Chiral P,Olefin Ligands with Rotamers for Palladium-Catalyzed Asymmetric Allylic Substitution Reactions

Abstract

We synthesized a series of phosphine–olefin-type chiral aminophosphines, and we confirmed that these each exists as two rotamers at the C(aryl)–N(amine) bond. We also investigated the ability of these aminophosphines to act as chiral ligands for Pd-catalyzed asymmetric allylic substitution reactions, such as the alkylation of allylic acetates with malonates or indoles, and we found they gave high enantio­selectivities (up to 98% ee).

Key words

phosphines - ligands - rotamers - asymmetric catalysis - palladium catalysis - allylic acetates

• References and Notes


For selected reviews, see:
• 1a Liu Y, Han S.-J, Liu W.-B, Stoltz BM. Acc. Chem. Res. 2015; 48: 740
• 1b Trost BM. Tetrahedron 2015; 71: 5708
• 1c Trost BM. Org. Process Res. Dev. 2012; 16: 185
• 1d Guerrero Rios I, Rosas-Hernandez A, Martin E. Molecules 2011; 16: 970
• 1e Diéguez M, Pàmies O. Acc. Chem. Res. 2010; 43: 312
• 1f Mohr JT, Stoltz BM. Chem. Asian J. 2007; 2: 1476
• 1g Guiry PJ, Saunders CP. Adv. Synth. Catal. 2004; 346: 497
• 1h Trost BM. J. Org. Chem. 2004; 69: 5813
• 1i Trost BM, Crawley ML. Chem. Rev. 2003; 103: 2921
• 1j Graening T, Schmalz H.-G. Angew. Chem. Int. Ed. 2003; 42: 2580
• 1k Trost BM, Van Vranken DL. Chem. Rev. 1996; 96: 395
• 2 For a review, see: Feng X, Du H. Chin. J. Org. Chem. 2015; 35: 259
• 3a Kamikawa K, Tseng Y.-Y, Jian J.-H, Takahashi T, Ogasawara M. J. Am. Chem. Soc. 2017; 139: 1545
• 3b Gandi VR, Lu Y, Hayashi T. Tetrahedron: Asymmetry 2015; 26: 679
• 3c Liu Y, Feng X, Du H. Org. Biomol. Chem. 2015; 13: 125
• 3d Ogasawara M, Tseng Y.-Y, Arae S, Morita T, Nakaya T, Wu W.-Y, Takahashi T, Kamikawa K. J. Am. Chem. Soc. 2014; 136: 9377
• 3e Wang H.-L, Hu R.-B, Zhang H, Zhou A.-X, Yang S.-D. Org. Lett. 2013; 15: 5302
• 3f Liu Z, Du H. Org. Lett. 2013; 15: 740
• 3g Liu Y, Cao Z, Du H. J. Org. Chem. 2012; 77: 4479
• 3h Cao Z, Liu Z, Liu Y, Du H. J. Org. Chem. 2011; 76: 6401
• 3i Shintani R, Narui R, Tsutsumi Y, Hayashi S, Hayashi T. Chem. Commun. 2011; 47: 6123
• 3j Liu Z, Cao Z, Du H. Org. Biomol. Chem. 2011; 9: 5369
• 3k Cao Z, Liu Y, Liu Z, Feng X, Zhuang M, Du H. Org. Lett. 2011; 13: 2164
• 3l Liu Z, Du H. Org. Lett. 2010; 12: 3054
• 3m Stemmler RT, Bolm C. Synlett 2007; 1365
• 3n Duan W.-L, Iwamura H, Shintani R, Hayashi T. J. Am. Chem. Soc. 2007; 129: 2130
• 3o Kasák P, Arion VB, Widhalm MA. Tetrahedron: Asymmetry 2006; 17: 3084
• 3p Shintani R, Duan W.-L, Okamoto K, Hayashi T. Tetrahedron: Asymmetry 2005; 16: 3400
• 3q Shintani R, Duan W.-L, Nagano T, Okada A, Hayashi T. Angew. Chem. Int. Ed. 2005; 44: 4611
• 3r Marie P, Deblon S, Breher F, Geier J, Böhler C, Rüegger H, Schönberg H, Grützmacher H. Chem. Eur. J. 2004; 10: 4198
• 4a Mino T, Youda J, Ebisawa T, Shima Y, Nishikawa K, Yoshida Y, Sakamoto M. J. Oleo Sci. 2018; 67: 1189
• 4b Mino T, Nishikawa K, Asano M, Shima Y, Ebisawa T, Yoshida Y, Sakamoto M. Org. Biomol. Chem. 2016; 14: 7509
