Geometric constraints regulated regioselectivity: Pd-catalyzed α-deuteration of pyridines with secondary phosphine oxide.

A Pd-catalyzed regioselective H/D exchange at the α-position of pyridines was achieved by employing secondary phosphine oxide as an internal base. The proposed five-membered structure enabled the reaction to overcome its conventional ortho-directing feature, allowing the efficient deuteration of pyridines and quinolines at adjacent sites of N-atoms.

Pd-Catalyzed Regioselective Deuteration of Indole's C4-Position with Transient Directing Groups.

As a representative scaffold of alkaloids, indoles have been extensively subjected to deuteration, but the regioselective C4 labeling has not been achieved due to its low reactivity. In this work, a Pd-catalyzed deuterium labeling at the indole's C4 position has been developed under the strategy of transient directing, using D2O as a deuterium source. The substituent effect is found to be crucial in facilitating this H/D exchange process, where the reversing C-D bond formation favors an electron-enriched ligation contrary to its C-H halogenation counterpart.

Potassium tert-butoxide promoted regioselective deuteration of pyridines.

A regioselective deuteration at the ß- and γ-position of pyridines is reported. Efficient deuteration occurred with a combination of KOtBu and DMSO-d6, replenishing the prevailing α-deuteration of the pyridine systems. Preliminary mechanistic studies suggested that the dimsyl carbanion acts as one of the key intermediates.