105 Chapter 4 1H), 3.56-3.66 (m, 1H), 3.97 -4. 04 (m, 1H), 7. 04- 8.80 (m, 18H) 13C NMR (75 MHz, CDCl3, ppm): δ 43 .1, 49 .6 (d, J = 66 .4 Hz), 123.9, 1 24. 1, 1 24. 3, 1 24. 5, 126.0, 126.5, 126.6, 126.7, 127.0, 127 .4, 128.2, 128.5, 128.6, 128.7, 129.0, 129 .4, 129.7, 131.2, 131.3, 131 .4, 131.6, 131.9, 132.0, 132.8, 132.8, 133.3, 133.3, 133.5, 133.5, 133.6, 133.7, 133.8, 133.9, 1 34. 0, 1 34. 1... 133.9, 1 34. 1, 1 34. 2, 1 34. 4, 1 34. 4, 1 34. 5, 1 34. 9, 135.0, 147 .7 31 P NMR (121MHz, CDCl3, ppm): δ 37 .4 IR (KBr) 732, 1157, 1556, 30 64 cm-1 LRMS (ESI) m/z 49 7.1 (M+H+), HRMS (ESI) m/z 49 7.1291 (M+H+) calc for C28H22N2O5P 49 7.1266 The ee was determined by chiral HPLC; CHIRALCEL AD-H (4. 6 mm i.d x 250 mm); hexane/2-propanol 70/30; flow rate 1.0 ml/min; temp 25 °C; detection UV 210 nm; 99 Chapter 4 retention... 3H), 4. 88 (dd, 1H, J = 5.99, 10 .41 Hz), 5. 24 (br, 1H), 6.87-9.10(m, 18H) 13C NMR (75MHz, CDCl3, ppm): δ 22.1, 29.0 (d, J = 7.2 Hz), 38.8, 63.0 (d, J = 120.1 Hz), 1 24. 7, 1 24. 9, 125.0, 125.2, 126 .4, 126.8, 127.1, 128.0, 128.1, 130.0, 133.2, 133.3, 133.6, 1 34. 2, 1 34. 4, 1 34. 7, 143 .1 31P NMR (252MHz, CDCl3, ppm): δ 42 .9 IR (KBr) 702.1, 1157.7, 1639.1 cm-1 LRMS (ESI) m/z 5 64. 0 (M+Na+), HRMS (ESI) m/z 5 64. 1716 . δ 4. 9 4- 5 .02 (m, 1H), 5.2 3-5 .30 (m, 1H), 5.3 6-5 .46 (m, 1H), 7.1 6-8 .72 (m, 18H). 13 C NMR (75 MHz, CDCl 3 , ppm): δ 45 .5 (d, J = 63.1 Hz), 75.6 (d, J = 4. 4 Hz), 123.0, 1 24. 1, 1 24. 3, 1 24. 4,. 133.9, 1 34. 1, 1 34. 2, 1 34. 4, 1 34. 4, 1 34. 5, 1 34. 9, 135.0, 147 .7. 31 P NMR (121MHz, CDCl 3 , ppm): δ 37 .4. IR (KBr) 732, 1157, 1556, 30 64 cm -1 . LRMS (ESI) m/z 49 7.1 (M+H + ), HRMS (ESI) m/z 49 7.1291. ppm): δ 4. 8 2 -4 .90 (m, 1H), 5.1 2- 5.19 (m,1H), 5.2 6-5 .35 (m, 1H), 6.9 7-8 .76 (m, 18H). 13 C NMR (75 MHz, CDCl 3 , ppm): δ 44 .6 (d, J = 63.8 Hz), 76 .4 (d, J = 12.8 Hz), 1 24. 0, 1 24. 2, 1 24. 4, 125.6,