Asymmetric intramolecular hydroamination of allenes using mononuclear gold catalysts

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1 Supporting information Asymmetric intramolecular hydroamination of allenes using mononuclear gold catalysts Christophe Michon, a,b,c* Florian Medina, a,c Marc-Antoine Abadie, a,c Francine Agbossou- Niedercorn a,b,c* a Université Lille Nord de France, Lille, France b CNRS, UCCS UMR 8181, Villeneuve d Ascq, France c ENSCL, CCCF, (Chimie-C7) BP Villeneuve d Ascq, France Fax : , christophe.michon@ensc-lille.fr, francine.agbossou@enscl.fr I) General remarks. 2 II) Synthetic procedures for phosphoramidite ligands and characterizations 2 III) 3D simulations of pre-catalysts 7 IV) Study of potent non-linear effects 8 V) Characterization of other compounds. 9 VI) References. 14 VII) Determination of the stereochemistry of compound 2a by HPLC 15 VIII) HPLC chromatograms. 16 IX) 1 H, 13 C NMR spectra of isolated compounds. 22 X) HRMS of new compounds 49 1

2 I) General Remarks. All solvents were dried using standard methods and stored over molecular sieves (4 Å). All silver salts were weighted in a glovebox. All reactions were carried out under a dry nitrogen atmosphere and were repeated at least twice. Analytical thin layer chromatography (TLC) was performed on Merck pre-coated 0.20 mm silica gel Alugram Sil 60 G/UV 254 plates. Flash chromatography was carried out with Macherey silica gel (Kielselgel 60). 1 H (300 MHz), 13 C (75 MHz) and 31 P (121 MHz) spectra were acquired on a Bruker Avance spectrometer. Chemical shifts (δ) are reported downfield of Me 4 Si in ppm and coupling constants are expressed in Hz. 1,3,5-trimethoxybenzene and 1,2,4,5-tetrachlorobenzene were used as internal standards when needed. Infrared spectra were recorded on a ThermoScientific-Nicolet 6700 spectrometer; the samples being prepared with KBr powder. HPLC was performed on a Hitachi LaChromElite equipement with a micropump, a Peltier oven and a DAD detector. HRMS-ESI analyses were performed at CUMA-Pharm. Dept.-University Lille Nord de- France. Elemental analyses were performed at UCCS, University Lille Nord de France. AuS(Me) 2 Cl was prepared following related procedures. S1 BARF and TRIP silver salts were prepared as reported. S2,S3 Amino-allene substrates were prepared following reported procedures: 1a, S4 1b, S5 1c, S4 1d, S6 1e, S5 1f, S5 1g, S8 1h. S7 II) Synthetic procedures for phosphoramidite ligands and characterizations. II.a.) Synthetic procedures for phosphoramidite ligands. Compounds (R)-11 and (R)-10 are prepared according published procedures. S9 Compounds (R)-10, (R)-9 a and (R)-8 a are prepared according published procedures. S9 2

3 Compounds (R)-9 b and (R)-9 c are prepared according published procedures. S10 Compounds (R)-8 b and (R)-8 c are prepared according published procedures. S11 Compounds (R)-9 d and (R)-9 d are prepared according published procedures. S12 Compounds L are prepared according published procedures. S13 The same procedures are used for the synthesis of compound L 14 which has never been reported before. Same procedures were used for ligands (S,R,R)-L or (S,S,S)-L starting from (S)-8 a-d. 3

4 II.b.) Characterizations of phosphoramidite ligands. (R)-3,3 -diphenyl-2,2 -dihydroxy-1,1 -dinaphthyl S9 (R)-8 a 1 H NMR (300 MHz, CDCl 3 ): 5.37 (s, 2H), (m, 12H), 7.75 (d, J = 7 Hz, 4H), 7.94 (d, J = 8.5 Hz, 2H), 8.05 (s, 2H). (R)-3,3 -bis(1,1 -biphenyl)-2,2 -dihydroxy-1,1 -binaphthyl S14 (R)-8 b 1 H NMR (300 MHz, CDCl 3 ): 5.68 (s, 2H), (m, 12H), (d*, 4H), 7.79 (d, J = 8.4 Hz, 4H), 7.90 (d, J = 8.4 Hz, 4H), 8.00 (d, J = 7.9 Hz, 2H), 8.15 (s, 2H). 13 C NMR (75 MHz, CDCl 3 ): (C), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (C), (CH), (C), (C), (C), (C), (C). (R)-3,3 -bis(9-anthracenyl)-2,2 -dihydroxy-1,1 -binaphthyl S10 (R)-8 c 1 H NMR (300 MHz, CDCl 3 ): 5.26 (s, 2H), (m, 2H), (m, 10H), 7.65 (d*, 2H), 7.74 (d, 2H), (m, 4H), (m, 6H), 8.59 (s, 2H). 13 C NMR (75 MHz, CDCl 3 ): (C), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (CH), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C), (CH), (C), (C). (R)-3,3 -dibenzhydryl -2,2 -dihydroxyl-1,1 -binaphthalene S12 (R)-8 d 1 H NMR (300 MHz, CDCl 3 ): 5.38 (s, 2H), 6.12 (s, 2H), 7.15 (d, J = 8.2 Hz, 2H), (m, 26 H), 7.15 (d, J = 7.6 Hz, 2H). 13 C NMR (75 MHz, CDCl 3 ): 51.0 (CH), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C), (C). (R,R,R)-(-)-(2,6-diphenyl-3,5-dioxa-4-phospha-cyclohepta[2,1-a;3,4-a'] dinaphthalen-4-yl) bis(1-phenylethyl)amine (R,R,R)-L 11 S13 Isolated after flash chromatography with petroleum ether/toluene (1:1), Rf = 0.55, as a white solid (from 0.23 mmol, 0.17 mmol mg, 74%). 1 H NMR (300 MHz, CDCl 3 ): 1.16 (d, J = 7.0 Hz, 6H), 4.16 (m, 2H), 6.66 (d, J = 7.6 Hz, 4H), 6.95 (m, 6H), (m, 5H), (m, 9H), 7.80 (d, J = 8.4 Hz, 2H), (m, 3H), 8.06 (s, 1H). 4

