Stereoselective Synthesis of Chiral Pyrrolidine Derivatives of (+)-α-Pinene Containing a β-Amino Acid Moiety

Abstract

We report the synthesis of several enantiopure pyrrolidine derivatives containing a β-amino acid moiety. These novel chiral compounds were prepared through stereospecific chlorosulfonyl isocyanate (CSI) addition to the readily available, natural terpene (+)-α-pinene. Coupling of N-Boc-protected β-amino acid derivatives with various bulky amines and amino acids using the mixed anhydride activation method, followed by N-deprotection, afforded the corresponding chiral amino amides in good yields. Despite the severe steric hindrance anticipated in α-pinene-based heterocycles, efficient coupling of the amino amides and an amino ester with the acyl chloride of N-Cbz-protected (S)-proline provided the corresponding pyrrolidinic pinene derivatives in good yields. Moreover, a convenient synthesis of N-Cbz- and N-Boc-monoprotected (S)-prolinamine is reported.

Key words

stereoselective synthesis - chiral pool - enantiopure β-amino acids - coupling reactions - peptides

• References

• 1a Juaristi E. Introduction to Stereochemistry and Conformational Analysis. Wiley; New York: 1991
• 1b Blaser H.-U. Chem. Rev. 1992; 92: 935
• 1c Eliel EL, Wilen SH, Mander LN. Stereochemistry of Organic Compounds . Wiley; New York: 1994
• 1d Seyden-Penne J. Chiral Auxiliaries and Ligands in Asymmetric Synthesis. Wiley; New York: 1995
• 2a Brown HC, Zweifel G. J. Am. Chem. Soc. 1959; 81: 247
• 2b Midland DS, McDowell DC, Hatch RL, Tramontano A. J. Am. Chem. Soc. 1980; 102: 867
• 2c Krzemiński MP, Wojtczak A. Tetrahedron Lett. 2005; 46: 8299
• 2d Krzemiński MP, Ćwiklińska C. Tetrahedron Lett. 2011; 52: 3919
• 2e Peng F, Hall DG. J. Am. Chem. Soc. 2007; 129: 3070
• 2f Binder CM, Bautista A, Zaidlewicz M, Krzeminski MP, Oliver A, Singaram B. J. Org. Chem. 2009; 74: 2337
• 3 Panev S, Linden A, Dimitrov V. Tetrahedron: Asymmetry 2001; 12: 1313
• 4 Goldfuss B, Steigelmann M, Khan SI, Houk KN. J. Org. Chem. 2000; 65: 77
• 5 Dimitrov V, Dibrikov G, Genov M. Tetrahedron: Asymmetry 2001; 12: 1323
• 6 Rosner T, Sears PJ, Nugent WA, Blackmond DG. Org. Lett. 2000; 2: 2511
• 7 Steiner D, Sethofer SG, Goralski CT, Singaram B. Tetrahedron: Asymmetry 2002; 13: 1477
• 8 Szakonyi Z, Balázs A, Martinek TA, Fülöp F. Tetrahedron: Asymmetry 2006; 17: 199
• 9a Koneva EA, Volcho KP, Korchagina DV, Komarova NI, Kochnev AI, Salakhutdinov NF, Tolstikov AI. Russ. Chem. Bull. 2008; 57: 108
• 9b Jaworska M, Blocka E, Kozakiewicz A, Welniak M. Tetrahedron: Asymmetry 2011; 22: 648
• 9c Gavryushin A, Polborn K, Knochel P. Tetrahedron: Asymmetry 2004; 15: 2279
• 10 Frye SV, Eliel EL. J. Am. Chem. Soc. 1988; 110: 484

For selected recent reviews on organocatalysis, see:
• 11a Enders D, Grondal C, Huettl MR. M. Angew. Chem. Int. Ed. 2007; 46: 1570
• 11b MacMillan DW. C. Nature 2008; 455: 304
• 11c Dondoni A, Massi A. Angew. Chem. Int. Ed. 2008; 47: 4638
• 11d Melchiore P, Marigo M, Carlone A, Bartoli G. Angew. Chem. Int. Ed. 2008; 47: 6138
• 11e Yu X, Wang W. Chem. Asian J. 2008; 3: 516
• 11f Bertelsen S, Jorgensen KA. Chem. Soc. Rev. 2009; 38: 2178
• 11g Pihko PM, Majander I, Erkkila A. Top. Curr. Chem. 2010; 291: 29
• 11h Wende RC, Schreiner PR. Green Chem. 2012; 14: 1821
• 11i Hernández JG, Juaristi E. Chem. Commun. 2012; 48: 5396
• 12a Groselj U, Ricko S, Steve J, Stanovnik B. Chirality 2012; 24: 412
• 12b Reddy RJ, Lee P.-H, Magar DR, Chen J.-H, Chen K. Eur. J. Org. Chem. 2012; 353
• 12c Zhou Y, Liu Q, Gong Y. Org. Biomol. Chem. 2012; 10: 7618
• 12d Weng J, Ai H.-B, Luo R.-S, Lu G. Chirality 2012; 24: 271
• 12e Anwar S, Lee P.-H, Chou T.-Y, Chang C, Chen K. Tetrahedron 2011; 67: 1171
• 13 Siyutkin DE, Kucherenko AS, Frolova LL, Kuchin AV, Zlotin SG. Tetrahedron: Asymmetry 2011; 22: 1320