• 5 Mino T, Yamaguchi D, Masuda C, Youda J, Ebisawa T, Yoshida Y, Sakamoto M. Org. Biomol. Chem. 2019; 17: 1455
• 6 Hattori T, Komuro Y, Hayashizaka N, Takahashi H, Miyano S. Enantiomer 1997; 2: 203
• 7 Mino T, Tanaka Y, Sakamoto M, Fujita T. Tetrahedron: Asymmetry 2001; 12: 2435
• 8a Mino T, Tanaka Y, Sakamoto M, Fujita T. Heterocycles 2000; 53: 1485
• 8b Hattori T, Sakamoto J, Hayashizaka N, Miyano S. Synthesis 1994; 199
• 9 [2-(Diphenylphosphoryl)-6-methoxyphenyl][(1S)-1-phenylethyl]amine [(S)-8a] A 1.6 M solution of BuLi in hexane (9.4 mL, 15.0 mmol) was slowly added to a solution of [(1S)-1-phenylethyl]amine (1.82 g, 15.0 mmol) in THF (35 mL) at –80 °C. Phosphine oxide 7a (1.69 g, 5.0 mmol) was added at r.t., and the mixture was stirred for 21 h at r.t. The mixture was then diluted with Et₂O, and the reaction was quenched with sat. aq NH₄Cl. The organic layer was washed with brine, dried (MgSO₄), and concentrated under reduced pressure. The residue was purified by chromatography [silica gel, hexane–EtOAc (2:1)] to give a beige solid; yield: 1.60 g (75%, 3.74 mmol); mp 124–126 °C; [α]_D ²⁰ +99.1 (c 0.50, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.68–7.53 (m, 6 H), 7.50–7.41 (m, 4 H), 7.36 (br s, 1 H), 7.15–7.12 (m, 2 H), 7.06–7.03 (m, 3 H), 6.79 (d, J = 7.1 Hz, 1 H), 6.56 (dt, J = 3.6 and 7.8 Hz, 1 H), 6.42 (ddd, J = 1.4, 7.7, 14.0 Hz, 1 H), 5.10 (t, J = 6.1 Hz, 1 H), 3.69 (s, 3 H), 1.33 (d, J = 6.8 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 150.7 (d, J_CP = 11.6 Hz), 146.4, 144.1 (d, J_CP = 5.5 Hz), 133.0 (d, J_CP = 103.9 Hz), 132.6 (d, J_CP = 104.5 Hz), 132.2 (d, J_CP = 10.1 Hz) (2 C), 132.0 (d, J_CP = 9.9 Hz) (2 C), 131.8 (d, J_CP = 2.5 Hz), 131.7 (d, J_CP = 2.5 Hz), 128.4 (d, J_CP = 12.2 Hz) (4 C), 127.9 (2 C), 126.2 (2 C), 126.0, 125.6 (d, J_CP = 11.0 Hz), 117.5 (d, J_CP = 15.5), 115.6 (d, J_CP = 2.5 Hz), 115.5 (d, J_CP = 104.2 Hz), 55.5, 55.4, 24.6. ³¹P NMR (121 MHz, CDCl₃): δ = 37.5. EI-MS: m/z (%): 427 (M⁺, 30), 412 (100). HRMS (ESI-Orbitrap): m/z [M + H]⁺ calcd for C₂₇H₂₇NO₂P: 428.1774; found: 428.1766. [2-(Diphenylphosphoryl)-6-methoxyphenyl][(1S)-1-phenylethyl][(2E)-3-phenylprop-2-en-1-yl]amine [(S)-9a] To the solution of the phosphine oxide (S)-8a (2.14 g, 5.0 mmol) in MeCN (50 mL) at r.t. were added K₂CO₃ (3.46 g, 25 mmol) and cinnamyl bromide (1.18 g, 6.0 mmol) in MeCN (20 mL), and the mixture was stirred at 60 °C for 22 h. The mixture was then filtered and concentrated under reduced pressure. The residue was purified by chromatography [silica gel, hexane–EtOAc (5:1)] to give a white solid; yield: 2.29 g (84%, 4.22 mmol); mp 169–171 °C; [α]_D ²⁰ +53.1 (c 0.36, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.84–7.73 (m, 4 H), 7.47–7.38 (m, 8 H), 7.24–7.01 (m, 10 H), 6.66 (ddd, J = 1.2, 7.7, 13.9 Hz, 1 H), 5.83 (d, J = 15.9 Hz, 1 H), 5.33 (ddd, J = 7.0, 7.0, 15.9 Hz, 1 H), 4.67 (q, J = 6.0 Hz, 1 H), 3.73 (dd, J = 7.5, 7.6 Hz, 1 H), 3.67 (s, 3 H), 3.26 (dd, J = 6.5, 15.1 Hz, 1 H), 1.11 (d, J = 6.7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 160.1 (d, J_CP = 11.5 