Asymmetric Synthesis of Substituted α-Amino Phosphonates with Chiral Crown Ethers as Catalysts

Abstract

A simple, phase-transfer catalytic synthesis of enantioenriched phosphonoglutaminic acid derivatives (ee up to 86%) has been developed by using ‘sugar-based’ crown ether catalysts.

Key words

Michael additions - asymmetric catalysis - chiral phase-transfer catalysis - chiral crown compounds - aminophosphonates

References and Notes

• 1 Oleksyszyn J. In Aminophosphonic and Aminophosphinic Acids   Kukhar VP. Hudson HR. John Wiley and Sons; Chichester: 2000.  Chap.15. p.537-558  
• 2 Kafarski P. Lejczak B. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  63:  193 
• 3a Atherton FR. Hassall CH. Lambert RW. J. Med. Chem.  1986,  29:  29 
• 3b Lejczak B. Kafarski P. Zygmunt J. Biochemistry  1989,  28:  3549 
• 4a Allen MC. Fuhrer W. Tuck B. Wade R. Wood JM. J. Med. Chem.  1989,  32:  1652 
• 4b Rozenfeld R. Iturrioz X. Okada M. Maigret B. Llorens-Cortes C. Biochemistry  2003,  42:  14785 
• 5 Abdel-Meguid SS. Zhao B. Murthy KHM. Winborne E. Choi JK. DesJarlais RL. Minnich MD. Culp JS. Debouck C. Biochemistry  1993,  32:  7972 
• 6a Smith AB. Taylor CM. Benkovic SJ. Hirschman R. Tetrahedron Lett.  1994,  35:  6853 
• 6b Tanaka F. Kinoshita K. Tanimura R. Fuji I. J. Am. Chem. Soc.  1996,  118:  2332 
• 7a Matczak-Jon E. Kurzak B. Sawka-Dobrowska W. Kafarski P. Lejczak B. J. Chem. Soc., Dalton Trans.  1996,  3455 
• 7b Kim WD. Kiefer GE. Huskens J. Sherry AD. Inorg. Chem.  1997,  36:  4128 
• 8 Ordónez M. Rojas-Cabrera H. Cativiela C. Tetrahedron  2009,  65:  17 
• 9a Smith AB. Yager KM. Taylor CM. J. Am. Chem. Soc.  1995,  117:  10879 
• 9b Mikolajczyk M. Lyzwa P. Drabowicz J. Tetrahedron: Asymmetry  1997,  8:  3991 
• 9c Lefebvre IM. Evans SA. J. Org. Chem.  1997,  62:  7532 
• 9d Davis FA. Lee S. Yan H. Titus DD. Org. Lett.  2001,  3:  1757 
• 10a Schöllkopf U. Schütze R. Liebigs Ann. Chem.  1987,  45 
• 10b Groth U. Richter L. Schöllkopf U. Liebigs Ann. Chem.  1992,  903 
• 11 Sasai H. Arai S. Tahara Y. Shibasaki M. J. Org. Chem.  1995,  60:  6656 
• 12 Pettersen D. Marcolini M. Bernardi L. Fini F. Herrera RP. Sgarzani V. Ricci A. J. Org. Chem.  2006,  71:  6269 
• 13 Joly GD. Jacobsen EN. J. Am. Chem. Soc.  2004,  126:  4102 
• 14 Jászay ZM. Németh G. Truong SP. Petneházy I. Grûn A. Tõke L. Tetrahedron: Asymmetry  2005,  16:  3837 
• 15a Alonso-López M. Martin-Lomas M. Penades S. Tetrahedron Lett.  1986,  27:  3551 
• 15b Van Maarschalkerwaart DAH. Willard NP. Pandit UK. Tetrahedron  1992,  48:  8825 
• 15c Kanakamma PP. Mani NS. Maitra U. Nair V. J. Chem. Soc., Perkin Trans.1  1995,  2339 
• 16a Bakó P. Szöllõsy . Bombicz P. Tõke L. Synlett  1997,  291 
• 16b Bakó T. Bakó P. Szöllõsy . Czugler M. Keglevich G. Tõke L. Tetrahedron: Asymmetry  2002,  13:  203 
• 16c Bakó T. Bakó P. Keglevich G. Báthori N. Czugler M. Tatai J. Novák T. Parlagh G. Tõke L. Tetrahedron: Asymmetry  2003,  14:  1917 

