Bifunctional Iminophosphorane Catalyzed Enantioselective Ketimine Phospha-Mannich Reaction

Dedicated to Professor Steven V. Ley on the occasion of his 70^th birthday

Abstract

The enantioselective phospha-Mannich reaction of diethyl phosphite to unactivated N-DPP-protected ketimines catalyzed by a bifunctional iminophosphorane (BIMP) superbase organocatalyst is described. The reaction is applicable to ketimines bearing electron-rich and electron-poor aryl substituents and occurs with excellent yields and moderate enantioselectivities under mild reaction conditions.

Key words

asymmetric catalysis - bifunctional organocatalysis - phospha-Mannich - ketimine - superbase

• References and Notes

• 1a Hiratake J, Oda J. Biosci., Biotechnol., Biochem. 1997; 61: 211
• 1b Aminophosphonic and Aminophosphinic Acids . Kukhar VP, Hudson HR. John Wiley & Sons; New York: 2000
• 2a Allen JG, Atherton FR, Hall MJ, Hassal CH, Holmes SW, Lambert RW, Nisbet LJ, Ringrose PS. Nature (London) 1978; 272: 56
• 2b Atherton FR, Hassall CH, Lambert RW. J. Med. Chem. 1986; 29: 29
• 2c Stowasser B, Budt K.-H, Jian-Qi L, Peyman A, Ruppert D. Tetrahedron Lett. 1992; 33: 6625
• 2d Alonso E, Solis A, del Pozo C. Synlett 2000; 698
• 2e Hirschmann R, Smith AB. III, Taylor CM, Benkovic PA, Taylor SD, Yager KM, Sprengeler PA, Benkovic SJ. Science 1994; 265: 234
• 2f Smith WW, Bartlett PA. J. Am. Chem. Soc. 1998; 120: 4622
• 3a Enders D, Saint-Dizier A, Lannou M.-I, Lenzen A. Eur. J. Org. Chem. 2006; 29
• 3b Ordóñez M, Rojas-Cabrera H, Cativiela C. Tetrahedron 2009; 65: 17
• 3c Albrecht L, Albrecht A, Krawczyk H, Jørgensen KA. Chem. Eur. J. 2010; 16: 28
• 3d Bera K, Namboothiri IN. N. Asian J. Org. Chem. 2014; 3: 1234
• 3e Kolodiazhnyi OI, Kukhar VP, Kolodiazhna AO. Tetrahedron: Asymmetry 2014; 25: 865
• 3f Faisca Phillips AM. Mini-Rev. Org. Chem. 2014; 11: 164
• 3g Dziegielewski M, Pieta J, Kaminska E, Albrecht L. Eur. J. Org. Chem. 2015; 677
• 4a Merino P, Marqués-López E, Herrera RP. Adv. Synth. Catal. 2008; 350: 1195
• 4b Angelini T, Bonollo S, Lanari D, Pizzo F, Vaccaro L. Org. Biomol. Chem. 2013; 11: 5042

For reviews on organocatalysis, see:
• 5a Dalko PI, Moisan L. Angew. Chem. Int. Ed. 2004; 43: 5138
• 5b Berkessel A, Gröger H. Asymmetric Organocatalysis . Wiley-VCH; Weinheim: 2005
• 5c List B, Yang JW. Science 2006; 313: 1584
• 5d Dondoni A, Massi A. Angew. Chem. Int. Ed. 2008; 47: 4638
• 5e Bertelsen S, Jørgensen KA. Chem. Soc. Rev. 2009; 38: 2178
• 5f Palomo C, Oiarbide M, López R. Chem. Soc. Rev. 2009; 38: 632

For reviews on Brønsted base/H-bond donor bifunctional organocatalysts, see:
• 5g Takemoto Y. Org. Biomol. Chem. 2005; 3: 4299
• 5h Connon SJ. Chem. Commun. 2008; 2499
• 5i Marcelli T, Hiemstra H. Synthesis 2010; 1229
• 5j Quintavella A, Cerisoli L, Montroni E. Current Organocatalysis 2014; 1: 107

For selected examples using metals, see:
• 6a Gröger H, Saida Y, Sasai H, Yamaguchi K, Martens J, Shibasaki M. J. Am. Chem. Soc. 1998; 120: 3089
• 6b Abell JP, Yamamoto H. J. Am. Chem. Soc. 2008; 130: 10521
• 6c Huang M, Li C, Huang J, Duan W.-L, Xu S. Chem. Commun. 2012; 48: 11148