5 31 P NMR (121.5 MHz, CDCl 3 ): C NMR (75 MHz, CDCl 3 ): 22.2 (CH 3 ), 22.3 (CH 3 ), 54.6 (CH), 54.9 (CH 3 ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (CH), (C), (C), (C), (C), (C). [ ] D 20 = -148 (CH 2 Cl 2, c 0.1 g / 100 ml) (R,R,R)-(-)-(2,6-bis[1,1 -biphenyl]-3,5-dioxa-4-phospha-cyclohepta[2,1-a;3,4-a'] S13 dinaphthalen-4-yl) bis(1-phenylethyl)amine (R,R,R)-L 12 Isolated after flash chromatography with petroleum ether/toluene (1:1), Rf = 0.6, as a white solid (from 0.15 mmol, mmol - 78 mg, 62%). 1 H NMR (300 MHz, CDCl 3 ): 1.20 (d, J = 7.0 Hz, 6H), (br s, 2H), 6.67 (d, J = 7.7 Hz, 4H), (m, 6H), (m, 2H), (m, 10H), (m, 10H), 7.87 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 8.07 (s, 1H), 8.13 (s, 1H). 31 P NMR (121.5 MHz, CDCl 3 ): C NMR (75 MHz, CDCl 3 ): 22.2 (CH 3 ), 22.3 (CH 3 ), 54.8 (CH), 55.0 (CH), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (CH), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C). [ ] 20 D = -338 (CH 2 Cl 2, c 0.1 g / 100 ml) (R,S,S)-(-)-(2,6-bis[1,1 -biphenyl]-3,5-dioxa-4-phospha-cyclohepta[2,1-a;3,4-a'] dinaphthalen-4-yl) bis(1-phenylethyl)amine (R,S,S)-L 12 S13 Isolated after flash chromatography with petroleum ether/toluene (1:1), Rf = 0.6, as a white solid (from 0.15 mmol, mmol - 66 mg, 52%). 1 H NMR (300 MHz, CDCl 3 ): 1.07 (d, J = 7.0 Hz, 6H), (br s, 2H), (m, 4H), (m, 6H), (m, 2H), (m, 11H), (m, 9H), 7.87 (t, J = 9.1 Hz, 2H), 8.04 (d, J = 6.4 Hz, 2H), 8.08 (s, 1H), 8.19 (s, 1H). 31 P NMR (121.5 MHz, CDCl 3 ): C NMR (75 MHz, CDCl 3 ): 29.9 (CH 3 ), 51.9 (CH), 52.1 (CH), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C). [ ] D 20 = -750 (CH 2 Cl 2, c 0.1 g / 100 ml) 5