See, for example:
• 14a Juaristi E, Soloshonok VA. Enantioselective Synthesis of β-Amino Acids . 2nd ed. Wiley; Hoboken: 2005
• 14b Fülöp F, Martinek TA, Tóth G. Chem. Soc. Rev. 2006; 35: 323
• 15a Szakonyi Z, Martinek TA, Sillanpää R, Fülöp F. Tetrahedron: Asymmetry 2007; 18: 2442
• 15b Gyónfalvi S, Szakonyi Z, Fülöp F. Tetrahedron: Asymmetry 2003; 14: 3965
• 15c Koneva EA, Volcho KP, Gatilov YV, Koechagina DV, Salnikov GE, Salakhutdinov NF. Helv. Chim. Acta 2008; 91: 1849
• 15d Szakonyi Z, Martinek TA, Sillanpaa R, Fülöp F. Tetrahedron: Asymmetry 2008; 19: 2296
• 15e Szakonyi Z, Balázs A, Martinek TA, Fülöp F. Tetrahedron: Asymmetry 2010; 21: 2498
• 15f Szakonyi Z, Fülöp F. Amino Acids 2011; 41: 597
• 15g Szakonyi Z, Martinek T, Hetényi A, Fülöp F. Tetrahedron: Asymmetry 2000; 11: 4571
• 16 Wittenberger SJ, McLaughlin MA. Tetrahedron Lett. 1999; 40: 7175
• 17 Li J, Sha Y. Molecules 2008; 13: 1111

For examples of ¹H NMR DMSO-d ₆ titration experiments, see:
• 18a Luppi G, Lanci D, Trigari V, Garavelli M, Garelli A, Tomasini C. J. Org. Chem. 2003; 68: 1982
• 18b Vasbinder MM, Jarvo ER, Miller SJ. Angew. Chem. Int. Ed. 2001; 40: 2824
• 18c Fischer L, Didierjean C, Jolibois F, Semetey V, Lozano JM, Briand J.-P, Marraud M, Poteau R, Guichard G. Org. Biomol. Chem. 2008; 6: 2596
• 18d Copeland GT, Jarvo ER, Miller SJ. J. Org. Chem. 1998; 63: 6784
• 19a Lu L, An X, Chen J, Xiao W. Synlett 2012; 23: 490
• 19b Dahlin N, Bøgevig A, Adolfsson H. Adv. Synth. Catal. 2004; 346: 1101
• 19c Gintautas B, Haukka M, Butkus E. Synth. Commun. 2011; 41: 2517
• 19d Vázquez N, Gómez-Vallejo V, Calvo J, Padro D, Llop J. Tetrahedron Lett. 2011; 52: 615
• 19e Bagdžiūnas G, Haukka M, Butkus E. Synth. Commun. 2011; 41: 2523
• 20a Greene TW, Wuts PG. Protective Groups in Organic Chemistry . 4th ed. John Wiley & Sons; New York: 2007
• 20b Llobet AI, Álvarez M, Albericio F. Chem. Rev. 2009; 109: 2455
• 21 Hibbs DE, Hursthouse MB, Jones IG, Jones W, Malik KM. A, North M. J. Org. Chem. 1998; 63: 1496
• 22 Muneyuki R, Yoshimura Y, Tori K, Terui Y, Shoolery JN. J. Org. Chem. 1988; 53: 358

See, for example:
• 23a Davie EA, Mennen SM, Xu Y, Miller SJ. Chem. Rev. 2007; 107: 5759
• 23b Wennemers H. Chem. Commun. 2011; 47: 12036

See, for example:
• 24a Hernández JG, Juaristi E. Tetrahedron 2011; 67: 6953
• 24b Juaristi E. J. Org. Chem. 2012; 77: 4861; and references cited therein
• 25 Szakonyi Z, Fülöp F. ARKIVOC 2003; (xiv): 225
• 26 Wolff H. Org. React. 1946; 3: 307