Transfer of axial chirality through the nickel-catalyzed hydrocyanation of chiral allenes

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1 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 7 Electronic supplementary information for Transfer of axial chirality through the nickel-catalyzed hydrocyanation of chiral allenes Yuka Amako, Shigeru Arai*, and Atsushi Nishida Graduate School of Pharmaceutical Sciences, Chiba University -8- Inohana, Chuo-ku, Chiba , Japan araisgr@chiba-u.jp List of Contents A. General remarks (Page ) B. Synthesis of optically active allenes (Page -4) C. General Procedure for ydrocyanation (Page 5-8) D. Determination of absolute stereochemistry of (R)-4a and (S)-4d (Page 8) E. Examination of time course (Page 9) F. Examination of racemization (Page 9) G. References (Page 9). PLC charts (Page -4) I. and 3 C NMR charts for all new compounds (page 5-)

2 A. General remarks All reactions were performed with dry solvents and reagents were purified by the usual methods. Reactions were monitored by thin-layer chromatography carried out on.5 mm Merck silica gel plates (6F-54). Column chromatography was performed with silica gel (Fuji Silysia, PSQ-6B). IR spectra were recorded on a JASCO FT/IR-3 Fourier transform spectrophotometer. NMR spectra were recorded on JEOL JMN-ECS-4, ECP-4, ECA-6 and ECP-6 at 4 and 6 Mz for NMR and at and 5 Mz for 3 C NMR, with calibration using residual undeuterated solvent as an internal reference. Mass spectra were recorded using ESI mode with JEOL JMS-TLP and APPI mode with Thermo Fisher Exactive. The enantiomeric excess was determined by PLC analysis using JASCO PLC LC-Plus series (PU-89, CO-65, UV-75). Optical rotations were measured using JASCO P- and P- Polarimeter. X-ray crystal data were collected with Rigaku VariMax with RAPID diffractometer at 8± C using filtered Cu-Kα radiation. B. Synthesis of optically active allenes Optically active allenes were synthesized according to the reported procedure. Spectral data of (R)-3a,3d-g and 3k were identical to the literature data. (R)-(4,4-dimethylpenta-,-dien--yl)benzene ((R)-3a) 3 PLC conditions: Chiralcel OJ-, hexane (%), f:.5ml/min, tr:.,.7 min (99% ee). t-bu (R)--(4,4-dimethylpenta-,-dien--yl)-4-(trifluoromethyl)benzene ((R)-3b) CF 3 t-bu Colorless oil. NMR (CDCl 3, 6 Mz) δ:.3 (s, 9), 5.64 (d,, J = 6. z), 6. (d,, J = 6. z), 7.37 (d,, J = 7.8 z), 7.53 (d,, J = 7.8 z); 3 C NMR (CDCl 3, Mz) δ: 3., 3.9, 95.4, 7.4, 4.3 (q, J = 7. z), 5.5 (q, J = 4.4 z), 6.4, 8.5 (q, J = 3.7 z), 39., 3.5; IR (ATR) ν: 96, 949 cm - ; RMS (APPI) m/z calcd for C 4 5 F 3 [M] + 4., found 4.6; [α] 5 D = (c =.4, CCl 3, 98% ee); PLC conditions: Chiralcel OJ-, hexane (%), f:.5 ml/min, tr: 9., 9.4 min (98% ee). (R)--(4,4-dimethylpenta-,-dien--yl)-4-methoxybenzene ((R)-3c) OMe t-bu Colorless oil. NMR (CDCl 3, 4 Mz) δ:. (s, 9), 3.79 (s, 3), 5.55 (d,, J = 5.6 z), 6.5 (d,, J = 5.6 z), 6.84 (d,, J = 8.4 z), 7. (d,, J = 8.4 z); 3 C NMR (CDCl 3, Mz) δ: 3.3, 3.7, 55.3, 95.6, 6.9, 4., 7.4, 7.6, 58.5,.7; IR (ATR) n: 57, 947 cm - ; RMS (APPI) m/z calcd for C 4 9 O [M+] , found 4.45; [α] 5 D = -48. (c =., CCl 3, 88% ee); PLC conditions: Chiralcel OJ-, hexane/i-pro = 99:, f:.5 ml/min, tr:.7, 4.5 min (88% ee).

