C-H/C-D Exchange Reactions of Aromatic Compounds in D₂O with NaBD₄-Activated Catalysts

Abstract

A safe and efficient method for catalytic H/D exchange to provide high deuterium incorporation into a variety of aromatic substrates was developed. Systematic screening of the catalyst and activator revealed that the essential activation of the Pd or Rh ­catalyst could be achieved under safe and user friendly conditions. The application of this simple catalytic method for the deuteration of bi- and tricyclic aromatic compounds and chiral natural products was investigated.

Key words

deuterium - palladium - rhodium - heterogenous catalysis - alkaloids

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14

The formation of gaseous hydrogen after addition of NaBH₄ to an aqueous solution may be a basic principle, however, only solids were handled and the reaction vessel was closed not until bubbling had stopped.

15

We found a strong influence of the reactivity and type of Pd catalyst to the level of deuterium incorporation and therefore all reactions were performed with Pd/C (10% Pd) K-02105 purchased from Heraeus.

18

Typical Reaction Conditions.
Into a sealed tube under argon was given 1.00 mmol organic compound, 10 weight% catalyst, 5 mol% NaBD₄ (98% D) and 3 mL D₂O (99% D). The mixture was stirred for approximately 30 s and the tube was sealed (remark: the reaction vessel was closed not until bubbling had stopped) and heated to 130 °C for 18 h. The mixture was cooled to r.t. and 3 mL MeCN were added. The catalyst was separated by filtration. The product was purified by chromatography if necessary and analyzed by NMR and LC-MS.

19

The percentage of deuterium incorporation at every carbon was determined by ¹H NMR and ²H NMR experiments on a Bruker 500 spectrometer with anisic acid as internal standard. M_max was determined by an Agilent 1100 System LC-MS instrument.