Synlett 2003(12): 1898-1900
DOI: 10.1055/s-2003-41470
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of Arylalanines via Asymmetric aza-Darzens (ADZ) Reaction

Naomi E. Maguire, Andrew B. McLaren, J. B. Sweeney*
Department of Chemistry, University of Reading, Reading RG6 6AD, UK
Fax: +44(118)93786331; e-Mail: j.b.sweeney@reading.ac.uk;
Further Information

Publication History

Received 30 June 2003
Publication Date:
19 September 2003 (online)

Abstract

(R)-3-Arylalanines may be prepared in high enantio­meric purity from N-dpp imines by a four-step reaction sequence involving asymmetric aza-Darzens reaction, dephosphinylation, hydrogenolysis and hydrolysis. The amino acids thus obtained were of >95% enantiomeric purity.

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Representative Experimental Procedure: To cis-2S,2′S,3′S-N-[(3-(phenyl)-2-aziridinyl)carbonyl]bornane-10,2-sultam (4a) in a EtOAc:MeOH (1:1) mixture (5 mL) was added a substoichiometric amount of H2O, TFA and Pd(OH)2 (42 mg, 0.06 mmol). The flask was then pump filled with hydrogen and stirred at atmospheric pressure and r.t. overnight. After this time the solution was filtered through a pad of Celite®, the pad washed with further MeOH. The solvent was removed in vacuo to afford S-(5a) as a colourless solid (110 mg, 0.3 mmol, 99%); Rf = 0.46 (EtOAc); [α]D 20 +66.7 (c 1, CHCl3). IR (CCl4): νmax = 3019, 2951 (CH), 1672 (C=O), 1334, 1170 (SO2), 756, 721, 702 (Ar) cm-1. 1H NMR (250 MHz, CD3OD): δ = 1.05 and 1.20 (6 H, 2 × s), 1.28-1.50 and 1.88-2.15 (7 H, m), 2.89 (1 H, dd, J = 10.6 Hz, 14.5 Hz), 3.65 (1 H, dd, J = 2.8 Hz, 14.5 Hz), 3.76 and 3.87 (2 H, 2 × d, J = 14.2 Hz), 4.05 (1 H, dd, J = 5.0 Hz, 7.9 Hz), 4.61 (1 H, dd, J = 2.8 Hz, 10.6 Hz), 7.32-7.47 (5 H, m). 13C NMR (60 MHz, CD3OD): δ = 20.53, 21.60, 27.59, 33.95, 39.43, 37.90, 46.50, 49.70, 51.08, 53.72, 56.10, 67.26, 129.49, 130.70, 130.92, 135.92, 168.55. MS (CI): m/z (%) = 363 (33) [MH]+, 271 (22), 120 (100), 91 (13), 58 (4). Found: [MH]+, 363.1732, C19H27N2O3S requires [MH]+, 363.1743.