17

Preparation of Compounds 2; General Procedure: The stirred mixture of the Schiff base 1 (0.5 g, 1.5 mmol), crown ether 4 (0.15 mmol) and t-BuONa (0.192 g, 2 mmol) in anhyd toluene (7 mL) was cooled to -78 ˚C under an argon atmosphere. This was left stirring for 10 min after which the toluene solution (3 mL) of the acrylic compound 3 (1.8 mmol) was added. After stirring for the given time at -78 ˚C the reaction was quenched with sat. NH₄Cl and extracted with toluene. The combined organic extracts were dried with MgSO₄, and toluene was evaporated. Product 2 was isolated by column chromatography on silica gel using EtOAc-hexane (7:3) as eluent. Crown ether 4 was also recovered during the column chromatography.
Compound 2a: for physical and spectral data see ref. 14.
Compound 2b: colorless oil. HPLC conditions: hexane- i-PrOH (95:5), flow rate: 1 mL/min, λ = 256 nm, 20 ˚C, major diastereomer: t _{R ( major)} = 6.8 min and t _{R ( minor)} = 12.8 min; minor diastereomer: t _{R ( major)} = 9.1 min and t _{R ( minor)} = 65.1 min. Major Diastereomer: ^¹H NMR (500 MHz, CDCl₃, TMS): δ = 0.81 (d, J = 8.0 Hz, 3 H), 1.28-1.38 (m, 6 H), 1.36 (s, 9 H), 1.80-2.40 (m, 1 H), 2.22-2.40 (m, 1 H), 2.40-2.51 (m, 1 H), 3.90-4.01 (m, 1 H), 4.04-4.26 (m, 4 H), 7.30-7.83 (m, 10 H). ^¹³C NMR (60 MHz, CDCl₃, TMS):
δ = 16.56 (OEt), 16.63 (OEt), 18.92 (CHMe), 28.04 (t-Bu), 34.73 (d, J _PC = 4.6 Hz, CH₂), 37.40 (d, J _PC = 15.0 Hz, CHMe), 59.52 (d, J _PC = 158.0 Hz, CHP), 62.37 (d, J _PC = 6.6 Hz, POCH₂Me), 62.60 (t-BuO), 62.71 (d, J _PC = 6.7 Hz, POCH₂Me), 127.99 (Ph), 128.41 (Ph), 128.45 (Ph), 128.57 (Ph), 128.71 (Ph), 128.84 (Ph), 128.86 (Ph), 128.93 (Ph), 130.18 (Ph), 130.28 (Ph), 135.70 (Ph), 135.74 (Ph), 139.53 (Ph), 139.58 (Ph), 170.88 (CN), 175.56 (CO). ^³¹P NMR (121 MHz, CDCl₃, H₃PO₄): δ = 24.4. Minor Diastereomer: ^¹H NMR (500 MHz, CDCl₃, TMS): δ = 1.12 (δ, J = 6.8 Hz, 3 H), 1.28-1.38 (m, 6 H), 1.27 (s, 9 H), 1.80-2.40 (m, 1 H), 2.22-2.40 (m, 1 H), 2.40-2.51 (m, 1 H), 3.90-4.01 (m, 1 H), 4.04-4.26 (m, 4 H), 7.30-7.83 (m, 10 H). ^¹³C NMR (60 MHz, CDCl₃, TMS): δ = 16.61 (OEt), 16.72 (OEt), 18.92 (CHMe), 27.97 (t-Bu), 35.16 (d, J _PC = 4.9 Hz, CH₂), 37.74 (d, J _PC = 14.4 Hz, CHMe), 59.52 (d, J _PC = 158.0 Hz, CHP), 62.30 (d, J _PC = 6.6 Hz, POEt), 62.60 (t-BuO), 62.65 (d, J _PC = 6.6 Hz, POEt), 127.99 (Ph), 128.41 (Ph), 128.45 (Ph), 128.57 (Ph), 128.71 (Ph), 128.84 (Ph), 128.86 (Ph), 128.93 (Ph), 130.18 (Ph), 130.28 (Ph), 135.70 (Ph), 135.74 (Ph), 139.53 (Ph), 139.58 (Ph), 170.88 (CN), 175.56 (CO). ^³¹P NMR (121 MHz, CDCl₃, H₃PO₄): δ = 24.3. MS (ESI):
m/z [M + H]⁺ calcd for C₂₆H₃₇NO₅P: 474.24039; found: 474.24005.
Compound 2c: colorless oil. HPLC conditions: hexane-
i-PrOH (90:10), flow rate: 1 mL/min, λ = 220 nm, 10 ˚C, major diastereomer: t _{R ( major)} = 14.1 min and t _{R ( minor)} = 17.7 min; minor diastereomer: t _{R ( major)} = 60.3 min and t _{R ( minor)} = 75.3 min. Major Diastereomer: ^¹H NMR (500 MHz, CDCl₃, TMS): δ = 1.058 (t, J = 7.1 Hz, 3 H), 1.063 (t, J = 7.0 Hz, 3 H), 3.11 (s, 3 H), 3.45-3.55 (m, 2 H), 3.82-4.12 (m, 6 H), 6.95-7.41 (m, 15 H). ^¹³C NMR (60 MHz, CDCl₃, TMS): δ = 16.42, 16.46 (OEt), 35.41 (CH₂CO₂Me), 43.55 (d, J _PC = 3.3 Hz, CHPh), 51.58 (OMe), 60.11 (d, J _PC = 132.0 Hz, CHP), 62.51 (d, J _PC = 6.4 Hz, POEt), 62.55 (d, J _PC = 7.1 Hz, POEt), 127.11 (Ph), 127.26 (Ph), 127.46 (Ph), 127.55 (Ph), 127.86 (Ph), 128.43 (Ph), 128.45 (Ph), 128.62 (Ph), 128.87 (Ph), 139.46 (Ph), 145.25 (Ph), 145.55 (Ph), 172.20 (CN), 172.97 (CO). ^³¹P NMR (121 MHz, CDCl₃, H₃PO₄): δ = 25.1. Minor Diastereomer: ^¹H NMR (500 MHz, CDCl₃, TMS):
δ = 1.12 (t, J = 7.0 Hz, 3 H), 1.19 (t, J = 7.0 Hz, 3 H), 3.35 (dd, J = 16.1, 4.0 Hz, 2 H), 3.41 (s, 3 H), 3.82-4.12 (m, 6 H), 6.95-7.41 (m, 15 H). ^¹³C NMR (60 MHz, CDCl₃, TMS): δ = 16.61, 16.72 (OEt), 35.68 (CH₂CO₂Me), 43.55 (d, J _PC = 3.3 Hz, CHPh), 51.68 (OMe), 64.65 (d, J _PC = 14.1 Hz, POEt), 66.51 (d, J _PC = 126.0 Hz, CHP), 127.11 (Ph), 127.26 (Ph), 127.46 (Ph), 127.55 (Ph), 127.86 (Ph), 128.43 (Ph), 128.45 (Ph), 128.62 (Ph), 128.87 (Ph), 139.46 (Ph), 145.25 (Ph), 145.55 (Ph), 172.20 (CN), 172.97 (CO). ^³¹P NMR (121 MHz, CDCl₃, H₃PO₄): δ = 22.7. MS (ESI): m/z [M + H]⁺ calcd for C₂₈H₃₃NO₅P: 494.20909; found: 494.20838.
