Enantioselective Synthesis of β-Nitro Phosphonates Catalyzed by a Secondary Amine Bisthiourea

Abstract

An enantioselective Michael addition of diphenyl phosphonate to nitroalkenes has been developed by using a secondary amine bisthiourea catalyst to access enantiomerically enriched β-nitro phosphonates. In this reaction, molecular sieves play a key role in achieving high and reproducible yields with a high enantioselectivities of up to 99% at –10 °C. A probable mechanism for the enantioselective Michael addition reaction was established by means of an NMR spectroscopic study.

Key words,

asymmetric synthesis - nitroalkenes - nitro phosphonates - diphenyl phosphonate - organocatalysis - Michael addition

• References


For reviews on the syntheses and applications of α-amino phosphonic acids, see:
• 1a Hannour S. Ryglowski A. Roumestant ML. Viallefont P. Martinez J. Ouazzani F. El Hallaoui A. Phosphorus, Sulfur Silicon Relat. Elem. 1998; 134: 419
• 1b Lefebvre IM. Evans SA. Phosphorus, Sulfur Silicon Relat. Elem. 1999; 144: 397
• 1c Gröger H. Hammer B. Chem. Eur. J. 2000; 6: 943

For reviews on the syntheses and applications of β-amino phosphonic acids, see:
• 2a Palacios F. Alonso C. de los Santos JM. In Enantioselective Synthesis of β-Amino Acids . Juaristi E. Soloshonok VA. Wiley; New York: 2005. 2nd ed. 277
• 2b Palacios F. Alonso C. de los Santos JM. Chem. Rev. 2005; 105: 899
• 3 Nazish M. Saravanan S. Khan N.-uH. Kumari P. Kureshy RI. Abdi SH. R. Bajaj HC. ChemPlusChem 2014; 79: 1753
• 4 Nazish M. Jakhar A. Khan N.-uH. Verma S. Kureshy RI. Abdi SH. R. Bajaj HC. Appl. Catal., A 2016; 515: 116

For reviews on the biological activity of β-amino phosphonic acids, see:
• 5a Hiratake J. Oda J. Biosci., Biotechnol., Biochem. 1997; 61: 211
• 5b Aminophosphonic and Aminophosphinic Acids: Chemistry and Biological Activity. Kukhar VP. Hudson HR. Wiley; Chichester: 2000
• 6a Pudovik AN. Konovalova IV. Synthesis 1979; 81
• 6b Enders D. Saint-Dizier A. Lannou MI. Lenzen A. Eur. J. Org. Chem. 2006; 29
• 7a Paulsen H. Greve W. Chem. Ber. 1973; 106: 2114
• 7b Yamamoto H. Hanaya T. Kawamoto H. Inokawa S. Yamashita M. Armour MA. Nakashima TT. J. Org. Chem. 1985; 50: 3516
• 7c Pachamuthu K. Figueroa-Perez I. Ali IA. I. Schmidt RR. Eur. J. Org. Chem. 2004; 3959
• 7d Enders D. Tedeschi L. Bats JW. Angew. Chem. Int. Ed. 2000; 39: 4605
• 7e Enders D. Tedeschi L. Förster D. Synthesis 2006; 1447
• 8 Rai V. Namboothiri IN. N. Tetrahedron: Asymmetry 2008; 19: 2335
• 9 Kuchurov IV. Nigmatov AG. Kryuchkova EV. Kostenko AA. Kucherenkoa AS. Zlotin SG. Green Chem. 2014; 16: 1521
• 10 Sohtome Y. Horitsugi N. Takagi R. Nagasawa K. Adv. Synth. Catal. 2011; 353: 2631
• 11 Wang J. Heikkinen LD. Liansuo ZH. L. Jiang W. Xie H. Wang W. Adv. Synth. Catal. 2007; 349: 1052
• 12 Terada M. Ikehara T. Ube H. J. Am. Chem. Soc. 2007; 129: 14112