6 (R,R,R)-(-)-(2,6-bis[9-anthracenyl]-3,5-dioxa-4-phospha-cyclohepta[2,1-a;3,4-a'] dinaphthalen-4-yl) bis(1-phenylethyl)amine (R,R,R)-L 13 S15 Isolated after flash chromatography with petroleum ether/toluene (1:1), Rf = 0.5, as a white solid (from mmol, mmol - 43 mg, 46%). NMR (300 MHz, CDCl 3 ): (-0.05)-0.25 (br s, 6H), (br s, 2H), 5.62 (d, J = 7.9 Hz, 4H), 6.39 (t, J = 7.9 Hz, 4H), 6.69 (t, J = 7.4 Hz, 2H), 7.02 (t*, 1H), 7.12 (t*, 1H), (m, 12H), 7.77 (d, J = 8.1 Hz, 1H), (m, 11H), 8.42 (s, 1H), 8.57 (s, 1H). 31 P NMR (121.5 MHz, CDCl 3 ): C NMR (75 MHz, CDCl 3 ): 21.5 (CH 3 ), 21.6 (CH 3 ), 54.5 (CH), 54.6 (CH), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (CH), (C), (C), (C), (CH), (C), (C), (C), (C). [ ] D 20 = -7 (CH 2 Cl 2, c 0.1 g / 100 ml) (R,S,S)-(-)-(2,6-bis[9-anthracenyl]-3,5-dioxa-4-phospha-cyclohepta[2,1-a;3,4-a'] dinaphthalen-4-yl) bis(1-phenylethyl)amine (R,S,S)-L 13 S15 Isolated after flash chromatography with petroleum ether/toluene (1:1), Rf = 0.5, as a white solid (from mmol, mmol -37 mg, 33%). 1 H NMR (300 MHz, CDCl 3 ): 0.04 (d, J = 6.8 Hz, 6H), (br s, 2H), 5.68 (d, J = 7.5 Hz, 4H), 6.27 (t, J = 7.9 Hz, 4H), 6.58 (t, J = 7.4 Hz, 2H), 7.02 (t*, 2H), (m, 12H), 7.60 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.9 Hz, 1H), (m, 7H), 8.11 (d, J = 8.4 Hz, 1H), 8.19 (s, 1H), 8.27 (d, J = 8.9 Hz, 1H), 8.48 (s, 1H), 8.56 (s, 1H). 31 P NMR (121.5 MHz, CDCl 3 ): C NMR (75 MHz, CDCl 3 ): 29.8 (CH 3 ), 51.0 (CH), 51.1 (CH), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (C), (CH), (C), (C), (C), (CH), (C), (C), (C), (C), (C). [ ] D 20 = -246 (CH 2 Cl 2, c 0.1 g / 100 ml) 6

7 III) 3D simulations of pre-catalysts. Gold(I) complexes issued from ligands (S,S,S)-L 12 and (S,S,S)-L 13 were drawn using Chem3DPro 12.0 software starting from an original X-Ray cif file of a related complex. S16 The resulting 3D drawing was then optimized by MM2 calculations. 3 views were selected to highlight the steric hindrance around the gold atom. Chart S1. 3D simulations of gold(i) complexes from ligands (S,S,S)-L 12 and (S,S,S)-L 13. 7

8 IV) Study of potent non-linear effects. The enantiomeric excess of the reaction product 2a (ee product) appeared to be proportional to the enatiopurity of the chiral ligand L 1 (ee ligand) suggesting the absence of nonlinear effects. Table S1. Study of potent non-linear effects in the conversion of reagent 1a to product 2a.. Entry Conversion (%) a ligand L 1 (S,R,R) Enantiopurity of (ee ligand %) Enantiomeric excess of product 2a b (ee product %) 1 > > > > a) Measured by 1 H NMR. b) Measured by HPLC at 200 nm. Figure S1. Enantioselectivity of product versus enantiopurity of ligand L 1 (S,R,R). 8

9 V) Characterization of other compounds. N-(2,2-diphenylhexa-4,5-dienyl)-4-methylbenzene sulfonamide (1b) S5 According a published procedure, S17 in an oven dried Schlenk flask, 4.65 mmol (1.14 g) of 2,2-diphenyl-4,5-hexadienylamine is dissolved in dry toluene. Then 10.2 mmol (0.85 ml) of dry pyridine and 5.1 mmol (975 mg) of p-toluenesulfonyl chloride are added under nitrogen. After 24 hours under stirring at room temperature, the solution is quenched with 10 ml of HCl aq (1 M). The layers are separated and the aqueous layer is extracted with Et 2 O (3x20 ml). Then the combined organic layers are dried over MgSO 4 and concentrated under vacuum. After flash chromatography using (8/2) petroleum ether/ethylacetate (Rf = 0.45) and evaporation of solvents, compound 1b is obtained as a white solid (1.20 g, 60%). 1 H NMR (300 MHz, CDCl 3 ): δ= 2.42 (s, 3H), 2. (dt, J = 7.7 Hz and J = 2.4 Hz, 2H), 3. (d, J = 6.8 Hz, 2H), 3.85 (t, J = 6.8 Hz, 1H), (m, 1H), (m, 2H), 7.05 (dd*, 4H), (m, 8H), 7.59 (d, J = 8.4 Hz, 2H). 13 C NMR (75 MHz, CDCl 3 ): δ= 21.6 (CH 3 ), 37.0 (CH 2 ), 49.6 (CH 2 ), 50.1 (C), 74.2 (CH 2 ), 84.7 (CH), (2 CH), (2 CH), (4 CH), (4 CH), (2 CH), (C), (C), (2 C), (C). HMRS (ESI) m/z calcd for C 25 H 26 NO 2 S : [MH + ], found : Benzyl-4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (2a) S4 Isolated after flash chromatography with petroleum ether/ethylacetate (8/2), Rf = 0.6, as a colorless oil. 1 H NMR (300 MHz, CDCl 3 ) ratio of rotamers (1:1): (m, 1H), (m, 1H), 3.71 (dd, J = 7.3 Hz and J = 11.5 Hz, 1H), (m, 1H), [4.61 (d, J = 11.3 Hz), 4.77 (d, J = 11.6 Hz), 1:1, 1H], (m, 4 H), (m, 1H), (m, 15H). 13 C NMR (75 MHz, CDCl 3 ) ratio of rotamers (1:1): [44.7 and 44.7, (1:1), CH 2 ], [52.7 and 53.1, (1:1)], 56.2 (CH 2 ), [59.1 and 59.5, (1:1), CH], 66.9 (CH 2 ), [115.2 and 115.8, (1:1), CH 2 ], 126.5, 126.7, 126.9, 127.6, 127.8, 128.1, 128.2, 128.4, 128.6, 128.7, 136.9, 137.1, [139.2 and 138.5, (1:1), CH], (2 C), [154.8 and 155.6, (1:1), C]. [ ] D 20 = +61 (CH 2 Cl 2, c 0.6 g / 100 ml, for (R)-enantiomer at 77% ee ). Enantiomeric excess (ee) is measured by HPLC using Daicel Chiralpak TM AD CSP, at 25 C, with (75/25) nhexane/iproh, 0.5 ml/min, λ = 220 nm, t R (minor)= 15.5 min. and t R (major)= 18.6 min. 4,4-diphenyl-1-p-toluene-sulfonyl-2-vinylpyrrolidine (2b) S5 Isolated after flash chromatography with petroleum ether/ethylacetate (8/2), Rf = 0.7, as a white solid. 1 H NMR (300 MHz, CDCl 3 ): (m, 4H), 2.79 (dd, J = 7.2 Hz and J = 12.7 Hz, 1H), (m, 3H), 5.02 (d, J = 10.0 Hz, 1H), 5.15 (d, J = 17.3 Hz, 1H), (m, 1H), (m, 12H), 7.63 (d, J = 8.2 Hz, 2H). 9

