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

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.

aziridine - dpp - hydrogenolysis - (R)-amino acid

References

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<A NAME="RG15203ST-6">6</A> The Dictionary of Organic Compounds   Vol. 5:  Chapman and Hall; London: 1996.  p.3126 

<A NAME="RG15203ST-7">7</A>

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%); R_f = 0.46 (EtOAc); [α]_D ²⁰ +66.7 (c 1, CHCl₃). IR (CCl₄): ν_max = 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.

<A NAME="RG15203ST-8">8</A> The Dictionary of Organic Compounds   Vol. 4:  Chapman and Hall; London: 1996.  p.3126