Compound 2d: for physical and spectral data see ref. 14.
Compound 2e: colorless oil. [α]_D ^²0 14.2 (c = 0.6, CHCl₃). HPLC conditions: hexane-i-PrOH (95:5), flow rate: 1 mL/min, λ = 256 nm, 5 ˚C, major diastereomer: t _{R ( major)} = 36.5 min and t _{R ( minor)} = 22.5 min; minor diastereomer: t _{R ( major)} = 51.7 min and t _{R ( minor)} = 18.5 min. Major Diastereomer: ^¹H NMR (500 MHz, CDCl₃, TMS): δ = 1.02 (d, J = 7.0 Hz, 3 H), 1.24 (t, J = 7.0 Hz, 3 H), 1.28 (t, J = 7.1 Hz, 3 H), 1.98-2.10 (m, 1 H), 2.22-2.70 (m, 2 H), 3.88-4.00 (m, 1 H), 4.00-4.20 (m, 4 H), 7.19-7.62 (m, 10 H). ^¹³C NMR (60 MHz, CDCl₃, TMS): δ = 16.53 (OEt), 16.60 (OEt), 18.63 (Me), 23.02 (d, J _PC = 16.2 Hz, CHMe), 36.34 (d, J _PC = 4.3 Hz, CH₂), 59.14 (d, J _PC = 157.3 Hz, CHP), 62.78 (d, J _PC = 7.9 Hz, POEt), 65.40 (d, J _PC = 6.5 Hz, POEt), 122.68 (CHCN), 128.13 (Ph), 128.32 (Ph), 128.46 (Ph), 128.48 (Ph), 128.48 (Ph), 128.56 (Ph), 128.68 (Ph), 128.90 (Ph), 128.91 (Ph), 129.0 (Ph), 129.08 (Ph), 130.1 (Ph), 130.65 (Ph), 132.46 (Ph), 135.06 (Ph), 135.32 (Ph), 139.12 (Ph), 139.25 (Ph), 171.90 (CN). ^³¹P NMR (121 MHz, CDCl₃, H₃PO₄): δ = 22.8. Minor Diastereomer: ^¹H NMR (500 MHz, CDCl₃, TMS):
δ = 1.18 (d, J = 7.1 Hz, 3 H), 1.23 (t, J = 7.1 Hz, 3 H), 1.29 (t, J = 7.1 Hz, 3 H), 1.98-2.10 (m, 1 H), 2.22-2.70 (m, 2 H), 3.88-4.00 (m, 1 H), 4.00-4.20 (m, 4 H), 7.19-7.62 (m, 10 H). ^¹³C NMR (60 MHz, CDCl₃, TMS): δ = 16.53 (OEt), 16.60 (OEt), 17.70 (Me), 22.69 (d, J _PC = 15.2 Hz, CHMe), 35.94 (d, J _PC = 4.8 Hz, CH₂), 59.20 (d, J _PC = 159.1 Hz, CHP), 62.87 (d, J _PC = 4.4 Hz, POEt), 62.97 (d, J _PC = 4.0 Hz, POEt), 122.04 (CHCN), 128.13 (Ph), 128.32 (Ph), 128.46 (Ph), 128.48 (Ph), 128.48 (Ph), 128.56 (Ph), 128.68 (Ph), 128.90 (Ph), 128.91 (Ph), 129.0 (Ph), 129.08 (Ph), 130.1 (Ph), 130.65 (Ph), 132.46 (Ph), 135.06 (Ph), 135.32 (Ph), 139.12 (Ph), 139.25 (Ph), 172.61 (CN). ^³¹P NMR (121 MHz, CDCl₃, H₃PO₄): δ = 22.8. MS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₈N₂O₃P: 399.18321; found: 399.18296.