Synlett 2004(11): 1961-1962  
DOI: 10.1055/s-2004-830855
LETTER
© Georg Thieme Verlag Stuttgart · New York

Selective N-Benzylation of Amino Acids under Homogeneously Catalyzed Hydrogenation Conditions

Vitali I. Tararov*a, Renat Kadyrovb, Christine Fischera, Armin Börner*a,c
a Leibniz-Institut für Organische Katalyse, Universität Rostock e.V., Buchbinderstr. 5/6, 18055 Rostock, Germany
Fax: +49(381)4669324; e-Mail: vitali.tararov@ifok.uni-rostock.de; e-Mail: armin.boerner@chemie.uni-rostock.de;
b Degussa AG, Projekthaus Katalyse, Industriepark Höchst, G 830, 65926 Frankfurt/Main, Germany
c Fachbereich Chemie, Universität Rostock, A.-Einstein-Str. 3a, 18059 Rostock, Germany
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Publikationsverlauf

Received 12 May 2004
Publikationsdatum:
28. Juli 2004 (online)

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.

    References

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  • 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 
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  • 6 For hydrogenation conditions, see: Tararov VI. Kadyrov R. Riermeier TH. Börner A. Adv. Synth. Catal.  2002,  344:  200 
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7

( 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).