3 (R)-(3-cyclohexylpropa-,-dien--yl)benzene ((R)-3d) PLC conditions: Chiralcel IB, hexane (%), f:.5 ml/min, 9.6,.6 min (97% ee). Cy (R)--(3-cyclohexylpropa-,-dien--yl)-4-(trifluoromethyl)benzene ((R)-3e) CF 3 Cy [α] 4 D = -3. (c =., CCl 3, 98% ee); PLC conditions: Chiralcel OD-, hexane (%), f:. ml/min, tr: 5.4, 6. min (97% ee) (R)--(3-cyclohexylpropa-,-dien--yl)-4-methoxybenzene ((R)-3f) OMe Cy [α] 6 D = (c =.6, CCl 3, 85% ee); PLC conditions: Chiralcel OD-, hexane/i-pro = 99:, f:. ml/min, tr: 4.7, 5. min (85% ee). (R)--bromo-4-(3-cyclohexylpropa-,-dien--yl)benzene ((R)-3g) Br Cy [α] 4 D = (c =.8, CCl 3, 98% ee); PLC conditions: Chiralpak IB, hexane (%), f:.5 ml/min, tr: 9.,.4 min (98% ee) (R)--(3-cyclohexylpropa-,-dien--yl)-3-(trifluoromethyl)benzene ((R)-3h) CF 3 Cy Colorless oil. NMR (CDCl 3, 4 Mz) δ: (m, 5), (m, ), (m, ), (m, ),.-. (m, ), 5.63 (dd,, J = 6.4, 6.4 z), 6.8 (dd,, J = 6.4, 3. z), (m, 3), 7.5 (s, ); 3 C NMR (CDCl 3, 5 Mz) δ: 5.97, 6.4, 33., 37.5, 94.6,.8, 3. (J =.9 z), 3. (J =.9 z), 4. (J = 7.4 z), 8.9, 9.5, 3. (J = 33. z), 36.3, 4.6; IR (ATR) ν: 95, 85, 948 cm - ; RMS (APPI) m/z calcd for C 6 7 F 3 [M] , found 66.69; [α] 4 D = (c =., CCl 3, 97% ee); PLC conditions: Chiralcel OD-, hexane (%), f:.5 ml/min, tr: 9., 9.8 min (97% ee). (R)--(3-cyclohexylpropa-,-dien--yl)-3-methoxybenzene ((R)-3i) OMe Cy Colorless oil. NMR (CDCl 3, 4 Mz) δ: (m, 5), (m, ), (m, ), (m, ),.9-.7 (m, ), 3.8 (s, 3), 5.65 (dd,, J = 6.4, 6.4 z), 6. (dd,, J = 6.4,.8 z), 6.73 (dd,, J = 8.,.4 z), (m, ), 7. (dd,, J = 8. z); 3 C NMR (CDCl 3, Mz) δ: 6., 6., 6., 33.5, 33.5, 37.5, 55., 95.3,.,.6,.3, 9., 9.4, 36.7, 59.8, 4.; IR (ATR) ν: 9, 849, 946 cm - ; RMS (APPI) m/z calcd for 3