For reviews on organocatalytic enantioselective conjugate addition reactions, see:
• 13a Almaşi D. Alonso DA. Nájera C. Tetrahedron: Asymmetry 2007; 18: 299
• 13b Tsogoeva SB. Eur. J. Org. Chem. 2007; 1701
• 13c Vicario JL. Badia D. Carrillo L. Synthesis 2007; 2065

Metal-free enantioselective Michael addition reactions of other phosphorus nucleophiles have been reported: for diaryl phosphine/phosphine oxide addition to nitroalkenes, see:
• 14a Bartoli G. Bosco M. Carlone A. Locatelli M. Mazzanti A. Sambri L. Melchiorre P. Chem. Commun. 2007; 722
• 14b Fu X. Jiang Z. Tan C. Chem. Commun. 2007; 5058

for hydrophosphination/phosphonylation of α,β-unsaturated aldehydes, see:
• 14c Carlone A. Bartoli G. Bosco M. Sambri L. Melchiorre P. Angew. Chem. Int. Ed. 2007; 46: 4504
• 15 Zhu Y. Malerich JP. Rawal VH. Angew. Chem. Int. Ed. 2010; 49: 153
• 16 Alcaine A. Marqués-López E. Merino P. Tejeroa T. Herrera RP. Org. Biomol. Chem. 2011; 9: 2777
• 17 Abbaraju S. Bhanushali M. Zhao C.-G. Tetrahedron 2011; 67: 7479
• 18 Etter MC. Urbañczyk-Lipkowska Z. Zia-Ebrahimi M. Panunto TW. J. Am. Chem. Soc. 1990; 112: 8415
• 19 Etter MC. Reutzel SM. J. Am. Chem. Soc. 1991; 113: 2586
• 20 Etter MC. Acc. Chem. Res. 1990; 23: 120
• 21 Thadani AN. Stankovich AR. Rawal VH. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 5846
• 22 Curran DP. Kuo LH. J. Org. Chem. 1994; 59: 3259
• 23 Curran DP. Kuo LH. Tetrahedron Lett. 1995; 36: 6647
• 24 Schuster T. Kurz M. Göbel MW. J. Org. Chem. 2000; 65: 1697
• 25 Schreiner PR. Wittkopp A. Org. Lett. 2002; 4: 217
• 26 Vachal P. Jacobsen EN. J. Am. Chem. Soc. 2002; 124: 10012
• 27 Vachal P. Jacobsen EN. Org. Lett. 2000; 2: 867
• 28 Sigman MS. Vachal P. Jacobsen EN. Angew. Chem. Int. Ed. Engl. 2000; 39: 1279
• 29 Sigman MS. Jacobsen EN. J. Am. Chem. Soc. 1998; 120: 4901
• 30 Wenzel AG. Jacobsen EN. J. Am. Chem. Soc. 2002; 124: 12964
• 31 Wenzel AG. Lalonde MP. Jacobsen EN. Synlett 2003; 1919
• 32 Schuster T. Bauch M. Dürner G. Göbel MW. Org. Lett. 2000; 2: 179
• 33 McDougal NT. Schaus SE. J. Am. Chem. Soc. 2003; 125: 12094
• 34 Okino T. Hoashi Y. Takemoto Y. J. Am. Chem. Soc. 2003; 125: 12672
• 35 Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Tetrahedron Lett. 2004; 45: 5589
• 36a Huang Y. Unni AK. Thadani AN. Rawal VH. Nature 2003; 424: 146
• 36b McGilvra JD. Unni AK. Modi K. Rawal VH. Angew. Chem. Int. Ed. 2006; 45: 6130
• 36c Gondi VB. Hagihara K. Rawal VH. Angew. Chem. Int. Ed. 2009; 48: 776

