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DOI: 10.1055/s-2004-830855
Selective N-Benzylation of Amino Acids under Homogeneously Catalyzed Hydrogenation Conditions
Publication History
Publication Date:
28 July 2004 (online)
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Abstract
The chemoselective N-benzylation of the α-amino acids l-proline, l-serine and l-threonine is described using a reductive amination procedure with benzaldehyde catalyzed by homogeneous Rh-complexes affording N-benzyl protected amino acids.
Key words
hydrogenation - transition metals - catalysis - amino acids
- 1
Coppola GM.Schuster HF. In Asymmmetric Synthesis: Construction of Chiral Molecules Using Amino Acids Wiley; New York: 1987. -
2a
Kocienski PJ. Protective Groups Thieme; Stuttgart: 1994. -
2b
Greene TW.Wuts PGM. Protective Groups in Organic Synthesis Wiley; New York: 1999. -
3a
Cain CM.Cousins RPC.Coumbarides G.Simpkins NS. Tetrahedron 1990, 46: 523 -
3b
Guy A.Barbetti JF. Synth. Commun. 1992, 22: 853 -
3c
Sclafani JA.Maranto MT.Sisk TM.Van Arman SA. J. Org. Chem. 1996, 61: 3221 - 4
Quitt P.Hellerbach J.Vogler K. Helv. Chim. Acta 1963, 46: 327 - 5
Belokon YN.Tararov VI.Maleev VI.Savel’eva TF.Ryzhov MG. Tetrahedron: Asymmetry 1998, 9: 4249 - 6 For hydrogenation conditions, see:
Tararov VI.Kadyrov R.Riermeier TH.Börner A. Adv. Synth. Catal. 2002, 344: 200 - 8
Brown GR.Foubister AJ.Wright B. J. Chem. Soc., Perkin Trans. 1 1985, 2577
References
(
S
)-
N
-Benzylproline. In a typical run, a 50-mL Parr autoclave was charged with 32 mg (0.0345 mmol) of commercial (Ph3P)3RhCl complex. Air was evacuated by three vacuum-Ar cycles. A solution of 4.00 g (34.7 mmol) of (S)-Pro in 30.0 mL MeOH (prepared in an Ar atmosphere) was introduced into the autoclave with a needle followed by addition of 5.3 mL (5.57 g, 52.4 mmol) of PhCHO. The autoclave was pressurized with 50 bar of H2. The reaction mixture was stirred at r.t. for 3 d until uptake of H2 ceased. The autoclave was opened and the resulted solution evaporated. The residue was triturated under acetone and the solid was filtered and washed twice with acetone. The product was dried on air. Mp 178-179 °C (Lit.5 mp 174-175 °C). [α]D
24 = -27.9 (c 1 in EtOH) [Lit.5 [α]D
20 = -25.8 (c 1 in EtOH)]. Anal. Calcd for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.12; H, 7.34; N, 6.79. 1H NMR (CD3OD-CDCl3): δ = 1.89-2.12 (m, 2 H), 2.13-2.28 (m, 1 H), 2.33-2.49 (m, 1 H), 3.57-3.69 (m, 1 H), 3.89 (dd, 1 H, J = 9.1, 6.6 Hz, α-CH), 4.26 (d, 1 H, J = 12.8 Hz, CH
a
HbPh), 4.45 (d, 1 H, J = 12.8 Hz, CHa
H
b
Ph), 7.38-7.54 (m, 5 H, ArH).
(
S
)-
N
-Benzylserine. Mp 214-216 °C (decomp.) (Lit.8 mp 235-236 °C). [α]D
24 = 5.6 (c 1 in 6 N HCl)[Lit.8 S-isomer [α]D
22 = 4.9 (c 1 in 6 N HCl), R-isomer [α]D
22 = -5.5 (c 1 in 6 N HCl)]. Anal. Calcd for C10H13NO3: C, 61.53; H, 6.71; N, 7.18. Found: C, 61.42; H, 6.43; N, 7.16. 1H NMR (CD3OD-DCl conc.): δ = 4.05-4.26 (m, 3 H, α-H and β-H2-Ser), 4.38 (d, 1 H, J = 13.0 Hz, PhCH
a
Hb), 4.42 (d, 1 H, J = 13.0 Hz, PhCHa
H
b
), 7.44-7.52 (m, 3 H, ArH), 7.55-7.63 (m, 2 H, ArH). 13C NMR (CD3OD- DCl conc.): δ = 51.78 (CH2), 60.42 (CH2), 62.35 (CH), 131.04 (CH), 131.61 (CH), 132.08 (CH), 132.23 (C), 170.54 (COO).
(
S
)-
N
-Benzylthreonine. Mp 237-238 °C. [α]D
24 = -15.1 (c 1 in 6 N HCl). Anal. Calcd for C11H15NO3: C, 63.14; H, 7.23; N, 6.69. Found: C, 63.15; H, 7.07; N, 6.67. 1H NMR (CD3OD- DCl conc.): δ = 1.35 (d, 3 H, J = 6.5 Hz, Me), 3.72 (d, 1 H, J = 6.5 Hz, α-H), 4.24 (dq, 1 H, J = 6.5, 6.5 Hz, β-H), 4.36 (d, 1 H, J = 13.0 Hz, PhCH
a
Hb), 4.42 (d, 1 H, J = 13.0 Hz, PhCHa
H
b
), 7.44-7.52 (m, 3 H, ArH), 7.53-7.60 (m, 2 H, ArH). 13C NMR (CD3OD-DCl conc.): δ = 21.48 (CH3), 52.32 (CH2), 66.40 (CH), 67.50 (CH), 131.09 (CH), 131.74 (CH), 131.96 (C), 132.28 (CH), 170.40 (COO).