4 C 6 O [M] , found 8.53; [α] D 4 = (c =.97, CCl 3, 94% ee); PLC conditions: Chiralcel OJ-, hexane/i-pro = 99:, f:.5 ml/min, tr:.5,.4 min (94% ee) (R)--(3-cyclohexylpropa-,-dien--yl)naphthalene ((R)-3j) Colorless solid. NMR (CDCl 3, 4 Mz) δ: (m, 5), (m, ), Cy (m, ), (m, ),.3-. (m, ), 5.64 (dd,, J = 6.4 z), 6.34 (dd,, J = 6.4, 4.8 z), (m, ), 7.5 (dd,, J = 8.8,. z), 7.64 (s, ), (m, 3); 3 C NMR (CDCl 3, Mz) δ: 6., 6., 33., 33., 37.6, 95.8,.3, 4.5, 5., 5.4, 6., 7.6, 7.7, 8., 3.5, 3.7, 33.7, 4.7; IR (ATR) ν: 9, 849, 946 cm - ; RMS (APPI) m/z calcd for C 9 [M] , found ; mp C; [α] 6 D = (c =.3, CCl 3, 96% ee) ; PLC conditions: Chiralcel AS-, hexane (%), f:.5 ml/min, tr: 9.9,. min, (96% ee). (R)-deca-,-dien--ylbenzene ((R)-3k) [α] 4 D = (c =.8, CCl 3, 97% ee); PLC conditions: Chiralcel OD-, hexane (%), n-ep f:.5 ml/min, tr:.,.7 min (97% ee). (R)--(deca-,-dien--yl)-4-(trifluoromethyl)benzene ((R)-3l) CF 3 n-ep Colorless oil. NMR (CDCl 3, 6 Mz) δ:.87 (t, 3, J = 7. z), (m, 8), (m, ),.4 (ddt,, J = 7., 7., 3. z), 5.63 (dt,, J = 7., 7. z), 6.4 (dt,, J = 7., 3. z), 7.37 (d,, J = 7.8 z), 7.53 (d,, J = 7.8 z); 3 C NMR (CDCl 3, Mz) δ: 4.,.6, 8.5, 9.9, 9.9, 9.4, 3.9, 93.8, 95.7, 4.3 (q, J = 7 z), 5.4 (q, J = 3.8 z), 6.6, 8.5 (q, J = 3 z), 39., 6.; IR (ATR) ν: 95, 855, 949 cm - ; RMS (APPI) m/z calcd for C 7 F 3 [M] , found 8.59; [α] 6 D = -9.6 (c =., CCl 3, 96% ee); PLC conditions: Chiralcel OD-, hexane (%), f:.5 ml/min, tr: 8., 8.6 min (96% ee). (R)-N-(4,4-dimethylpent--yn--yl)-4-methyl-N-(4-phenylbuta-,3-dien--yl)benzenesulfonamide ((R)-6) Ph TsN t-bu Colorless solid. NMR (CDCl 3, 4 Mz) δ:.87 (s, 9),.4 (s, 3), 3.9 (ddd,, J = 4., 7.,. z), 4. (dd,, J = 4., 6.8,.8 z), 4. (s, ), 5.49 (ddd,, J = 7., 6.8, 6.8 z), 6. (ddd, J = 6.8,.8,. z), (m, ), (m, 6), 7.74 (d,, J = 7.6 z); 3 C NMR (CDCl 3, 5 Mz) δ:.4, 7., 3.4, 36.6, 45.5, 7.4, 9.4, 94.9, 96., 6.9, 7.3, 7.7, 8.6, 9.6, 33.5, 36., 43.3, 6.7; IR (ATR) ν: 969, 95, 348, 6 cm - ; RMS (ESI) m/z calcd for C 4 7 NNaO S [M+Na] , found ; mp. 6-6 C; [α] 5 D = -7. (c =.99, CCl 3, 7% ee); PLC conditions: Chiralpak IA, hexane/i-pro = 9:, f:. ml/min, tr: 6., 6.5 min (9% ee). 4

