Highly Enantioselective Pd-Catalyzed Asymmetric Hydrogenation of N-Diphenylphosphinyl Ketimines

Abstract

A variety of substituted N-diphenylphosphinyl imines were hydrogenated using Pd(CF₃CO₂)₂/(S)-SEGPHOS as a catalyst with high enantioselectivities (86.7%-98.6% ee).

palladium - asymmetric synthesis - hydrogenation - N-diphenylphosphinyl imines

References and Notes

1a Comprehensive Asymmetric Catalysis   Jacobsen EN. Pfaltz A. Yamamoto H. Springer; New York: 1999. 

1b Catalytic Asymmetric Synthesis   Ojima I. Wiley-VCH; New York: 2000.  2nd ed: 

2a Tsuji J. Palladium Reagents and Catalysis   John Wiley & Sons; Chichester: 2004. 

2b Negishi E. Handbook of Organopalladium Chemistry for Organic Synthesis   Wiley; Hoboken NJ: 2002. 

2c Heck RF. Pd Reagents in Organic Synthesis   Academic; New York: 1985. 

2d Tietze LF. Ila H. Bell HP. Chem. Rev.  2004,  104:  3453 

3a Noyori R. Angew. Chem. Int. Ed.  2002,  41:  2008 

3b Knowles WS. Angew. Chem. Int. Ed.  2002,  41:  1998 

3c Rossen K. Angew. Chem. Int. Ed.  2001,  40:  4611 

3d Tang W. Zhang X. Chem. Rev.  2003,  103:  3029 

For reviews on the asymmetric hydrogenation of imines, see:

4a Kobayashi S. Ishitani H. Chem. Rev.  1999,  99:  1069 

4b Brunel JM. Recent Res. Dev. Org. Chem.  2003,  7:  155 

4c Liu P. Jiang H.-F. Chin. J. Org. Chem.  2004,  24:  1317 

Recent literature on heterogeneous Pd asymmetric hydrogenation:

5a Studer M. Blaser H.-U. Exner C. Adv. Synth. Catal.  2003,  345:  45 

5b Tungler A. Fogassy G. J. Mol. Catal. A: Chem.  2001,  173:  231 

5c Blaser H.-U. Indolese A. Schnyder A. Steiner H. Studer M. J. Mol. Catal. A: Chem.  2001,  173:  3 

5d Li C. Catal. Rev.  2004,  46:  419 

5e Glorius F. Spielkamp N. Holle S. Goddard R. Lehmann CW. Angew. Chem. Int. Ed.  2004,  43:  2850 

5f Raynor SA. Thomas JM. Raja R. Johnson BFG. Bell RG. Mantle MD. Chem. Commun.  2000,  1925 

6a Abe H. Amii H. Uneyama K. Org. Lett.  2001,  3:  313 

6b Suzuki A. Mae M. Amii H. Uneyama K. J. Org. Chem.  2004,  69:  5132 

7 Nanayakkara P. Alper H. Chem. Commun.  2003,  2384 

8 Wang Y.-Q. Lu S.-M. Zhou Y.-G. Org. Lett.  2005,  7:  3235 

9a Krzyzanowska B. Stec WJ. Synthesis  1982,  270 

9b Masumoto S. Usuda H. Suzuki M. Kainai M. Shibasaki M. J. Am. Chem. Soc.  2003,  125:  5634 

Asymmetric hydrogenation of N-diphenylphosphinyl imines:

10a Rh complex: Spindler F. Blaser H.-U. Adv. Synth. Catal.  2001,  343:  68 

10b Ir complex: Jiang X.-B. Minnaard AJ. Hessen B. Feringa BL. Duchateau ALL. Andrien JGO. Boogers JAF. de Vries JG. Org. Lett.  2003,  5:  1503 

Asymmetric reduction of N-diphenylphosphinyl imines without hydrogen:

11a Yamada T. Nagata T. Sugi K. Yorozu K. Ikeno T. Ohtsuka Y. Miyazaki D. Mukaiyama T. Chem. Eur. J.  2003,  9:  4485 

