Catalytic Method of Deuterium Gas Generation Using D_2O and Pd/C and Its Application to Synthesis of Deuterium-Labeled Compound

本文报道了Pd/C催化的D_2O和H_2之间的H_2-D_2交换反应及其在制备氚标记化合物中的应用。密封在反应瓶中的H_2被有效地转化为纯D_2，可用于各种可还原官能团的一锅还原氢化。此外，在保留其他各种可还原官能团的情况下，通过加入微量的Ph_2S完成了烯烃和乙炔的化学选择性氢化反应。还提出了一种捕集产生的D2气体的方法。H_2-D_2交换反应的显著特点是高效、廉价、环保和方便。此外，在没有昂贵的D_2气体的情况下，以非均相Pd/C为催化剂，开发了一种简单、温和和区域选择性的苄基位置的H-D交换反应。该方法可以得到具有良好的氚效率的相应的氚标记化合物。在含有少量氢气的条件下，使用10%的Pd/C在室温下以较便宜的D-2O作为氢源进行氢-氢交换72h，并且在温和加热(50℃)的条件下反应速度显著加快，从而缩短了反应时间，扩大了底物的适用范围。对于在Pd/C催化加氢条件下一般不稳定的苯基醚，也可以进行H-D交换反应，以Pd/C(En)代替Pd/C，具有较高的氢效率。此外，使用D2O和D2O混合(7：3)的溶剂成功地抑制了相应的苄基醚的氢解。本方法对于简化复杂的~1H核磁共振图谱也是非常有用的。这些方法的普遍实用性将使这种简单的技术成为一种有吸引力的广泛的氢化程序的补充。

The Pd/C-catalyzed H_2-D_2 exchange reaction between D_2O and H_2 and its application to the preparation of deuterium labeled compounds have been demonstrated. H_2 sealed in the reaction flask was efficiently converted into pure D_2, which can be used for the one-pot reductive deuteration of a variety of reducible functionalities. Furthermore, the chemoselective deuterogenation of olefins and acetylenes was accomplished by the addition of a trace amount of Ph_2S with retention of the various other reducible functionalities. A method of capturing the generated D_2 gas was also developed. The significant features of the H_2-D_2 exchange reaction are efficiency, inexpensiveness, environmental-friendly and convenience. Furthermore, a simple, mild, and regioselective H-D exchange reaction at the benzylic sites using the heterogeneous Pd/C as a catalyst without expensive D_2 gas was developed. The present method can afford the corresponding deuterium-labelled compounds with excellent deuterium efficiency. The use of 10% Pd/C in the presence of a small amount of hydrogen gas could achieve an efficient H-D exchange using the less expensive D-2O as the deuterium source at room temperature for 72 h. Furthermore, this reaction is dramatically accelerated under mild heating (50℃) conditions, resulting in shortening the reaction time and expanding the applicability of the substrates. The H-D exchange reaction could also be used for the deuteration of benzyl ethers, which were generally unstable under Pd/C-catalyzed hydrogenation conditions, with a high deuterium efficiency using Pd/C(en) instead of Pd/C. Furthermore, the use of THE and D_2O mixed (7:3) solvent successfully suppressed the hydrogenolysis of the corresponding benzyl ether. The present method would also be very useful for the simplification of complex ^1H NMR charts.The general utility of these methodologies will make such simple techniques an attractive addition to the wide range of deuteration procedures.