5 C. General Procedure for ydrocyanation A solution of PMePh (4 µl,.75 mmol) and Ni[P(OPh) 3 ] 4 (4.4 mg,.9 mmol) in toluene (9 µl) was heated under Ar atmosphere at C for min. After cooling to room temperature, a solution of allene (.9 mmol) and acetonecyanohydrin (84 µl,.94 mmol) in toluene (8 µl) were added and heated until the allene was disappeared. The reaction mixture was filtrated through Celite, concentrated under vacuo and purified by column chromatography. Spectral data of (R)-3a, (S)-3d-g and 3k were identical to the literature data. (R,E)--(tert-butyl)-4-phenylbut-3-enenitrile ((R)-4a) [α] 5 D = +8.6 (c =.67, CCl 3, 94% ee); PLC conditions: Chiralcel OD-, hexane/i-pro = 99:, f:. ml/min, tr: 9.4,. min (97% ee). (R,E)--(tert-butyl)-4-(4-(trifluoromethyl)phenyl)but-3-enenitrile ((R)-4b) CF 3 Colorless solid. NMR (CDCl 3, 4 Mz) δ:.3 (s, 9), 3. (dd,, J = 7.,. z), 6. (dd,, J = 6., 7. z), 6.76 (d,, J = 6. z), 7.49 (d,, J = 8.4 z), 7.6 (d,, J = 8.4 z); 3 C NMR (CDCl 3, Mz) δ: 7.3, 34.8, 46.7, 9., 3.5, 4. (q, J = 7. z), 5.6, (q, J = 3.8 z), 6.7, 3. (q, J = 33.5 z), 33.7, 39.; IR (ATR) ν: 968, 39 cm - ; RMS (APPI) m/z calcd for C 5 7 NF 3 [M+] , found 68.3; mp. 5-5 C; [α] 5 D = +7. (c =., CCl 3, 94% ee); PLC conditions; Chiralcel OJ-, hexane/i-pro = 99:, f:. ml/min, tr: 5., 8.8 min (94% ee). (R,E)--(tert-butyl)-4-(4-methoxyphenyl)but-3-enenitrile ((R)-4c) OMe Colorless solid. NMR (CDCl 3, 4 Mz) δ:. (s, 9), 3.5 (d,, J = 7. z), 3.8 (s, 3), 5.97 (dd,, J = 5.6, 7. z), 6.63 (d,, J = 6. z), 6.87 (d,, J = 8. z), 7.33 (d,, J = 8. z); 3 C NMR (CDCl 3, Mz) δ: 7.3, 34.6, 46.7, 55.3, 4., 8.4, 9.5, 7.7, 8.6, 34.4, 59.6; IR (ATR) ν: 964, 35 cm - ; RMS (APPI) m/z calcd for C 5 ON [M+] , found 5.539; mp C; [α] 5 D = +.7 (c =., CCl 3, 84% ee); PLC conditions: Chiralpak IA, hexane/i-pro = 98:, f:. ml/min, tr: 9., 9.8 min (84% ee). (S,E)--cyclohexyl-4-phenylbut-3-enenitrile ((S)-4d) [α] D 5 = +9. (c =.9, CCl 3, 97% ee)*; PLC conditions: Chiralcel OD-, hexane/i-pro = 99:, f:. ml/min, tr:.7, 3. min (78% ee). *Measured after recrystallization from hexane. (S,E)--cyclohexyl-4-(4-(trifluoromethyl)phenyl)but-3-enenitrile ((S)-4e) 5 CF 3 [α] D = (c =.43, CCl 3, 8% ee); PLC conditions: Chiralpak IB, hexane/i-pro = 99:, f:. ml/min, tr: 8.4, 8.8 min (8% ee). 5

6 (S,E)--cyclohexyl-4-(4-methoxyphenyl)but-3-enenitrile ((S)-4f) OMe [α] 5 D = +.73 (c =., CCl 3, 65% ee); PLC conditions: Chiralpak IB, hexane/i-pro = 98:, f:. ml/min, tr: 8., 8.5 min (65% ee). (S,E)-4-(4-bromophenyl)--cyclohexylbut-3-enenitrile ((S)-4g) Br [α] 5 D = (c =.5, CCl 3 ) Ee was determined after converted to (S)-S (Scheme S). Scheme S. Reduction of (S)-4g Br i) DIBAL- (.5 eq.) toluene (. M), -78 C, h Br (S)-4g ii) NaB 4 (4. eq.) MeO (. M), C to rt, 7 h O (S)-S: % ( steps), 66% ee (S,E)-4-(4-bromophenyl)--cyclohexylbut-3-en--ol ((S)-S) Br O Colorless solid. NMR (CDCl 3, 4 Mz) δ: (m, 6), (m, ), (m, 5),.7-.4 (m, ), 3.57 (dd,, J =., 9. z), (m, ), 6.5 (dd,, J = 6.,. z), 6.4 (d,, J = 6. z), 7.4 (d,, J = 8.4 z), 7.43 (d,, J = 8.4 z) ; 3 C NMR (CDCl 3, Mz) δ: 6.37, 6.4, 6.5, 3.4, 3., 38.9, 5., 63.8,.9, 7.6, 3., 3.6, 3.8, 36.; IR (ATR) ν: 389, 9, 849 cm - ; RMS (APPI) m/z calcd for C 6 OBr [M+] , found 39.86; mp C; [α] 3 D = +8.8 (c =.7, CCl 3, 66% ee); PLC conditions: Chiralcel OJ-, hexane/i-pro = 95:5, f:. ml/min, tr: 9.4,.6 min (66% ee). (S,E)--cyclohexyl-4-(3-(trifluoromethyl)phenyl)but-3-enenitrile ((S)-4h) CF 3 Colorless oil. NMR (CDCl 3, 4 Mz) δ:.3-.9 (m, 5), (m, 6), 3.33 (dd,, J = 6.4, 6.4 z), 6. (dd,, J = 6., 6.4 z), 6.74 (d,, J = 6. z), 7.45 (dd,, J = 7.6, 7.6 z), (m,,), 7.6 (s, ); 3 C NMR (CDCl 3, Mz) δ: 5.77, 5.79, 5.9, 9.6, 3., 4.8, 4., 8., 3. (q, J =.9 z), 4. (q, J = 7. z), 4., 4.7 (q, J =.7 z), 9., 9.8, 3. (q, 3.6 z), 3.5, 36.5; IR (ATR) ν: 98, 855, 4 cm - ; RMS (APPI) m/z calcd for C 7 8 F 3 N [M] , found ; [α] 5 D = (c =.94, CCl 3, 8% ee); PLC conditions: Chiralpak IB, hexane/i-pro = 99:, f:. ml/min, tr: 9.,. min (8% ee). (S,E)--cyclohexyl-4-(3-methoxyphenyl)but-3-enenitrile ((S)-4i) OMe Colorless oil. NMR (CDCl 3, 4 Mz) δ:.3-.9 (m, 5), (m, ), (m, 4), 3.3 (dd,, J = 6.4, 6.4 z), 3.8 (s, 3), 6.3 (dd,, J = 6., 6.4 z), 6.67 (d,, J = 6. z), 6.83 (d,, J = 8. z), 6.9 (s, ), 6.97 (d,, J = 8. 6

