Efficient and Selective Deuteration of Phenylalanine Derivatives Catalyzed by Pd/C

Abstract

A facile and efficient deuteration method of phenylalanine derivatives using a Pd/C-H₂-D₂O system has been developed. Selective deuteration at the β-position of phenylalanine derivatives occurred using Pd/C as a catalyst with high deuterium efficiency without racemization at 110 °C. Also, the α-position was deuterated at higher temperature.

palladium - catalysis - amino acids - deuteration - regio­selectivity

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D₂ gas [$ 96.40/10 L of D₂ gas (Aldrich 36,186-0) in lecture bottle] is also purchased as a lecture bottle or cylinder charged by high-pressure.

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Typical Procedure for Selective Deuteration at the β-position of Phenylalanine Derivatives Using Pd/C-H ₂ -D ₂ O System and Selected Spectroscopic Data. [14]
A mixture of phenylalanine derivatives (0.5 mmol) and 10% Pd/C (Aldrich; 10 wt% of substrate) in D₂O (2 mL) was stirred under ordinary hydrogen pressure at 110 °C for 6 h. The reaction mixture was filtered through a membrane filter (Millepore, Millex^®-LH, 0.45 µm), and the filtrate was concentrated in vacuo. The residue was treated with H₂O to replace the deuterium on the heteroatoms (CO₂D and ND₂) with a hydrogen to afford the β-deuterated phenylalanine. Deuterium efficiency was determined by ¹H NMR using p-anisic acid sodium salt as an internal standard. l-Phenyl-alanine-β,β-d ₂: ¹H NMR (400 MHz, D₂O): δ = 2.94 (d, J = 8.3 Hz, 0.04 H), 3.11 (d, J = 5.1 Hz, 0.05 H), 3.82 (s, 1 H), 7.15-7.28 (m, 5 H). ²H NMR (60.7 MHz, H₂O): δ = 2.91, 3.08. MS (EI): m/z = 167 [M⁺].

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<A NAME="RU01405ST-12">12</A> We have recently reported that 10% Pd/C catalysts exhibit remarkable supplier-dependent difference in the property and quality (acidity). Merck’s catalyst is more acidic than Aldrich’s one, see: Iwaka T. Sajiki H. Hirota K. Tetrahedron  2004,  60:  6189 

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<A NAME="RU01405ST-14">14</A>

The reaction may be taken care of the internal pressure which rise up to about 2.5 atm in the sealed tube.