Synthesis of Polyfunctional Secondary Amines by the Reaction of Functionalized Organomagnesium Reagents with Tertiary Nitroalkanes

Abstract

Addition of polyfunctionalized aryl, heteroaryl, and tertiary alkylmagnesium reagents to tertiary nitroalkanes at 25 °C in tetrahydrofuran produces, after reductive workup with FeCl₂ and NaBH₄ in ethanol, the corresponding polyfunctional secondary amines in high yields.

Key words

secondary amines - nitroalkanes - organomagnesium reagents - amination reactions - adamantane

• References

• 1a Carey JS, Laffan D, Thomson C, Williams MT. Org. Biomol. Chem. 2006; 4: 2337
• 1b Schlummer B, Scholz U. Adv. Synth. Catal. 2004; 346: 1599
• 1c Thomas G. Medicinal Chemistry . Wiley-VCH; Weinheim: 2000
• 1d Liu S, Jiang X, Ma H, Liu MS, Jen AK.-Y. Macromolecules 2000; 33: 3514
• 1e Yu W.-L, Pei J, Huang W, Heeger AJ. Chem. Commun. 2000; 681
• 1f Bellmann E, Shaheen SE, Thayumanavan S, Barlow S, Grubbs RH, Marder SR, Kippelen B, Peyghambarian N. Chem. Mater. 1998; 10: 1668
• 1g Inada H, Yonemoto Y, Wakimoto T, Imai K, Shirota Y. Mol. Cryst. Liq. Cryst. 1996; 280: 331
• 1h D’Aprano G, Leclerc M, Zotti G, Schiavon G. Chem. Mater. 1995; 7: 33
• 2a Wanka L, Iqbal K, Schreiner PR. Chem. Rev. 2013; 113: 3516
• 2b Shokova EA, Kovalev VV. Russ. J. Org. Chem. 2012; 48: 1007
• 2c Liu J, Obando D, Liao V, Lifa T, Codd R. Eur. J. Med. Chem. 2011; 46: 1949
• 2d Lamoureux G, Artavia G. Curr. Med. Chem. 2010; 17: 2967
• 2e Valente S, Conte M, Tardugno M, Massa S, Nebbioso A, Altucci L, Mai A. ChemMedChem 2009; 4: 1411
• 2f Geldenhuys WJ, Malan SF, Bloomquist JR, Marchand AP, Van der Schyf CJ. Med. Res. Rev. 2005; 25: 21
• 2g Spasov AA, Khamidova TV, Bugaeva LI, Morozov IS. Pharm. Chem. J. 2000; 34: 1
• 3a Maiti D, Buchwald SL. J. Am. Chem. Soc. 2009; 131: 17423
• 3b Yang BH, Buchwald SL. J. Organomet. Chem. 1999; 576: 125
• 3c Wolfe JP, Wagaw S, Marcoux J.-F, Buchwald SL. Acc. Chem. Res. 1998; 31: 805