7 z), 7.5 (dd,, J = 8., 8. z); 3 C NMR (CDCl 3, Mz) δ: 5.8, 5.8, 5.9, 9.6, 3.9, 4.8, 4., 55.,.9, 3.7, 9., 9.3,.4, 9.6, 33.8, 37., 59.8; IR (ATR) ν: 96, 853, 39 cm - ; RMS (APPI) m/z calcd for C 7 NO [M] , found 55.6; [α] 5 D = +6.4 (c =.79, CCl 3, 74% ee); PLC conditions: Chiralpak IB, hexane/i-pro = 98:, f:. ml/min, tr: 9.3, 5.9 min (74% ee). (S,E)--cyclohexyl-4-(naphthalen--yl)but-3-enenitrile ((S)-4j) Colorless solid. NMR (CDCl 3, 4 Mz) δ:.8-.3 (m, 5), (m, 6), 3.36 (ddd,, J = 6.8,.4 z), 6.7 (dd,, J = 6., 6.8 z), 6.86 (d,, J = 6 z), (m, ), 7.57 (d,, J = 8.8 z), 7.79 (s, ), (m, 3); 3 C NMR (CDCl 3, 5 Mz) δ: 5.8, 5.8, 6., 9.6, 3., 4.9, 4., 9.4,.4, 3.3, 6., 6.4, 6.8, 7.7, 8., 8.4, 33.6, 33., 33.5, 34.; IR (ATR) ν: 97, 853, 37 cm - ; RMS (APPI) m/z calcd for C N [M+] , found 76.74; mp. 3-4 C; [α] 5 D = +6.7 (c =.9, CCl 3 ). Ee was determined after converted to the corresponding alcohol (S)-S (Scheme S). Scheme S. Reduction of (S)-4j i) DIBAL- (.5 eq.) toluene (. M), -78 C, h (S)-4j ii) NaB 4 (8. eq.) MeO (. M), C to rt, h O (S)-S: 4% ( steps), 7% ee (S,E)--cyclohexyl-4-(naphthalen--yl)but-3-en--ol ((S)-S) Colorless solid. NMR (CDCl 3, 4 Mz) δ:.4-.9 (m, 5), (m, ), (m, 5),.4-.3 (m, ), 3.6 (dd,, J =.4, 8.4 z), (m, ), O 6.8 (dd,, J = 5.6,. z), 6.63 (d,, J = 5.6 z), (m, ), 7.6 (dd,, J = 8.,. z), 7.7 (s, ), (m, 3); 3 C NMR (CDCl 3, Mz) δ: 6.4, 6.4, 6.5, 3.5, 3.3, 39., 5.5, 64.9, 3.5, 5.7, 5.8, 6., 7.6, 7.9, 8., 3.7, 3.8, 33.3, 33.6, 34.5; IR (ATR) ν: 34, 9, 849 cm - ; RMS (APPI) m/z calcd for C 4 N [M] + 8.8, found 8.87; mp C; [α] 3 D = +8.8 (c =.7, CCl 3, 7% ee); PLC Conditions: Chiralcel IA, hexane/i-pro = 95:5, f:. ml/min, tr:.5, 5.9 min (7% ee). (S,E)--styryloctanenitrile ((S)-4k) [α] 5 D = +8. (c =.4, CCl 3, 47% ee); PLC cconditions: Chiralpak IB, hexane/i-pro = 99:, f:. ml/min, tr: 9.5, 9.7 min (47% ee). (S,E)--(4-(trifluoromethyl)styryl)nonanenitrile ((S)-4l) CF 3 Colorless oil. NMR (CDCl 3, 4 Mz) δ:.89 (t, 3, J = 7. z), (m, 9), (m, ),.79 (dt,, J = 7., 7. z), 3.46 (dt,, J = 6.4, 6.4 z), 6.4 (dd, 7