Hz), 145.3, 143.8 (d, J_CP = 4.4 Hz), 137.8, 134.7 (d, J_CP = 106.6 Hz), 134.0 (d, J_CP = 105.3 Hz), 133.0 (d, J_CP = 103.8 Hz), 132.1 (d, J_CP = 9.0 Hz) (2 C), 131.1(931) (d, J_CP = 2.6 Hz), 131.1(925) (d, J_CP = 9.4 Hz) (2 C), 131.0 (d, J_CP = 2.8 Hz), 129.5, 128.9, 128.5 (2 C), 128.2 (d, J_CP = 12.2 Hz) (2 C), 128.1 (d, J_CP = 11.7 Hz) (2 C), 128.0 (2 C), 127.6 (2 C), 126.7 (d, J_CP = 12.4 Hz), 126.4, 126.3, 126.2 (d, J_CP = 3.3 Hz), 126.0 (2 C), 115.6 (d, J_CP = 2.3 Hz), 62.3, 56.9, 55.1, 22.4. ³¹P NMR (121 MHz, CDCl₃): δ = 27.5. EI-MS: m/z (%) = 543 (M⁺, 0.15), 438 (100). HRMS (ESI-Orbitrap): m/z [M + H]⁺ calcd for C₃₆H₃₅NO₂P: 544.2400; found: 544.2388. X-ray diffraction analysis: Colorless plate crystals (0.20 × 0.10 × 0.020 mm³) from hexane–CHCl₃; monoclinic space group P21, a = 12.4152(3) Å, b = 8.9538(2) Å, c = 13.5274(3) Å, β = 103.4670(10)°, V = 1462.40(6) ų, Z = 2, ρ = 1.235 g/cm³, μ (Cu Kα) = 1.54178 mm^–1. The structure was solved by the direct method of full-matrix least–squares, where the final R and R_w were 0.0327, 0.0875, respectively, for 4982 reflections. [2-(Diphenylphosphino)-6-methoxyphenyl][(1S)-1-phenylethyl][(2E)-3-phenylprop-2-en-1-yl]amine [(S)-6a] To a mixture of phosphine oxide (S)-9a (1.09 g, 2.0 mmol) and Et₃N (3.1 mL, 22 mmol) in m-xylene (10 mL) was added HSiCl₃ (2.0 mL, 20 mmol) at 0 °C under Ar. The mixture was stirred at 120 °C for 24 h then cooled to r.t. and diluted with Et₂O. The reaction was quenched with 2 M aq NaOH, and the organic layer was washed with brine, dried (MgSO₄), and concentrated under reduced pressure. The residue was purified by chromatography [silica gel, hexane–EtOAc (50:1)]. to give a white solid; yield 0.530 g (50%. 1.0 mmol); mp 55–56 °C; [α]_D ²⁰ +59.6 (c 0.51, CHCl₃); rotamer ratio = 20:1. ¹H NMR (300 MHz, CDCl₃): δ (major rotamer) = 7.66 (d, J = 8.0 Hz, 2 H), 7.37–7.04 (m, 19 H), 6.86 (dd, J = 1.0, 8.1 Hz, 1 H), 6.53 (ddd, J = 1.3, 2.8, 7.6 Hz, 1 H), 6.04–5.94 (m, 1 H), 5.85 (d, J = 15.9 Hz, 1 H), 4.59 (q, J = 6.5 Hz, 1 H), 3.83 (s, 3 H), 3.58–3.42 (m, 2 H), 0.89 (d, J = 6.7 Hz, 3 H); δ (minor rotamer) = 7.66 (d, J = 7.4 Hz, 2 H), 7.37–7.04 (m, 19 H), 6.64 (dd, J = 1.0, 8.1 Hz, 1 H), 6.42–6.39 (m, 1 H), 6.09 (d, J = 16.1 Hz, 1 H), 5.76–5.68 (m, 1 H), 4.81 (q, J = 6.5 Hz, 1 H), 3.75 (s, 3 H), 3.58–3.42 (m, 2 H), 1.50 (d, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.3 (d, J_CP = 3.9 Hz), 147.1, 141.9 (d, J_CP = 4.2 Hz), 141.1 (d, J_CP = 22.0 Hz), 138.7 (d, J_CP = 14.4 Hz), 138.5 (d, J_CP = 15.1 Hz), 137.6, 134.2 (d, J_CP = 20.5 Hz) (2 C), 134.0 (d, J_CP = 20.5 Hz) (2 C), 130.1, 129.0, 128.2(8) (d, J_CP = 2.0 Hz) (2 C), 128.2(6), 128.2(2) (d, J_CP = 1.0 Hz) (2 C), 128.1(4) (2 C), 128.0(9) (d, J_CP = 1.0 Hz) (2 C), 128.0(3), 128.0(1) (2 C), 126.9, 126.6, 126.4 (2 C), 126.1 (2 C), 111.9, 61.6, 56.3, 55.1, 23.5. ³¹P NMR (121 MHz, CDCl₃): δ (major rotamer) = −16.0; δ (minor rotamer) = −14.1. EI-MS: m/z (%) = 527 (M⁺, 8.2), 422 (100). HRMS (ESI-Orbitrap): m/z [M + H]⁺ calcd for C₃₆H₃₅NOP: 528.2451; found: 528.2441.