• 3d Hartwig JF. Angew. Chem. Int. Ed. 1998; 37: 2046
• 3e Driver MS, Hartwig JF. J. Am. Chem. Soc. 1996; 118: 7217
• 3f Wagaw S, Buchwald SL. J. Org. Chem. 1996; 61: 7240
• 3g Wolfe JP, Wagaw S, Buchwald SL. J. Am. Chem. Soc. 1996; 118: 7215
• 4a Ackermann L, Sandmann R, Song W. Org. Lett. 2011; 13: 1784
• 4b Desmarets C, Schneider R, Fort Y. Tetrahedron Lett. 2001; 42: 247
• 4c Lipshutz BH, Ueda H. Angew. Chem. Int. Ed. 2000; 39: 4492
• 5a Kawano T, Hirano K, Satoh T, Miura M. J. Am. Chem. Soc. 2010; 132: 6900
• 5b Klapars A, Antilla JC, Huang X, Buchwald SL. J. Am. Chem. Soc. 2001; 123: 7727
• 5c Wolter M, Klapars A, Buchwald SL. Org. Lett. 2001; 3: 3803
• 5d Shen R, Porco JA. Jr. Org. Lett. 2000; 2: 1333
• 5e Kalinin AV, Bower JF, Riebel P, Snieckus V. J. Org. Chem. 1999; 64: 2986
• 6 Kim M, Chang S. Org. Lett. 2010; 12: 1640
• 7a Castillo PR, Blackmond DG, Buchwald SL. J. Am. Chem. Soc. 2015; 137: 3085
• 7b Fors BP, Buchwald SL. J. Am. Chem. Soc. 2010; 132: 15914
• 8 Quach TD, Batey RA. Org. Lett. 2003; 5: 4397
• 9a Corpet M, Gosmini C. Synthesis 2014; 46: 2258
• 9b Sinha P, Kofink CC, Knochel P. Org. Lett. 2006; 8: 3741
• 9c Sinha P, Knochel P. Synlett 2006; 3304
• 9d Rucker RP, Whittaker AM, Dang H, Lalic G. Angew. Chem. Int. Ed. 2012; 51: 3953
• 9e Barker TJ, Jarvo ER. Angew. Chem. Int. Ed. 2011; 50: 8325
• 9f He C, Chen C, Cheng J, Liu C, Liu W, Li Q, Lei A. Angew. Chem. Int. Ed. 2008; 47: 6414
• 9g Berman AM, Johnson JS. J. Org. Chem. 2006; 71: 219
• 9h Berman AM, Johnson JS. J. Org. Chem. 2005; 70: 364
• 9i Narasaka K, Kitamura M. Eur. J. Org. Chem. 2005; 4505
• 9j Berman AM, Johnson JS. Synlett 2005; 1799
• 9k Berman AM, Johnson JS. J. Am. Chem. Soc. 2004; 126: 5680
• 9l Kitamura M, Suga T, Chiba S, Narasaka K. Org. Lett. 2004; 6: 4619
• 9m Yu Y, Srogl J, Liebeskind LS. Org. Lett. 2004; 6: 2631
• 10a Kopp F, Sapountzis I, Knochel P. Synlett 2003; 885
• 10b Waters WL, Marsh PG. J. Org. Chem. 1975; 40: 3344