8 , J = 6., 6.4 z), 6.78 (d,, J = 6. z), 7.48 (d,, 8. z), 7.59 (d,, J = 8. z); 3 C NMR (CDCl 3, Mz) δ: 4.,.5, 6.8, 8.9, 8.93, 3.6, 33., 34.4, 99.8, 4. (q, J = 7.), 5.6 (q, J = 3.8 z), 6., 6.7, 3. (q, J = 3.6 z), 3.8, 39.; IR (ATR) ν: 98, 858, 4 cm - ; RMS (APPI) m/z calcd for C 8 F 3 N [M] , found ; [α] 5 D = +6.8 (c =.5, CCl 3, 63% ee); PLC conditions*: Chiralcel AD-, hexane/i-pro = 99:, f:. ml/min, tr:.3,.3 min (63% ee). *Racemic sample was separated by using Chiralcpak IA better than Chiralcel AD-, however chiral sample could not be separated very well by using Chiralcpak IA. Both charts are shown in page xx. (E)-3,3-dimethyl--((S)-4-((E)-styryl)--tosylpyrrolidin-3-ylidene)butanenitrile ((S)-7) Ph TsN t-bu Colorless solid. NMR (CDCl 3, 6 Mz) δ:. (s, 9),.45 (s, 3), 3.6 (dd,, J =.4, 6. z), 3.5 (d,, J = 9.6 z), 3.78 (dd,, 7.8, 6. z), 3.96 (d,, J = 6. z), 4.33 (d,, J = 6. z), 5.99 (dd,, J = 6., 7.8 z), 6.57 (d,, J = 6. z), (m, ), (m, 4), 7.37 (d,, J = 7.8 z), 7.73 (d,, J = 7.8 z); 3 C NMR (CDCl 3, Mz) δ:.6, 9.6, 35.4, 49.5, 5., 5.8, 7.,., 5.9, 6.6, 7.8, 8.5, 9.9, 3., 3., 3.4, 36.3, 44.3, 53.3; IR (ATR) ν: 968,, 348, 6 cm - ; RMS (ESI) m/z calcd for C 5 8 N NaO S [M+Na] , found ; mp. 3-4 C; [α] 5 D = (c =.5, CCl 3, 4% ee); PLC conditions: Chiralpak IB, hexane/i-pro = 75:5, f:. ml/min, tr: 6.6, 8. min (64% ee). D. Determination of absolute stereochemistry of (R)-4a and (S)-4d Absolute stereochemistry of (R)-4a was determined after conversion to (R)-S3 and comparing specific optical rotation with that of reported (S)-S3 4 (Scheme S3). Scheme S3. Reduction of (R)-4a i) Pd/C,, AcOEt, rt ii) DIBAL- (.5 eq.) toluene (. M), -78 C,.5 h (R)-4a (98% ee) iii) NaB 4 (8. eq.) MeO (. M), C to rt, h O (R)-S3 (36%, 3 steps) [a] D +8.3 (c =.83, CCl 3 ) O (S)-S3 (84% ee) [α] D -.6 (c =.7, CCl 3 ) Absolute stereochemistry of (S)-4d was determined after conversion to (S)-S4 and comparing specific optical rotation with that of reported (R)-S4 5 (Scheme S4). Scheme S4. Reduction of (S)-4d i) DIBAL- (.5 eq.) toluene (. M), -78 C,.5 h (S)-4d (6% ee) ii) NaB 4 (8. eq.) MeO (. M), C to rt, h O (R)-S4 (4%, steps) [α] D (c =.43, C Cl ) O (S)-S (96% ee) [α] D (c =.5, C Cl ) 8