11b Hutchins RO. Magid AA. Stercho YP. Wambsgans A. J. Org. Chem.  1987,  52:  702 

11c Lipshutz BH. Shimizu H. Angew. Chem. Int. Ed.  2004,  43:  2228 

12 N-(Diphenylphosphinyl)amines 2 obtained by addition of diorganozinc to aldimines: Boezio AA. Pytkowicz J. Côté A. Charette AB. J. Am. Chem. Soc.  2003,  125:  14260 

13

A series of additives were tested in the reaction of 1b: 3 Å MS (conversion: >95%, 96.4% ee), 5 Å MS (conversion: 72%, 96.4% ee), Na₂SO₄ (conversion: 64%, 96.4% ee).

14

Asymmetric Hydrogenation; Typical Procedure. (S)-SEGPHOS (2.9 mg, 0.0048 mmol) and Pd(CF₃CO₂)₂ (1.3 mg, 0.004 mmol) were placed in a dried Schlenk tube under a nitrogen atmosphere, and degassed anhydrous acetone was added. The mixture was stirred at r.t. for 1 h. The solvent was removed under vacuum to give the catalyst. This catalyst was placed in a nitrogen-filled glove box and dissolved in anhyd TFE (1 mL). To a mixture of 1a and 4 Å MS, the catalyst solution was added, and then the mixture was transferred to an autoclave. The hydrogenation was performed at r.t. under H₂ (1000 psi) for 8-12 h. The hydrogen was carefully released and the solvents were removed. Conversion was determined by ¹H NMR spectroscopy. The ee was determined by HPLC after purification on silica gel (hexanes-EtOAc-Et₃N, 1:2:0.02). The absolute configuration of 2a was determined by measurement of its optical rotation. N-Diphenylphosphinyl imines 1 were prepared according to the literature. [9] Racemates of N-(diphenylphosphinyl)amines were prepared by reduction of the corresponding imines using NaBH₄ in THF. For the preparation of complexes and other experimental details, see reference 8.

