Iridium-Catalyzed Decarboxylative N-Alkylation of α-Amino Acids with Primary Alcohols

Abstract

A new decarboxylative N-alkylation reaction of α-amino acids has been developed. A variety of tertiary amines were obtained in good to excellent yields via the decarboxylative N-alkylation reaction of α-amino acids with primary alcohols catalyzed by a Cp*Ir complex.

Key words

iridium - amine - decarboxylative N-alkylation - amino acid - alcohol

• References and Notes

• 1a Salvatore RN, Yoon CH, Jung KW. Tetrahedron 2001; 57: 7785 ; and references cited therein
• 1b Chiappe C, Pieraccini D. Green Chem. 2003; 5: 193 ; and references cited therein

For reviews, see:
• 2a Suzuki T. Chem. Rev. 2011; 111: 1825
• 2b Guillena G, Ramón DJ, Yus M. Chem. Rev. 2010; 110: 1611
• 2c Dobereiner GE, Crabtree RH. Chem. Rev. 2010; 110: 681
• 2d Nixon TD, Whittlesey MK, Williams MJ. Dalton Trans. 2009; 753
• 3a Zheng L, Yang F, Dang Q, Bai X. Org. Lett. 2008; 10: 889
• 3b Bi H.-P, Teng Q, Guan M, Chen W.-W, Liang Y.-M, Yao X, Li C.-J. J. Org. Chem. 2010; 75: 783
• 3c Zhang C, Seidel D. J. Am. Chem. Soc. 2010; 132: 1798
• 3d Das D, Richers MT, Ma L, Seidel D. Org. Lett. 2011; 13: 6584
• 3e Zhang C, Das D, Seidel D. Chem. Sci. 2011; 2: 233
• 3f Wang Q, Wan C, Gu Y, Zhang J, Gao L, Wang Z. Green Chem. 2011; 13: 578
• 3g Wang Q, Zhang S, Guo F, Zhang B, Hu P, Wang Z. J. Org. Chem. 2012; 77: 11161
• 4a Coldham I, Hufton R. Chem. Rev. 2005; 105: 2765
• 4b Pandey G, Banerjee P, Gadre SR. Chem. Rev. 2006; 106: 4484
• 5 Wu J, Wang F, Ma Y, Cui X, Cun L, Zhu J, Deng J, Yu B. Chem. Commun. 2006; 1766
• 6 General Procedure for the Preparation of 3 To a solution of [Cp*IrCl₂]₂ (0.0025 mmol), amino acid 2 (0.65 mmol), and NaHCO₃ (0.05 mmol) in toluene (3 mL) under an atmosphere of argon was added alcohol 1 (0.5 mmol). The resulting mixture was stirred at 110 °C for a certain period of time. The reaction mixture was cooled to r.t., and H₂O (5 mL) was then added. The resulting solution was extracted with EtOAc. Purification on silicon gel afforded the desired products 3. General Procedure for the Preparation of 4 To a solution of [Cp*IrCl₂]₂ (0.0075 mmol), glycine (2c, 0.5 mmol), and KOH (0.15 mmol) in toluene (3 mL) under an atmosphere of argon was added alcohol 1 (1.0 mmol). The resulting mixture was stirred at 110 °C for a certain period of time. The reaction mixture was cooled to r.t., and H₂O (5 mL) was then added. The resulting solution was extracted with EtOAc. Purification on silicon gel afforded the desired products 4. Data of Unknown Compounds Compound 3n: yellow oil. IR: 3063, 3032, 2961, 2784, 1606, 1589, 1510, 1455, 1378, 1265, 1227, 1163, 1136, 1023, 853, 809, 736 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.49–7.40 (m, 4 H), 7.39–7.32 (m, 4 H), 7.32–7.27 (m, 2 H), 7.00 (d, J = 1.8 Hz, 1 H), 6.87 (d, J = 8.1 Hz, 1 H), 6.82 (dd, J = 8.2, 1.9 Hz, 1 H), 5.17 (s, 2 H), 5.14 (s, 2 H), 3.58 (s, 2 H), 2.58–2.46 (m, 4 H), 1.84–1.72 (m, 4 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 148.7, 148.3, 137.4, 137.3, 131.3, 128.5, 128.4, 127.8, 127.7, 127.4, 127.3, 122.2, 116.2, 114.8, 71.4, 71.2, 59.7, 53.6, 23.3 ppm. ESI-HRMS: m/z calcd for C₂₅H₂₇NO₂ [M + H]: 374.2115; found: 374.2117. Compound 3o: yellow oil. IR: 3064, 3034, 2961, 2789, 1602, 1588, 1495, 1453, 1376, 1348, 1241, 1123, 1050, 1024, 880, 858, 754, 697 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.42 (m, 3 H), 7.41–7.37 (m, 2 H), 7.36–7.31 (m, 1 H), 7.24 (dt, J = 8.2, 2.1 Hz, 1 H), 6.93–6.99 (m, 2 H), 5.09 (s, 2 H), 3.91 (s, 2 H), 2.74–2.78 (m, 4 H), 1.85–1.80 (m, 4 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 156.8, 137.1, 131.5, 128.9, 128.6, 127.9, 127.3, 125.1, 120.9, 111.9, 53.2, 52.5, 23.3 ppm. ESI-HRMS: m/z calcd for C₁₈H₂₁NO [M + H]: 268.1696; found: 268.1695.