For recent examples, see:
• 10a Li S, Zhang J, Li H, Feng L, Peng Jiao P. J. Org. Chem. 2019; 84: 9460
• 10b Imrich MR, Maichle-Mössmer C, Ziegler T. Eur. J. Org. Chem. 2019; 3955
• 10c Hu Y.-L, Wang Z, Yang H, Chen J, Wu Z.-B, Lei Y, Zhou L. Chem. Sci. 2019; 10: 6777
• 10d Baumann T, Brückner R. Angew. Chem. Int. Ed. 2019; 58: 4714
• 10e Qiu Z, Sun R, Teng D. Org. Biomol. Chem. 2018; 16: 7717
• 10f Borràs C, Elias-Rodriguez P, Carmona AT, Robina I, Pàmies O, Diéguez M. Organometallics 2018; 37: 1682
• 10g Argüelles AJ, Sun S, Budaitis BG, Nagorny P. Angew. Chem. Int. Ed. 2018; 57: 5325
• 10h Biosca M, Margalef J, Caldentey X, Besora M, Rodriguez-Escrich C, Saltó J, Cambeiro XC, Maseras F, Pàmies O, Diéguez M, Pericàs MA. ACS Catal. 2018; 8: 3587
• 10i Chang S, Wang L, Lin X. Org. Biomol. Chem. 2018; 16: 2239
• 10j Naganawa Y, Abe H, Nishiyama H. Chem. Commun. 2018; 54: 2674
• 10k Szulc I, Kołodziuk R, Zawisza A. Tetrahedron 2018; 74: 1476
• 10l Yao L, Nie H, Zhang D, Wang L, Zhang Y, Chen W, Li Z, Liu X, Zhang S. ChemCatChem 2018; 10: 804
• 10m Sartorius F, Trebing M, Brückner C, Brückner R. Chem. Eur. J. 2017; 23: 17463
• 10n Ogasawara M, Tseng Y.-Y, Uryu M, Ohya N, Chang N, Ishimoto H, Arae S, Takahashi T, Kamikawa K. Organometallics 2017; 36: 4061
• 11 Palladium-Catalyzed Allylic Alkylation of Malonates; General Procedure BSA (0.15 mL, 0.60 mmol) and the appropriate allylic ester (0.20 mmol) were added to a mixture of [Pd(C₃H₅)Cl]₂ (1.48 mg, 4 μmol), (S)-6d (4.64 mg, 8 μmol), and NaOAc (1.64 mg, 20 μmol) in PhCF₃ (0.4 mL) at r.t. under Ar, and the mixture was stirred for 10 min. A dialkyl malonate (0.60 mmol) was added, and stirring was continued for 24 h at r.t. The mixture was then diluted with Et₂O and water. The organic layer was washed with brine then dried (MgSO₄), filtered, and concentrated in a rotary evaporator. The residue was purified by column chromatography [silica gel, hexane–EtOAc (10:1)]. Dimethyl [(1S,2E)-1,3-Diphenylprop-2-en-1-yl]malonate [(S)-10a]¹⁶ Colorless oil; yield: 55.7 mg (86%, 0.172 mmol, 94% ee); [α]_D ²⁰ –21.6 (c 0.51, CHCl₃). HPLC [Daicel CHIRALPAK AD-H, 0.46 × 25 cm, λ = 254 nm, hexane–i-PrOH (90:10), 0.5 mL/min]: t _R = 26.3 min (minor), 33.3 min (major). ¹H NMR (400 MHz, CDCl₃): δ = 7.34–7.18 (m, 10 H), 6.48 (d, J = 15.8 Hz, 1 H), 6.33 (dd, J = 8.4, 15.7 Hz, 1 H), 4.27 (dd, J = 8.1, 8.6 Hz, 1 H), 3.95 (d, J = 10.8 Hz, 1 H), 3.70 (s, 3 H), 3.52 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 168.2, 167.8, 140.2, 136.8, 131.9, 129.1, 128.7, 128.5, 127.9, 127.6, 127.2, 126.4, 57.7, 52.7, 52.5, 49.2. EI-MS: m/z (%) = 324 (M⁺, 13).