15

Compound 1c: white solid. ¹H NMR (400 MHz, CDCl₃): δ = 2.95 (d, J = 1.8 Hz, 3 H), 7.12-7.17 (m, 2 H), 7.43-7.45 (m, 6 H), 7.94-7.99 (m, 4 H), 8.09-8.12 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 23.1 (d, J = 12.3 Hz), 115.8 (d, J = 21.7 Hz), 128.6 (d, J = 12.3 Hz), 130.6 (d, J = 8.9 Hz), 131.7, 131.8, 134.8 (d, J = 130.2 Hz), 135.9 (d, J = 25.8 Hz), 165.7 (d, J = 252.7 Hz), 180.2 (d, J = 7.0 Hz). ³¹P NMR (162 MHz, CDCl₃): δ = 19.1. HRMS (ESI): m/z calcd for C₂₀H₁₈FNOP [M + H⁺]: 338.1105; found: 338.1082.
Compound 1f: white solid. ¹H NMR (400 MHz, CDCl₃): δ = 2.95 (d, J = 2.1 Hz, 3 H), 3.88 (s, 3 H), 7.10 (m, 1 H), 7.39-7.46 (m, 7 H), 7.64 (d, J = 2.4 Hz, 2 H), 7.95-8.00 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 23.3 (d, J = 12.4 Hz), 55.6, 113.6, 117.9, 120.7, 128.6 (d, J = 12.4 Hz), 129.7, 131.6, 131.7 (d, J = 9.0 Hz), 134.8 (d, J = 130.3 Hz), 141.0 (d, J = 23.9 Hz), 159.8, 181.5 (d, J = 7.5 Hz). ³¹P NMR (162 MHz, CDCl₃): δ = 19.3. HRMS (ESI): m/z calcd for C₂₁H₂₁NO₂P [M + H⁺]: 350.1304; found: 350.1297.
Compound 1g: white solid. ¹H NMR (400 MHz, CDCl₃): δ = 2.89 (d, J = 2.0 Hz, 3 H), 3.82 (d, J = 2.4 Hz, 3 H), 6.93 (d, J = 8.3 Hz, 1 H), 7.00 (s, 1 H), 7.40-7.45 (m, 7 H), 7.63 (dd, J = 1.7, 7.6 Hz, 1 H), 7.93-7.99 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 28.3 (d, J = 13.6 Hz), 55.5, 111.6, 120.6, 128.4 (d, J = 12.3 Hz), 129.9, 131.4, 131.8 (d, J = 8.9 Hz), 132.3, 134.9 (d, J = 129.2 Hz), 158.0, 186.0 (d, J = 7.6 Hz). ³¹P NMR (162 MHz, CDCl₃): δ = 18.5. HRMS (ESI): m/z calcd for C₂₁H₂₁NO₂P [M + H⁺]: 350.1304; found: 350.1288.
Compound 2a: white solid; 95.3% ee (R); [α]_D ²⁶ +38.3 (c 0.54, EtOH); R _f 0.14 (PE-EtOAc, 2:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 20:80, 1.0 mL/min, 254 nm): t _R 12.9 min (R), t _R 24.4 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.58 (d, J = 6.7 Hz, 3 H), 3.17 (dd, J = 5.9, 9.1 Hz, 1 H), 4.36-4.43 (m, 1 H), 7.26-7.45 (m, 11 H), 7.80-7.85 (m, 2 H), 7.89-7.93 (m, 2 H).
Compound 2b: white solid; 96.6% ee (S); [α]_D ⁸ -66.5 (c 1.08, MeOH); R _f 0.22 (PE-EtOAc, 2:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80-20, 1.0 mL/min, 254 nm): t _R 11.4 min (R), t _R 15.8 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.56 (d, J = 6.8 Hz, 3 H), 2.34 (s, 3 H), 3.14-3.17 (m, 1 H), 4.32-4.39 (m, 1 H), 7.15 (dd, J = 8.0, 20.4 Hz, 4 H), 7.37-7.48 (m, 6 H), 7.81-7.91 (m, 4 H).
Compound 2c: white solid; 94.0% ee (S); [α]_D ⁸ -41.9 (c 1.04, MeOH); R _f 0.18 (PE-EtOAc, 2:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 10.0 min (R), t _R 27.0 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.55 (d, J = 6.8 Hz, 3 H), 3.11 (dd, J = 5.9, 9.2 Hz, 1 H), 4.35-4.42 (m, 1 H), 6.98 (t, J = 8.7 Hz, 2 H), 7.23-7.25 (m, 2 H), 7.36-7.37 (m, 2 H), 7.44-7.46 (m, 4 H), 7.78-7.81 (m, 2 H), 7.88-7.92 (m, 2 H).
Compound 2d: white solid; 94.2% ee (S); [α]_D ⁸ -73.4 (c 1.14, MeOH); R _f 0.33 (PE-EtOAc, 1:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 11.4 min (R), t _R 26.3 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.55 (d, J = 6.8 Hz, 3 H), 3.17 (dd, J = 5.7, 9.5 Hz, 1 H), 4.33-4.40 (m, 1 H), 7.24 (dd, J = 8.5, 23.0 Hz, 4 H), 7.37-7.47 (m, 6 H), 7.79 (dd, J = 7.0, 12.0, 2 H), 7.90 (dd, J = 6.9, 11.9 Hz, 2 H).