10 13 C NMR (75 MHz, CDCl 3 ): 21.6 (CH 3 ), 45.5 (CH 2 ), 52.6 (C), 58.3 (CH 2 ), 62.1 (CH), (CH 2 ), (CH), (2 CH), (CH), (2 CH 2 ), (2 CH), (2 CH), (2 CH), (2 CH), (C), (CH), (C), (C), (C). HMRS (ESI) m/z calcd for C 25 H 26 NO 2 S : [MH + ], found : [ ] D 20 = +11 (CH 2 Cl 2, c 0.58 g / 100 ml, for 32% ee). Enantiomeric excess (ee) is measured by HPLC using Daicel Chiralpak TM IA CSP, at 25 C, with (95/5) nhexane/iproh, 0.5 ml/min, λ = 220 nm, t R (minor)= 39.1 min. and t R (major)= 41.3 min. Tert-butyl-4,4-diphenyl-2-vinylpyrrolidine-1-carboxylate (2c) S4 Isolated after flash chromatography with petroleum ether/ethylacetate (9/1), Rf = 0.8, as a colorless oil. 1 H NMR (300 MHz, CDCl 3 ) ratio of rotamers (~ 2:1): [1.38 (s), 1.47 (s), ~1:2, 9H], (m, 1H), (m, 1H), (m, 1H), [3.90 (q, J = 8.0 Hz), 4.08 (q, J = 8.0 Hz), 1H], [4.52 (d, J = 11.2 Hz), 4.70 (d, J = 13.2 Hz), 1H], (m, 2 H), (m, 1H), (m, 10H). 13 C NMR (75 MHz, CDCl 3 ) ratio of rotamers: [28.7 and 28.9, 3 CH 3 ], [45.3 and 46.1, CH 2 ], [53.0 and 53.2, C], [55.8 and 56.7, CH], [59.3 and 59.5, CH 2 ], 80.1 (CH), [115.1 and 115.2, CH 2 ], [126.6 and 126.7, 2 CH], [126.8 and 127.0, 4 CH], [127.1 and 128.8, 4 CH], [139.3 and 139.9, CH], [145.3 and 145.7, 2 C], [154.7 and 155.3, C]. [ ] D 20 = -51 (CH 2 Cl 2, c 0.14 g / 100 ml, at 42% ee). Enantiomeric excess (ee) is measured by HPLC using Daicel Chiralpak TM AD CSP, at 25 C, with (99/1) n-hexane/iproh, 0.5 ml/min, λ = 200 nm, t R (major)= 14.4 min. and t R (minor)= 16.7 min. 1-(2,2-Diphenylhexa-4,5-dienyl)-3-phenylurea (2d) S6 Isolated after flash chromatography with petroleum ether/ethyl acetate (1/1), Rf = 0.5, as a white solid. 1 H NMR (300 MHz, CDCl 3 ): 2.59 (dd, J = 9.4 Hz and J = 12.1 Hz, 1H), 2.86 (q, J = 8.3 Hz, 1H), 3.70 (d, J = 12.1 Hz, 1H), 4.05 (q, J = 8.5 Hz, 1H), 5.00 (d, J = 11.6 Hz, 1H), 5.29 (d, J = 10.2 Hz, 1H), 5.42 (d, J = 13.3 Hz, 1H), 5.95 (m, 1H), 6.72 (s, 1H), 7.03 (dt, J = 1.2 Hz and J = 7.4 Hz, 1H), (m, 12H), 7.42 (d, J = 9.6 Hz, 2H). 13 C NMR (75 MHz, CDCl 3 ): 46.2 (CH 2 ), 51.8 (C), 55.4 (CH), 59.7 (CH 2 ), (CH 2 ), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (CH), (C), (C), (C), (C). [ ] 20 D = -43 (CH 2 Cl 2, c 0.18 g / 100 ml, at 28% ee). Enantiomeric excess is measured by HPLC using Daicel Chiralpak TM AD CSP, at 25 C, with (75/25) nhexane/iproh, 0.5 ml/min, λ = 220 nm, t R (major)= 15.2 min. and t R (minor)=18.8 min. 10