9 E. Examination of time course A solution of phosphorous ligand and Ni[P(OPh) 3 ] 4 (33.7 mg,.8 mmol) in toluene (85 µl) was heated under Ar atmosphere at C for min. After cooling to room temperature, a solution of allene (.8 mmol), acetonecyanohydrin (5 µl,.56 mmol) and 4-methoxybiphenyl (.4 mg,.56 mmol) as an internal standard in toluene (4 µl) were added and heated. The sample was taken from the reaction mixture via syringe in a specific time, filtrated through Celite and concentrated under vacuo. The yield was calculated according to the NMR spectra and the ee was determined by PLC after purification by preparative TLC. Table S. Time course profiling time (min) (R)-3a y. (%) (ee %) (R)-4a y. (%) (ee %) (R)-3d y. (%) (ee %) (S)-4d y. (%) (ee %) (R)-3k y. (%) (ee %) (S)-4k y. (%) (ee %) (99) - 55 (96) 4 (9) (9) 4 (8) (-) (-) - 8 (98) 44 (98) 59 (98) 84 (97) 9 (97) (96) 9 (94) 69 (9) 37 (8) 9 (8) (-) - (-) (78) 8 (78) 47 (74) 67 (74) 76 (7) - (97) 7 (9) (-) (-) 5 (5) 74 (48) F. Examination of racemization A solution of phosphorous ligand and Ni[P(OPh) 3 ] 4 (. mg,.94 mmol) in toluene ( µl) was heated under Ar atmosphere at C for min. After cooling to room temperature, a solution of (R)-3e (5. mg,.94 mmol) in toluene (35 µl) were added and heated for 6 h. The reaction mixture was filtrated through Celite, concentrated under vacuo and purified by column chromatography to provide 3e (6. mg,.3 mmol, 4%, % ee) and 8 (3.8 mg,.4 mmol, 5%). (E)--(3-cyclohexylideneprop--en--yl)-4-(trifluoromethyl)benzene (8) Colorless solid. NMR (CDCl 3, 4 Mz) δ:.6 (bs, 6),. (bs, ),.4 (bs, CF 3 ), 5.97 (d,, J =.8 z), 6.46 (d,, J = 5.6 z), 7.4 (dd,, J = 5.6,.8 z), 7.46 (d,, J = 8.4 z), 7.53 (d,, J = 8.4 z); 3 C NMR (CDCl 3, 5 Mz) δ: 6.7, 7.9, 8.6, 9.7, 37.6,., 3.3 (J = 7 z), 5.5 (J = 4. z), 6., 7.3, 8., 8.5 (J = 3.3 z), 4.7, 47.; IR (ATR) ν: 97, 85, 638, 68, 3 cm - ; RMS (APPI) m/z calcd for C 6 7 F 3 [M] , found 66.77; mp C. G. References ) Lu, R., Ye, J. Cao, T., Chen, B., Fan, W. Lin, W., Liu, J., Luo,., Miao, B., Ni, S., Tang, X., Wang, N., Wang, Y., Xie, X., Yu, Q., Yuan, W., Zhang, W., Zhu, C., Ma, S. Org. Lett. 3, 5, ) Arai, S., ori,., Amako, Y., Nishida, A. 5, Chem. Commun. 5, ) Elsevier, C. J., Vermeer, P. J. Org. Chem. 989, 54,

10 4) Spino, C., Gund, V. G., Nadeau, S. J. Comb. Chem. 5, 7, ) Kim,., MacMillan, D. W. C. J. Am. Chem. Soc. 8, 3,

11 . PLC Charts (R)-(4,4-dimethylpenta-,-dien--yl)benzene ((R)-3a) t-bu Administrator_7 3 - C Administrator_79 - C (R)--(4,4-dimethylpenta-,-dien--yl)-4-(trifluoromethyl)benzene ((R)-3b) CF 3 t-bu