Compound 2e: white solid; 96.0% ee (S); [α]_D ⁸ -66.4 (c 1.30, MeOH); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 15.9 min (R), t _R 26.8 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.55 (d, J = 6.7 Hz, 3 H), 3.12 (dd, J = 5.9, 9.4 Hz, 1 H), 3.80 (s, 3 H), 4.31-4.41 (m, 1 H), 6.85 (d, J = 8.7 Hz, 2 H), 7.21 (d, J = 8.7 Hz, 2 H), 7.37-7.48 (m, 6 H), 7.81-7.91 (m, 4 H).
Compound 2f: white solid; 96.0% ee (S); [α]_D ⁸ -52.1 (c 1.32, MeOH); R _f 0.38 (PE-EtOAc, 1:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 14.5 min (R), t _R 29.4 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.57 (d, J = 6.8 Hz, 3 H), 3.22 (dd, J = 5.9, 9.5 Hz, 1 H), 3.78 (s, 3 H), 4.31-4.39 (m, 1 H), 6.82-6.88 (m, 3 H), 7.21-7.23 (m, 1 H), 7.36-7.47 (m, 6 H), 7.80-7.93 (m, 4 H).
Compound 2g: white solid; 98.6% ee (S); [α]_D ⁸ -22.1 (c 1.13, MeOH); R _f 0.33 (PE-EtOAc, 1:1). HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 11.9 min (R), t _R 21.3 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.50 (d, J = 6.8 Hz, 3 H), 3.69 (s, 3 H), 3.87 (dd, J = 8.0, 10.5 Hz, 1 H), 4.36-4.43 (m, 1 H), 6.78-6.82 (m, 2 H), 6.97 (s, 1 H), 7.19 (t, J = 7.7 Hz, 1 H), 7.33-7.38 (m, 6 H), 7.72 (dd, J = 7.3, 11.9 Hz, 2 H), 7.79 (dd, J = 7.1, 11.8 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 25.1, 49.6, 55.4, 111.2, 121.0, 128.3 (d, J = 7.0 Hz), 128.5, 131.7, 131.8, 128.1 (d, J = 108.6 Hz), 131.7, 131.8, 132.0 (d, J = 9.3 Hz), 132.8 (d, J = 9.4 Hz), 133.0, 133.1, 133.8 (d, J = 119.7 Hz), 157.0. ³¹P NMR (162 MHz, CDCl₃): δ = 22.9. HRMS (ESI): m/z calcd for C₂₁H₂₃NO₂P [M + H⁺], 352.1461; found, 352.1451.
Compound 2h: white solid; 86.7% ee (S); [α]_D ⁸ -38.5 (c 1.26, MeOH); R _f 0.31 (PE-EtOAc, 1:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 9.6 min (R), t _R 17.7 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 0.79 (t, J = 7.4 Hz, 3 H), 1.80-1.89 (m, 1 H), 1.97-2.04 (m, 1 H), 3.25 (dd, J = 6.4, 9.4 Hz, 1 H), 4.08-4.11 (m, 1 H), 7.14-7.16 (m, 2 H), 7.23-7.33 (m, 5 H), 7.42-7.44 (m, 4 H), 7.73-7.87 (m, 4 H).
Compound 2i: white solid; 92.8% ee (S); [α]_D ⁸ -77.8 (c 1.02, MeOH); R _f 0.39 (PE-EtOAc, 1:1); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 21.6 min (R), t _R 27.7 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.66 (d, J = 6.7 Hz, 3 H), 3.27-3.31 (m, 1 H), 4.51-4.61 (m, 1 H), 7.32-7.33 (m, 2 H), 7.43-7.48 (m, 7 H), 7.65 (s, 1 H), 7.80-7.83 (m, 5 H), 7.93 (m, 2 H).
Compound 2j: white solid, 87.0% ee (S), [α]_D ⁸ -42.1 (c 0.60, CH₂Cl₂); R _f 0.34 (PE-CH₂Cl₂,1:4); HPLC (Chiralpak AS-H column, hexane-i-PrOH, 80:20, 1.0 mL/min, 254 nm): t _R 12.1 min (R), t _R 17.0 min (S). ¹H NMR (400 MHz, CDCl₃): δ = 1.60 (d, J = 6.8 Hz, 3 H), 3.19 (dd, J = 6.6, 10.3 Hz, 1 H), 4.38-4.44 (m, 1 H), 6.13 (d, J = 3.2 Hz, 1 H), 6.28 (dd, J = 1.9, 3.2 Hz, 1 H), 7.35 (m, 1 H), 7.42-7.49 (m, 6 H), 7.87-7.95 (m, 4 H).