11 1-(N-Benzyl)-4,4-diphenyl-2-vinylpyrrolidine (2e) S5 Isolated after flash chromatography with petroleum ether/ethylacetate as a colorless oil. 1 H NMR (300 MHz, CDCl 3 ): 2.44 (dd, 1H, J= 8.0), 2.86 (d, 1H, J= 9.9), 2.95 (dd, 1H, J= 7.8), 3.26 (m, 2H), 3.68 (d, 1H, J= 9.6), 4.12 (d, 1H, J= 13.2), 5.18 (d+d, 2H, J= 10.2, J= 17.4), 5.83 (m, 1H), 7.24 (m, 15H). 13 C NMR (75 MHz, CDCl 3 ): 46.6, 53.1, 57.8, 65.6, 68.2, 116.7, 125.6, 126.0, 126.9, 127.3, 127.6, 127.9, 128.3, 128.7, 140.0, 140.7, 148.5, Enantiomeric excess is measured by HPLC using Daicel Chiralpak TM AD-H CSP, at 25 C, with (99/1) nhexane/iproh, 0.5 ml/min, λ = 220 nm, t R = 12.2 min. and t R = 12.9 min. Ee was too low to measure any [ ] 20 D. Benzyl-2-(2-methylprop-1-en-1-yl)-4,4-diphenylpyrrolidine-1-carboxylate (2f) S8 Isolated after flash chromatography with petroleum ether/ethylacetate (1/1), Rf = 0.5, as a colorless oil 1 H NMR (300 MHz, CDCl 3 ) as a mixture of 2 rotamers: 1.38 (s; 3H), 1.62 (s, 3H), 1.69 (d, 3H), 2.35 (m, 1H), 2.77 (m, 1H), 3.67 (dd, 1H, J= 6.6 Hz), 4.33 (m, 1H), 4.65 (dd, 1H, J= 9.9 Hz), 5.04 (m, 2H), 5.24 (dd, 1H, J= 12.6 Hz), 7.19 (m, 15H). 13 C NMR (75 MHz, CDCl 3 ) as mixture of 2 rotamers: [17.9, 18.3], [25.8, 26.0], [44.9, 45.6], [52.6, 53.1], [54.6, 55.1], [56.0, 56.1], [66.8, 66.9], 125.8, [126.4, 126.5], [126.6, 126.7], 126.9, [127.7, 127.8], [128.1, 128.2], 128.4, [128.6, 128.7], 128.8, [133.3, 134.1], 137.0, [145.1, 145.8], [155.4, 158.0] (CO). [ ] 20 D = -17 (CH 2 Cl 2, c 0.17 g / 100 ml, at 22% ee). Enantiomeric excess is measured by HPLC using Daicel Chiralpak TM IA CSP, at 25 C, with (95/5) nhexane/iproh, 1 ml/min, λ = 220 nm, t R (major) = 13.1 min. and t R (minor) = 17.1 min. Benzyl-3-vinyl-2-aza-spiro[4.5]decane-2-carboxylate (2h) S7 Isolated after flash chromatography with petroleum ether/ethylacetate (1/1), Rf = 0.5, as a colorless oil. 1 H NMR (300 MHz, CDCl 3 ): 1.43 (m, 11H), 2.02 (dd, 1H, J= 7.9 Hz), 3.08 (d, 1H, J= 11.0 Hz), 3.60 (dd, 1H, J= 10.5 Hz), 4.32 (m, 1H), 5.11 (m, 4H), 5.79 (m, 1H), 7.33 (m, 5H). 13 C NMR (75 MHz, CDCl 3 ) as a mixture of 2 rotamers: 23.1, 23.8, 26.2 (2C), 35.0, 36.5, [43.9, 44.9], 57.2, [58.9, 59.4], [66.7, 66.8], [114.0, 114.6], (4C Ar ), [128.4, 128.5] (1C Ar ), [137.0, 137.2] (1C Ar ), [139.5, 140.2], [155.3, 155.7] (CO). Enantiomeric excess (ee) is measured by HPLC using Regis (S,S)-Whelk 01 TM CSP, at 25 C, with (90/10) nhexane/iproh, 1 ml/min, λ = 220 nm, t R (minor)=17.7 min. and t R (major)= 31.0 min. Ee was too low to measure any [ ] 20 D. 11