For the reaction of nitroarenes with Grignard reagents, see:
• 11a Sapountzis I, Knochel P. J. Am. Chem. Soc. 2002; 124: 9390
• 11b Windler GK, Pagoria PF, Vollhardt KP. C. Synthesis 2014; 2383
• 11c Gao H, Xu QL, Yousufuddin M, Ess DH, Kürti L. Angew. Chem. Int. Ed. 2014; 53: 2701
• 11d Gao H, Ess DH, Yousufuddin M, Kürti L. J. Am. Chem. Soc. 2013; 135: 7086
• 11e Wylie L, Innocenti P, Whelligan DK, Hoelder S. Org. Biomol. Chem. 2012; 10: 4441
• 11f Dobbs A. J. Org. Chem. 2001; 66: 638
• 11g Dobbs AP, Voyle M, Whittall N. Synlett 1999; 1594
• 11h Bosco M, Dalpozzo R, Bartoli G, Palmieri G, Petrini M. J. Chem. Soc., Perkin Trans. 2 1991; 657
• 11i Barboni L, Bartoli G, Marcantoni E, Petrini M, Dalpozzo R. J. Chem. Soc., Perkin Trans. 1 1990; 2133
• 11j Bartoli G, Petrini M, Marcantoni E, Bosco M, Dalpozzo R. Tetrahedron Lett. 1990; 31: 6089
• 11k Inagaki Y, Okazaki R, Inamoto N. Bull. Chem. Soc. Jpn. 1975; 48: 3727
• 11l Yost Y, Gutmann HR, Muscoplat CC. J. Chem. Soc. C 1971; 2119
• 11m Bartoli G, Palmieri G, Bosco M, Dalpozzo R. Tetrahedron Lett. 1989; 30: 2129
• 11n Curtin DY, Kauer JC. J. Am. Chem. Soc. 1953; 75: 6041
• 12a Sämann C, Dhayalan V, Schreiner PR, Knochel P. Org. Lett. 2014; 16: 2418
• 12b Dagousset G, François C, León T, Blanc R, Dagousset ES, Knochel P. Synthesis 2014; 46: 3133
• 12c Sidduri A, Tilley JW, Fotouhi N. Synthesis 2014; 46: 430
• 13 Dhayalan V, Sämann C, Knochel P. Chem. Commun. 2015; 51: 3239
• 14a Piller FM, Metzger A, Schade MA, Haag BA, Gavryushin A, Knochel P. Chem. Eur. J. 2009; 15: 7192
• 14b Piller FM, Appukkuttan P, Gavryushin A, Helm M, Knochel P. Angew. Chem. Int. Ed. 2008; 47: 6802
• 15a Jensen AE, Dohle W, Sapountzis I, Lindsay DM, Vu VA, Knochel P. Synthesis 2002; 565
• 15b Sapountzis I, Dohle W, Knochel P. Chem. Commun. 2001; 2068
• 15c Rottländer M, Boymond L, Bérillon L, Leprêtre A, Varchi G, Avolio S, Laaziri H, Quéguiner G, Ricci A, Cahiez G, Knochel P. Chem. Eur. J. 2000; 6: 767
• 15d Abarbri M, Thibonnet J, Bérillon L, Dehmel F, Rottländer M, Knochel P. J. Org. Chem. 2000; 65: 4618
• 15e Boymond L, Rottländer M, Cahiez G, Knochel P. Angew. Chem. Int. Ed. 1998; 37: 1701
• 16 Schwertfeger H, Würtele C, Schreiner PR. Synlett 2010; 493
• 17a Druzhinin SI, Dubbaka SR, Knochel P, Kovalenko SA, Mayer P, Senyushkina T, Zachariasse KA. J. Phys. Chem. A 2013; 117: 9113
• 17b Druzhinin SI, Dubbaka SR, Knochel P, Kovalenko SA, Mayer P, Senyushkina T, Zachariasse KA. J. Phys. Chem. A 2008; 112: 2749
• 18a Molle G, Bauer P, Dubois JE. J. Org. Chem. 1982; 47: 4120
• 18b Dubois JE, Bauer P, Molle G, Daza J. C. R. Seances Acad. Sci., Ser. C 1977; 284: 146
• 19 Sarker H, Greer ML, Blacktock SC. J. Org. Chem. 1996; 61: 3177
• 20a Arnauld T, Barton DH. R, Doris E. Tetrahedron 1997; 53: 4137
• 20b Cortright SB, Huffman JC, Yoder RA, Coalter III JN, Johnston JN. Organometallics 2004; 23: 2238
• 20c Cran JW, Vidhani DV, Krafft ME. Synlett 2014; 25: 1550
• 21a Hawthorne MF, Strahm RD. J. Am. Chem. Soc. 1957; 79: 2515
• 21b Muller E, Metzger H, Fries D. Chem. Ber. 1954; 87: 1449
• 21c Yamamoto H, Momiyama N. Chem. Commun. 2005; 3514
• 22a Schenk C, Beekes ML, Van der Drift JA. M, de Boer TJ. Recl. J. R. Neth. Chem. Soc. 1980; 99: 278
• 22b Schenk C, Beekes ML, de Boer TJ. Recl. J. R. Neth. Chem. Soc. 1980; 99: 246
• 23a Kawakami T, Sugimoto T, Shibata I, Baba A, Matsuda H, Sonoda N. J. Org. Chem. 1995; 60: 2677
• 23b Viciu MS, Kelly III RA, Stevens ED, Naud F, Studer M, Nolan SP. Org. Lett. 2003; 5: 1479
• 23c Razzuk A, Biehl ER. J. Org. Chem. 1987; 52: 2619
• 24 Krasovskiy A, Knochel P. Synthesis 2006; 890