For reviews on hydrogen-bond donor catalysis, see:
• 37a Doyle AG. Jacobsen EN. Chem. Rev. 2007; 107: 5713
• 37b McGilvra JD. Gondi VB. Rawal VH. In Enantioselective Organocatalysis: Reactions and Experimental Procedures . Dalko PI. Wiley-VCH; Weinheim: 2007. Chap. 6 189
• 37c Ting A. Schaus SE. Eur. J. Org. Chem. 2007; 5797
• 37d Yu X. Wang W. Chem. Asian J. 2008; 3: 516
• 38 Rampalakosa C. Wulff W. D. 2008; 350: 1785
• 39 Doherty S. Knight JG. Bell AL. El-Menabawey S. Vogels CM. Decken A. Westcott SA. Tetrahedron: Asymmetry 2009; 20: 1437
• 40 Serdyuk OV. Heckel CM. Tsogoeva SB. Org. Biomol. Chem. 2013; 11: 7051
• 41 Diphenyl [(1R)-2-Nitro-1-phenylethyl]phosphonate (4a); Typical Procedure Phosphonate 2a (0.22 mmol, 43 μL) was added to a stirred mixture of bisthiourea 3g (0.010 mol%, 6.5 mg), nitrostyrene 1a (0.20 mmol, 30 mg), and 4 Å MS (60 mg) in CH₂Cl₂ (1 mL). The mixture was then stirred at –10 °C for 2 h until the reaction was complete (TLC). The resulting mixture was purified directly by column chromatography [silica gel, hexane–EtOAc (95:5)] to give a white solid; yield: 72.0 mg (98%; 92% ee); mp 130–136 °C; [α]_D ²⁷ –1.8° (c 1.0, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 7.45 (dd, J = 5.5, 3.8 Hz, 2 H), 7.37 (m, 3 H), 7.31 (t, J = 7.9 Hz, 2 H), 7.19 (m, 3 H), 7.09 (m, 3 H), 6.74 (d, J = 7.9 Hz, 2 H), 5.20 (ddd, J = 13.7, 7.3, 4.5 Hz, 1 H), 5.12 (ddd, J = 13.9, 11.0, 7.6 Hz, 1 H), 4.43 (ddd, J = 24.7, 11.0, 4.4 Hz, 1 H). ¹³C NMR (150 MHz, CDCl₃): δ = 150.03, 130.70 (d, J _C–P = 7.5 Hz), 130.04, 129.77, 129.34 (d, J _C–P = 2.9 Hz), 129.00, 125.66 (d, J _C–P = 37.0 Hz), 120.47 (d, J _C–P = 4.2 Hz), 120.21 (d, J _C–P = 4.1 Hz), 75.03 (d, J _C–P = 5.0 Hz), 43.94, 43.00. HPLC: CHIRALPAK ASH [hexane–i-PrOH (85:15), 0.5 mL/min (λ = 220 nm), 25 °C]: T_r (minor) = 20.8 min; T_r (major) = 26.7 min.
• 42 Guang J. Zhao JC.-G. Tetrahedron Lett. 2013; 54: 5703
• 43 (R)-diphenyl(1-(3-Chlorophenyl)-2-nitroethyl) phosphonate (4g): ¹H NMR (600 MHz,) δ = 7.43 (d, J= 1.8, 1H), 7.32 (m, 5H), 7.22 (m, 3H), 7.11 (dd, J= 18.6, 7.8, 3H), 6.82 (d, J= 8.2, 2H), 5.19 (ddd, J= 14.0, 7.2, 4.3, 1H), 5.08 (ddd, J= 14.0, 11.1, 7.1, 1H), 4.39 (ddd, J= 24.7, 11.1, 4.2, 1H).;¹³C NMR (150 MHz,) δ = 150.01, 135.20, 132.86, 129.88, 127.40, 125.84 (d, J _C-P= 31.0), 120.20, 74.74, 43.57, 42.64. CHIRALPAK ASH column, hexane/2-propanol = 75:25, flow rate 0.5 ml/ min^-1, λ = 220 nm, 25^oC, tr₁ (minor) = 14.0 min, tr₂ (major) = 20.6 min, 87% ee, [α]_D ²⁷ = -3.8 (c = 1.0 in CHCl₃), white solid, mp 95 - 100^oC; HRMS (ESI) Calcd. for C₂₀H₁₈ClNO₅P [M+H]⁺ 418.0611, found 418.0607.