12 (1R,2R)-N 1,N 2 -bis(2-methoxyphenyl)-1,2-diphenylethane-1,2-diamine (13) S18 O NH HN O In a first Schlenk tube, (+/-)-BINAP (0.24 mmol, 147 mg) is disposed along with a stirring bar. In a glovebox, Pd 2 dba 3 (0.12 mmol, 108 mg) and NaOt-Bu (3.40 mmol, 325mg) are added to that first Schlenk tube. After addition of toluene (3 ml), the resulting mixture is stirred at room temperature for 1h. In a glovebox, (1S,2S)-1,2-diphenylethane- 1,2-diamine (1.12 mmol, 250 mg) are disposed in a second Schlenk tube. Under nitrogen, toluene (2 ml) is added to that Schlenk and the resulting solution is transferred to the first Schlenk tube by cannula. After stirring for 30 minutes, 1-bromo-2-methoxybenzene (2.90 mmol, 550 mg) are finally added and the resulting mixture is heated at 120 C for 19 h. Afterwards, the reaction is filtered through a pad of Celite using ethylacetate as a solvent and solvents were evaporated under vacuum. The residue was purified by flash chromatography on silica gel using a (8/2) petroleum ether / ethylacetate mixture. After evaporation of solvents, a white solid is obtained (50 mg, 0.12 mmol, quantitative). NMR 1 H (300 MHz, CDCl 3 ) : 3.83 (s, 6H 8 ), 4.58 (s, 2H 9 ), 6.31 (m, 1H Ar ), 6.65 (m, 8H 4,5,6,7 ), 7.15 (m, 9H Ar ). NMR 13 C (75 MHz, CDCl 3 ) : 56.1 (2CH 3, C 8 ), 64.5 (2CH, C 9 ), (2CH Ar, C 7 ), (2CH Ar, C 4 ), (2C, C 2 ), (2CH Ar, C 5 ), (2CH Ar, C 6 ), (2CH Ar, C 13 ), (4CH Ar, C 11 ou 15 ), (4CH Ar, C 11 ou 15 ), (4CH Ar, C 14,12 ), (2C, C 10 ), (2C, C 3 ). (4R,5R)-1,3-bis(2-methoxyphenyl)-4,5-diphenylimidazol-3-inium tetrafluoroborate (14) S19 In a Schlenk tube are disposed and dried a stirring bar, diamine 13 (200 mg, 0.47 mmol) and NH 4 BF 4 (49 mg, 0,47 mmol). Under nitrogen, triethylorthoformate (2 ml) are added and the resulting mixture is stirred for 18 h at 135 C. After evaporation under vacuum of all the volatiles, the residue is purified by flash chromatography on silica gel using a 20% acetone gradient in petroleum ether. After evaporation of solvents, a beige pale solid is recovered (39 mg, 0.08 mmol, 78 %). NMR 1 H (300 MHz, CDCl 3 ) : 3.97 (s, 6H 8 ), 5.77 (s, 2H 9 ), (m, 4H 5,7 ), (m, 4H 4,6 ), (m, 10H 11,12,13,14,15 ), 8.98 (s, 1H 1 ). NMR 13 C (75 MHz, CDCl 3 ) : 56.2 (2CH 3, C 8 ), 75.2 (2CH, C 9 ), (2CH Ar, C 7 ), (2CH Ar, C 4 ), (2C, C 2 ), (2CH Ar, C 5 ), (2CH Ar, C 6 ), (2CH Ar, C 13 ), (4CH Ar, C 11,15 ), (4CH Ar, C 14,12 ), (2C, C 10 ), (2C, C 3 ), (CH, C 1 ). (4R,5R)-1,3-Bis(2-methoxyphenyl)-4,5-diphenyl-imidazolin-2-ylidene gold(i) chloride (3) S19 In a Schlenk tube are disposed and dried a stirring bar, imidazolinium 14 (200 mg, 0.38 mmol), Ag 2 O (44 mg, 0.19 mmol) and (Me) 4 NCl (63 mg, 0,57 mmol). Under nitrogen, dry acetonitrile (2mL) is added and the reaction is stirred at room temperature overnight (12h) protected from light. Afterwards, the mixture is filtered through a pad of Celite using acetonitrile as solvent and the resulting solution is concentrated under vacuum. Under nitrogen, AuClS(Me) 2 (113 mg, 0.38 mmol) dissolved in dichloromethane is then added and the reaction is stirred overnight at 50 C. Afterwards, the mixture is filtered through a pad of Celite using acetonitrile as solvent and the resulting solution is evaporated under vacuum. The solid residue is purified by flash chromatography on silica gel using a 6/4 mixture of petroleum ether and acetone. After evaporation of solvents under vacuum, a beige solid is recovered (95 mg, 0.14 mmol, 37%). 12

