A Palladium-Catalyzed Domino Reaction as Key Step for the Synthesis of Functionalized Aromatic Amino Acids

Abstract

A variety of substituted aromatic systems are synthesized by the Catellani reaction. These are used as precursors for novel amino acids with a basic side chain.

Key words

C–H activation - artificial amino acids - asymmetric synthesis - norbornene - Catellani reaction

• References and Notes

• 1a Krebs A, Ludwig V, Boden O, Göbel MW. ChemBioChem 2003; 4: 972
• 1b Ludwig V, Krebs A, Stoll M, Dietrich U, Ferner J, Schwalbe H, Scheffer U, Dürner G, Göbel MW. ChemBioChem 2007; 8: 1850
• 1c Ferner J, Suhartono M, Breitung S, Jonker HR. A, Hennig M, Wöhnert J, Göbel M, Schwalbe H. ChemBioChem 2009; 10: 1490
• 2a Krebs A, Ludwig V, Pfizer J, Dürner G, Göbel MW. Chem. Eur. J. 2004; 10: 544
• 2b Suhartono M, Weidlich M, Stein T, Karas M, Dürner G, Göbel MW. Eur. J. Org. Chem. 2008; 1608
• 2c Suhartono M, Schneider AE, Dürner G, Göbel MW. Synthesis 2010; 293

For recent reviews, see:
• 3a Chen DY.-K, Youn SW. Chem. Eur. J. 2012; 18: 9452
• 3b White MC. Synlett 2012; 2746
• 3c Wencel-Delord J, Dröge T, Liu F, Glorius F. Chem. Soc. Rev. 2011; 40: 4740
• 3d Gutekunst WR, Baran PS. Chem. Soc. Rev. 2011; 40: 1976
• 3e Ackermann L, Kapeli AR, Potukuchi HK, Kozhushkov SI In Handbook of Green Chemistry . Li C.-J. Wiley-VCH; Weinheim: 2012: 259-395
• 4a Catellani M, Frignani F, Rangoni A. Angew. Chem., Int. Ed. Engl. 1997; 36: 119
• 4b Catellani M, Cugini F. Tetrahedron 1999; 55: 6595

For an overview, see:
• 5a Ferraccioli R. Synthesis 2013; 581
• 5b Martins A, Mariampillai B, Lautens M. Top. Curr. Chem. 2010; 292: 1
• 5c Catellani M, Motti E, Della Ca’ N. Acc. Chem. Res. 2008; 41: 1512