For selected examples using organocatalysts, see:
• 6d Pettersen D, Marcolini M, Bernardi L, Fini F, Herrera RP, Sgarzani V, Ricci A. J. Org. Chem. 2006; 71: 6269
• 6e Joly GD, Jacobsen EN. J. Am. Chem. Soc. 2004; 126: 4102
• 6f Akiyama T, Morita H, Itoh J, Fuchibe K. Org. Lett. 2005; 7: 2583
• 6g Nakamura S, Nakashima H, Sugimoto H, Sano H, Hattori M, Shibata N, Toru T. Chem. Eur. J. 2008; 14: 2145
• 6h Fu X, Loh W.-T, Zhang Y, Chen T, Ma T, Liu H, Wang J, Tan C.-H. Angew. Chem. Int. Ed. 2009; 48: 7387
• 7a Riant O, Hannedouche J. Org. Biomol. Chem. 2007; 5: 873
• 7b Shibasaki M, Kanai M. Chem. Rev. 2008; 108: 2853
• 8a Yin L, Bao Y, Kumagai N, Shibasaki M. J. Am. Chem. Soc. 2013; 135: 10338
• 8b Nakamura S, Hayashi M, Hiramatsu Y, Shibata N, Funahashi Y, Toru T. J. Am. Chem. Soc. 2009; 131: 18240
• 8c Kumar A, Sharma V, Kaur J, Kumar V, Mahajan S, Kumar N, Chimni SS. Tetrahedron 2014; 70: 7044
• 8d George J, Sridhar B, Reddy BV. S. Org. Biomol. Chem. 2014; 12: 1595
• 9a Núñez MG, Farley AJ. M, Dixon DJ. J. Am. Chem. Soc. 2013; 135: 16348
• 9b Goldys AM, Núñez MG, Dixon DJ. Org. Lett. 2014; 16: 6294
• 9c Goldys AM, Dixon DJ. Macromolecules 2014; 47: 1277
• 10a Ishikawa T. Superbases for Organic Synthesis: Guanidines, Amidines, Phosphazenes and Related Organocatalysts. Wiley; New York: 2009

For a review on chiral organosuperbases, see:
• 10b Ishikawa T, Kumamoto T. Synthesis 2006; 737
• 10c Leow D, Tan C.-H. Chem. Asian J. 2009; 4: 488
• 10d Leow D, Tan C.-H. Synlett 2010; 1589
• 10e Ishikawa T. Chem. Pharm. Bull. 2010; 58: 1555
• 10f Fu X, Tan C.-H. Chem. Commun. 2011; 47: 8210
• 10g Selig P. Synthesis 2013; 45: 703
• 10h Krawczyk H, Dzięgielewski M, Deredas D, Albrecht A, Albrecht Ł. Chem. Eur. J. 2015; 21: 10268

For recent selected examples, see:
• 10i Nugent BM, Yoder RA, Johnston JN. J. Am. Chem. Soc. 2004; 126: 3418
• 10j Terada M, Ube H, Yaguchi Y. J. Am. Chem. Soc. 2006; 128: 1454
• 10k Uraguchi D, Sakaki S, Ooi T. J. Am. Chem. Soc. 2007; 129: 12392
• 10l Sohtome Y, Shin B, Horitsugi N, Takagi R, Noguchi K, Nagasawa K. Angew. Chem. Int. Ed. 2010; 49: 7299
• 10m Fu X, Tan C.-H. Chem. Commun. 2011; 47: 8210
• 10n Bandar JS, Lambert TH. J. Am. Chem. Soc. 2012; 134: 5552
• 10o Takeda T, Terada M. J. Am. Chem. Soc. 2013; 135: 15306
• 10p Işik M, Unver MY, Tanyeli C. J. Org. Chem. 2015; 80: 828
• 10q Gao X, Han J, Wang L. Org. Lett. 2015; 17: 4596
• 11 Zhu QA, Lu YX. Angew. Chem. Int. Ed. 2010; 49: 7753
• 12 Wittkopp A, Schreiner PR. Chem. Eur. J. 2003; 9: 407
• 13 Representative Procedure for the Enantioselective Ketimine Phospha-Mannich Reaction: To a solution of ketimine 2a (128 mg, 0.40 mmol, 2.0 equiv) and catalyst 1b (15 mg, 0.020 mmol, 0.10 equiv in 4.0 mL of diethyl ether) was added diethyl phosphite 3 (26 μL, 0.20 mmol, 1.0 equiv) at rt. Stirring was maintained for 24 h whereupon the crude reaction mixture was purified directly by flash column chromatography [petroleum ether to petroleum ether–EtOAc (1:2), EtOAc then EtOAc–MeOH (9:1)] to afford the phospha-Mannich addition product 4a. Diethyl {(1S)-1-[(Diphenylphosphoryl)amino]-1-phenylethyl}-phosphonate (4a): The title compound 4a was isolated in 99% yield (91 mg) and 58% ee as a colorless solid. ¹H NMR (500 MHz, CDCl₃): δ = 1.03 (t, J = 7.0 Hz, 3 H), 1.25 (t, J = 7.0 Hz, 3 H), 1.82 (d, J _PH = 17.0 Hz, 3 H), 3.53 (ddq, J = 10.0, 7.0, 7.0 Hz, 1 H), 3.81 (ddq, J = 10.0, 7.0, 7.0 Hz, 1 H), 4.03–4.20 (m, 3 H), 7.18–7.30 (m, 5 H), 7.31–7.47 (m, 4 H), 7.51 (dd, J = 7.5, 1.5 Hz, 2 H), 7.55–7.64 (m, 2 H), 7.82–7.91 (m, 2 H). ³¹P NMR (162 MHz, CDCl₃): δ = 20.1 (J _PP = 29.3 Hz), 24.8 (J _PP = 29.3 Hz). HRMS: (ESI⁺): m/z calcd for C₂₄H₂₉NNaO₄P₂: 480.1464; found: 480.1454. See Supporting Information for full characterization data.