13 NMR 1 H (300 MHz, CDCl 3 ) : 3.93 (s, 6H 8 ), 5.41 (s, 2H 9 ), (m, 2H 5 ), 6.89 (d, J = 8.3, 2H 7 ), (m, 4H 6,4 ), (m, 10H 11,12,13,14,15 ). NMR 13 C (75 MHz, CDCl 3 ) : 55.7 (2CH 3, C 8 ), 75.2 (2CH, C 9 ), (2CH Ar, C 7 ), (2CH Ar, C 4 ), (2CH Ar, C 5 ), (2C, C 2 ), (2CH Ar, C 6 ), (2CH Ar, C 13 ), (4CH Ar, C 15,11 ), (4CH Ar, C 14,12 ), (2C, C 10 ), (2C, C 3 ), (C Au, C 1 ). (1S,2S)-N 1,N 2 -dibenzhydryl-1,2-diphenylethane-1,2-diamine (15) S20,S21 NH HN In a Schlenk tube, are disposed and dried a stirring bar, bromodiphenylmethane (256 mg, 1 mmol), sodium carbonate (199 mg, 1.9 mmol) and (1S,2S)-1,2-diphenylethane-1,2-diamine (100 mg, 0.5 mmol). Under nitrogen, DMPU (1.4 ml) is added and the resulting mixture is stirred at 120 C for 2 h. Afterwards, brine (5 ml) is added and the liquid is extracted with ethylacetate (3*5 ml). Organic phases are subsequently washed with water (2*5 ml), brine (2*5 ml), dried over MgSO 4 and evaporated under vacuum. The residue is purified by flash chromatography on silica gel using a 9/1 mixture of petroleum ether and ethylacetate. After evaporation of solvents under vacuum, compound 15 is recovered as a solid is recovered (184 mg, 0.34 mmol, 72 %). NMR 1 H (300 MHz, CDCl 3 ) : 2.01 (s, 2H 11 ), 3.66 (s, 2H 1 ), 4.42 (s, 2H 6 ), (m, 30H Ar ). NMR 13 C (75 MHz, CDCl 3 ) : 63.2 (2CH, C 6 ), 65.4 (2CH, C 1 ), (4CH Ar, C 10 ), (2CH Ar, C 5 ), (4CH Ar, C 3 ), (8CH Ar, C 8 ), (4CH Ar, C 4 ), (8CH Ar, C 9 ), (2C, C 2 ), (4C, C 7 ). (4S,5S)-1,3-dibenzhydryl-4,5-diphenylimidazol-3-inium tetrafluoroborate (16) S19,S20 In a Schlenk tube are disposed and dried a stirring bar, diamine 15 (222 mg, 0.4 mmol) and NH 4 BF 4 (47 mg, 0.44 mmol). Under nitrogen, triethylorthoformate (2ml) is introduced and the reaction is stirred at 135 C overnight (12h). Afterwards, the volatiles are evaporated under vacuum and the solid residue is purified by flash chromatography on silica gel using a 20% acetone gradient in petroleum ether. After evaporation of solvents under vacuum, a pink pale solid is recovered (233 mg, 0.36 mmol, 89%). NMR 1 H (300 MHz, CDCl 3 ) : 5.06 (s, 2H 1 ), 5.65 (s, 2H 6 ), (m, 4H Ar ), (m, 17H Ar ), (m, 10H Ar ). NMR 13 C (75 MHz, CDCl 3 ) : 65.6 (2CH, C 1 ), 74.1 (2CH, C 6 ), (CH Ar ), (CH Ar ), (CH Ar ), (CH Ar ), (CH Ar ), (CH Ar ), (CH Ar ), (CH Ar ), (CH Ar ), (2C, C 2 ), 134.1, (4C, C 7 ), (CH, C 11 ). (4S,5S)-1,3- dibenzhydryl 4,5-diphenyl-imidazolin-2-ylidene gold(i) chloride (5) S19,S20 In a Schlenk tube are disposed and dried a stirring bar, imidazolinium 16 (130 mg, 0.2 mmol), Ag 2 O (24 mg, 0.1 mmol) and (Me) 4 NCl (33 mg, 0.3 mmol). Under nitrogen, dry acetonitrile (2mL) is added and the reaction is stirred at room temperature overnight (12h) protected from light. Afterwards, the mixture is filtered over Celite using acetonitrile as solvent and the resulting solution is concentrated under vacuum. Under nitrogen, AuClS(Me) 2 (60 mg, 0.2 mmol) dissolved in dichloromethane is then added and the reaction is stirred overnight (12h) at 50 C. Afterwards, the mixture is filtered through Celite using acetonitrile as solvent and the resulting solution is evaporated under vacuum. The solid residue is purified by flash 13