12 (R)--(4,4-dimethylpenta-,-dien--yl)-4-methoxybenzene ((R)-3c) OMe t-bu (R)-(3-cyclohexylpropa-,-dien--yl)benzene ((R)-3d) Cy Administrator_9 3 - C 6 Administrator_8 - C # tr % # tr %

13 (R)--(3-cyclohexylpropa-,-dien--yl)-4-(trifluoromethyl)benzene ((R)-3e) CF 3 Cy (R)--(3-cyclohexylpropa-,-dien--yl)-4-methoxybenzene ((R)-3f) OMe Cy

14 (R)--bromo-4-(3-cyclohexylpropa-,-dien--yl)benzene ((R)-3g) Br Cy (R)--(3-cyclohexylpropa-,-dien--yl)-3-(trifluoromethyl)benzene ((R)-3h) Cy CF

15 (R)--(3-cyclohexylpropa-,-dien--yl)-3-methoxybenzene ((R)-3i) Cy OMe (R)--(3-cyclohexylpropa-,-dien--yl)naphthalene ((R)-3j) Cy # tr % # tr %

16 (R)-deca-,-dien--ylbenzene ((R)-3k) n-ep (R)--(deca-,-dien--yl)-4-(trifluoromethyl)benzene ((R)-3l) CF 3 n-ep

17 (R)-N-(4,4-dimethylpent--yn--yl)-4-methyl-N-(4-phenylbuta-,3-dien--yl)benzenesulfonamide ((R)-6) Ph TsN t-bu Administrator_8 7 - C Administrator_5 - C (R,E)--(tert-butyl)-4-phenylbut-3-enenitrile ((R)-4a) Administrator_7 4 - C Administrator_ C

18 (R,E)--(tert-butyl)-4-(4-(trifluoromethyl)phenyl)but-3-enenitrile ((R)-4b) CF # tr % # tr % (R,E)--(tert-butyl)-4-(4-methoxyphenyl)but-3-enenitrile ((R)-4c) OMe 6 Administrator_ C 4 Administrator_94 - C

19 (S,E)--cyclohexyl-4-phenylbut-3-enenitrile ((S)-4d) Administrator_7 - C Administrator_5 - C (S,E)--cyclohexyl-4-(4-(trifluoromethyl)phenyl)but-3-enenitrile ((R)-4e) CF

20 (S,E)--cyclohexyl-4-(4-methoxyphenyl)but-3-enenitrile ((S)-4f) OMe (S,E)-4-(4-bromophenyl)--cyclohexylbut-3-en--ol ((S)-S) Br O Administrator_7 4 - C Administrator_47 - C

21 (S,E)--cyclohexyl-4-(3-(trifluoromethyl)phenyl)but-3-enenitrile ((S)-4h) CF (S,E)--cyclohexyl-4-(3-methoxyphenyl)but-3-enenitrile ((S)-4i) OMe Administrator_4 - C

22 (S,E)--cyclohexyl-4-(naphthalen--yl)but-3-en--ol ((S)-S) O Administrator_34 - C Administrator_6 - C (S,E)--styryloctanenitrile ((S)-4k) 4 Administrator_7 7 - C 5 Administrator_ C

23 (S,E)--(4-(trifluoromethyl)styryl)nonanenitrile ((S)-4l) CF 3 Chiralcel AD- Administrator_7 - C Chiralpak IA Administrator_ C Administrator_7 5 - C

24 (E)-3,3-dimethyl--((S)-4-((E)-styryl)--tosylpyrrolidin-3-ylidene)butanenitrile ((S)-7) Ph TsN t-bu Administrator_95 - C Administrator_7 5 - C

25 CF 3 t-bu (R)-3b

26 OMe t-bu (R)-3c

27 Cy CF 3 (R)-3h

28 Cy OMe (R)-3i

29 Cy (R)-3j

30 CF 3 n-ep (R)-3k

31 CF 3 t-bu (R)-4b

32 OMe t-bu (R)-4c

33 Cy (S)-4h CF 3

34 Cy (S)-4i OMe

35 Cy (S)-4j

36 CF 3 n-ep (S)-4k

37 Ph TsN (R)-6 t-bu

38 TsN Ph (S)-7 t-bu

39 8 CF 3

40 Br Cy O (S)-S

41 Cy O (S)-S