For examples, see:
• 12a Qiu Z, Sun R, Yang K, Teng D. Molecules 2019; 24: 1575
• 12b Zhang L, Xiang S.-H, Wang J, Xiao J, Wang J.-Q, Tan B. Nat. Commun. 2019; 10: 566
• 12c Yamamoto K, Shimizu T, Igawa K, Tomooka K, Hirai G, Suemune H, Usui K. Sci. Rep. 2016; 6: 36211
• 12d Feng B, Pu X.-Y, Liu Z.-C, Xiao W.-J, Chen J.-R. Org. Chem. Front. 2016; 3: 1246
• 12e Xu J.-X, Ye F, Bai X.-F, Zhang J, Xu Z, Zheng Z.-J, Xu L.-W. RSC Adv. 2016; 6: 45495
• 12f Mino T, Ishikawa M, Nishikawa K, Wakui K, Sakamoto M. Tetrahedron: Asymmetry 2013; 24: 499
• 12g Hoshi T, Sasaki K, Sato S, Ishii Y, Suzuki T, Hagiwara H. Org. Lett. 2011; 13: 932
• 12h Cheung HY, Yu W.-Y, Lam FL, Au-Yeung TT.-L, Zhou Z, Chan TH, Chan AS. C. Org. Lett. 2007; 9: 4295
• 13 Palladium-Catalyzed Allylic Alkylation of Indoles; General Procedure PhMe (0.2 mL) was added to a mixture of indole or a substituted indole (0.2 mmol), the appropriate 1,3-diarylprop-2-enyl acetate (60.6 mg, 0.24 mmol), (S)-6a (6.3 mg, 12 μmol), [Pd(C₃H₅)Cl]₂ (2.2 mg, 6 μmol), and KOAc (39.3 mg, 0.4 mol) at r.t. under Ar, and the mixture was stirred for 18 h at 40 °C. The reaction was quenched with H₂O, and the mixture was diluted with Et₂O. The organic layer was washed with H₂O and brine then dried (MgSO₄), filtered, and concentrated in a rotary evaporator. The residue was purified by column chromatography [silica gel, hexane–EtOAc–Et₃N (20:2:1)]. 3-[(1R,2E)-1,3-Diphenylprop-2-en-1-yl]-1H-indole [(R)-11a]⁴ Yellow solid; yield: 48.0 mg (74%, 0.146 mmol, 97% ee); mp 118–120 °C; [α]_D ²⁰ –35.3 (c 0.19, CHCl₃). HPLC [Daicel CHIRALPAKIB, 0.46 × 25 cm, λ = 254 nm, hexane–EtOH (99:1), 0.7 mL/min]: t _R = 56.3 min (major), 63.9 min (minor). ¹H NMR (400 MHz, CDCl₃): δ = 7.98 (br s, 1 H), 7.43–7.15 (m, 13 H), 7.04–7.00 (m, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 6.73 (dd, J = 7.4, 15.8 Hz, 1 H), 6.43 (d, J = 15.9 Hz, 1 H), 5.12 (d, J = 7.3 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 143.3, 137.5, 136.6, 132.5, 130.5, 128.5 (2 C), 128.4, 127.1, 126.8, 126.4, 126.3, 122.6, 122.1, 119.9, 119.4, 118.7, 111.1, 46.2. EI-MS: m/z (%) 309 (M⁺, 100).
• 14 CCDC 1938333 contains the supplementary crystallographic data for compound (S)-9a. The data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

For examples, see:
• 15a Brown JM, Hulmes DI, Guiry PJ. Tetrahedron 1994; 50: 4493
• 15b Sprinz J, Kiefer M, Helmchen G, Reggelin M, Huttner G, Walter O, Zsolnai L. Tetrahedron Lett. 1994; 35: 1523
• 16a Mino T, Asakawa M, Shima Y, Yamada H, Yagishita F, Sakamoto M. Tetrahedron 2015; 71: 5985
• 16b Tanaka Y, Mino T, Akita K, Sakamoto M, Fujita T. J. Org. Chem. 2004; 69: 6679