14 chromatography on silica gel using a (6/4) mixture of petroleum ether and acetone. After evaporation of solvents under vacuum, a white solid is recovered (67 mg, 0.09 mmol, 42%). NMR 1 H (300 MHz, CDCl 3 ) : 4.62 (s, 2H 11 ), 5.87 (s, 2H 2 ), 7.07 (m, H Ar ), 7.33 (m, H Ar ). NMR 13 C (75 MHz, CDCl 3 ) : 66.5 (2CH, C 2 ), 74.1 (2CH, C 11 ), (4CH Ar ), (2CH Ar ), (4CH Ar ), (4CH Ar ), (4CH Ar ), (4CH Ar ), (2CH Ar ), (2CH Ar ), (4CH Ar ), (2C, C 12 ), 138.1, (2C, C 7,3 ), (CAu, C 1 ). VI) References (S1) Hooper, T. N.; Butts, C. P.; Green, M.; Haddow, M. F.; McGrady, J. E.; Russel, C. A. Chem. Eur. J. 2009, 15, (S2) (a) Buschmann, W. E.; Miller, J. S. Inorganic Syntheses 2002, 33, 83-84; (b) Yakelis, N. A.; Bergman, R. G. Organometallics 2005, 24, ; (c) Brookhart, M.; Grant, B.; Volpe, A. F. Organometallics 1992, 11, (S3) (a) Klussmann, M.; Ratjen, L.; Hoffmann, S.; Wakchaure, V.; Goddard, R.; List, B. Synlett 2010, ; (b) Hamilton, G. L.; Kang, E. J.; Mba, M; Toste, F. D. Science 2007, 317, (S4) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, (S5) (a) Arbour, J. L.; Rzepa, H. S.; Contreras-Garcia, J.; Adrio, L. A.; Barreiro, E. M.; Hii, K. K. Chem. Eur. J. 2012, 18, (b) Mukherjee, P.; Widenhoefer, R. A. Angew. Chem. Int. Ed. 2012, 51, (S6) Li, H.; Lee, S. D.; Widenhoefer, R. A. J. Organomet. Chem. 2011, 696, (S7) Teller, H.; Corbet, M.; Mantilli, L.; Gopakumar, G.; Goddard, R.; Thiel, W.; Fürstner, A. J. Am. Chem. Soc. 2012, 134, (S8) Zhang, Z.; Bender, C. F.; Widenhoefer, R. A. Org. Lett. 2007, 9, (S9) Wu, T. R.; Shen, L.; Chong, J. M. Org. Lett. 2004, 6, (S10) Singh, R.; Czekelius, C.; Schrock, R. R.; Müller, P.; Hoveyda, A. H. Organometallics 2007, 26, (S11) Storer, R. I.; Carrera, D. E.; Ni, Y.; MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, (S12) Zhang, Y. L.; Zhang, F.; Tang, W. J.; Wu, Q. L.; Fan, Q. H. Synlett 2006, 8, (S13) Mercier, A.; Urbaneja, X.; Yeo, W. C.; Chaudhuri, P. D.; Cumming, G. R.; House, D.; Bernardinelli, G.; Kündig, E. P. Chem. Eur. J. 2010, 16, (S14) Wipf, P.; Jung, J. K. J. Org. Chem. 2000, 65, (S15) Alonso, I.; Trillo, B.; Lopez, F.; Montserrat, S.; Ujaque, G.; Castedo, L.; Lledos, A.; Mascarenas, J. L. J. Am. Chem. Soc. 2009, 131, (S16) Teller, H.;,, tn, Angew. Chem., Int. Ed. 2010, 49, (see file CCDC ). These data can be obtained free of charge from The Cambridge Crystallographic Data Centre : (S17) Zeng, W.; Chemler, S. R. J. Am. Chem. Soc. 2007, 129, (S18) (a) Cabanal-Duvillard, I.; Mangeney, P. Tetrahedron Lett. 1999, 40, (b) Kumar, A.; Samuelson, A. G. Eur. J. Org. Chem. 2011, (S19) (a) Matsumoto, Y.; Yamada, K. I.; Tomioka, K. J. Org. Chem. 2008, 73, (b) Matsumoto, Y.; Selim, K. B.; Nakanishi, H.; Yamada, K. I.; Yamamoto, Y.; Tomioka, K. Tetrahedron Lett. 2010, 51, (S20) Selim, K. B.; Matsumoto, Y.; Yamada, K.; Tomioka, K. Angew. Chem. Int. Ed. 2009, 48, (S21) Siu, T.; Li, W.; Yudin, A. K. J. Comb. Chem. 2001, 3, (S22) Zhang, Z.; Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc. 2007, 129,

15 VII) Determination of the stereochemistry of compound 2a. The stereochemistry of 2a was determined by HPLC by comparison with previous work. S22 15

16 VIII) HPLC chromatograms. 16

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22 IX) 1 H, 13 C NMR spectra of isolated compounds. 22

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49 X) HRMS of new compounds. 49

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