For selected examples, see:
• 5d Weinstabl H, Suhartono M, Qureshi Z, Lautens M. Angew. Chem. Int. Ed. 2013; 52: 5305
• 5e Candito DA, Lautens M. Org. Lett. 2010; 12: 3312
• 5f Thansandote P, Chong E, Feldmann K.-O, Lautens M. J. Org. Chem. 2010; 75: 3495
• 5g Candito DA, Lautens M. Angew. Chem. Int. Ed. 2009; 48: 6713
• 5h Mariampillai B, Alliot J, Li M, Lautens M. J. Am. Chem. Soc. 2007; 129: 15372
• 5i Jafarpour F, Jalalimanesh N. Tetrahedron 2012; 68: 10286
• 6 Bonnaventure I, Charette AB. J. Org. Chem. 2008; 73: 6330
• 7 Mitsudo K, Thansandote P, Wilhelm T, Mariampillai B, Lautens M. Org. Lett. 2006; 8: 3939
• 8 Coleman RS, Mortensen MA. Tetrahedron Lett. 2003; 44: 1215
• 9 Blanchot M, Candito DA, Larnaud F, Lautens M. Org. Lett. 2011; 13: 1486
• 10 Catellani Reaction; General Procedure: Pd(OAc)₂ (45 mg, 0.2 mmol) and Ph₃P (115 mg, 0.44 mmol) were placed into an oven-dried sealable tube and dissolved in anhydrous MeCN (12 mL) under an argon atmosphere. After 5 min, Cs₂CO₃ (3.26 g, 10 mmol), the aryl iodide or triflate 1g (2 mmol), 1,3-dibromopropane (2.04 mL, 20 mmol; for iodobenzene (1a): 2.24 mL, 22 mmol) and methyl acrylate (906 μL, 10 mmol) were added. The reaction mixture was purged with argon for 5 min. After addition of norbornene (942 mg, 10 mmol), the tube was sealed and heated at 90 °C for 18 h. For workup, the cooled reaction mixture was filtered over Celite, washed with CH₂Cl₂, concentrated in vacuo and purified by column chromatography. Methyl (2E)-3-[2,6-Bis(3-bromopropyl)phenyl]prop-2-enoate (2a): Yield: 544 mg (67%); yellow oil. ¹H NMR (250 MHz, CDCl₃): δ = 7.87 (d, J = 16.3 Hz, 1 H, Ar-CH=CH), 7.21 (m, 1 H, Ar-H), 7.12 (m, 2 H, Ar-H), 6.03 (d, J = 16.3 Hz, 1 H, Ar-CH=CH), 3.83 (s, 3 H, COOCH₃), 3.38 (t, J = 6.5 Hz, 4 H, CH₂Br), 2.79 (t, J = 7.3 Hz, 4 H, CH ₂CH₂CH₂Br), 2.07 (m, 4 H, CH ₂CH₂Br). ¹³C NMR (63 MHz, CDCl₃): δ = 166.5, 143.2, 139.0, 134.2, 128.4, 127.7, 124.8, 51.8, 33.6, 33.0, 32.0. IR (neat): 2949 (m), 1722 (s), 1641 (m), 1576 (w), 1456 (m), 1434 (m), 1309 (m), 1272 (m), 1195 (m), 1169 (s), 1038 (w), 984 (m), 866 (w), 793 (w), 764 (m). R_f = 0.70 (n-hexane–EtOAc, 3:1). HRMS (MALDI): m/z [M + H]⁺ calcd for C₁₆H₂₁Br₂O₂: 402.9903; found: 402.9900. Methyl (2E)-3-[2-(3-Bromopropyl)pyren-1-yl]prop-2-enoate (2i): Yield: 562 mg (69%); yellow solid; mp 121–124 °C; R_f = 0.60 (n-hexane–EtOAc, 3:1). ¹H NMR (250 MHz, CDCl₃): δ = 8.43 (d, J = 16.3 Hz, 1 H, Ar-CH=CH), 8.33 (d, J = 9.5 Hz, 1 H, Ar-H), 8.18 (d, J = 7.5 Hz, 2 H, Ar-H), 8.10–7.97 (m, 5 H, Ar-H), 6.38 (d, J = 16.3 Hz, 1 H, Ar-CH=CH), 3.93 (s, 3 H, COOCH₃), 3.48 (t, J = 6.5 Hz, 2 H, CH₂Br), 3.25 (t, J = 7.3 Hz, 2 H, CH ₂CH₂CH₂Br), 2.31 (m, 2 H, CH ₂CH₂Br). ¹³C NMR (63 MHz, CDCl₃): δ = 166.8, 142.8, 136.6, 131.4, 131.1, 130.5, 129.5, 129.2, 128.3, 128.2, 127.0, 126.3, 126.0, 125.8, 125.6, 125.3, 124.6, 124.4, 123.7, 51.9, 34.0, 33.0, 32.6. IR (KBr): 2927 (m), 2857 (w), 1721 (s), 1638 (m), 1596 (w), 1437 (m), 1285 (s), 1200 (m), 1171 (s), 988 (m), 884 (m), 842 (s), 763 (m), 713 (m), 671 (w), 604 (w). Anal. Calcd for C₂₃H₁₉BrO₂: C, 67.82; H, 4.70. Found: C, 67.56; H, 4.76. See the Supporting Information for details of the other compounds.
• 11 Evans DA, Britton TC, Ellman JA, Dorow RL. J. Am. Chem. Soc. 1990; 112: 4011
• 12 Evans DA, Britton TC. J. Am. Chem. Soc. 1987; 109: 6881
• 13 See the Supporting Information for further details.
• 14 Höfler C, Rüchardt C. Liebigs Ann. 1996; 188
• 15 Basallote MG, Besora M, Castillo CE, Fernández-Trujillo MJ, Lledόs A, Maseras F, Máñez MA. J. Am. Chem. Soc. 2007; 129: 6608
• 16a Malacria M, Maestri G. J. Org. Chem. 2013; 78: 1323
• 16b Amatore C, Catellani M, Deledda S, Jutand A, Motti E. Organometallics 2008; 27: 4549
• 17a Cárdenas DJ, Martín-Matute B, Echavarren AM. J. Am. Chem. Soc. 2006; 128: 5033
• 17b Maestri G, Motti E, Della Ca’ N, Malacria M, Derat E, Catellani M. J. Am. Chem. Soc. 2011; 133: 8574