Deuteration Degree‐Controllable Methylation via a Cascade Assembly Strategy using Methylamine‐Water as Methyl Source

We present a novel and effective photocatalytic method for the methylation of β‐diketones with controllable degrees of deuterium incorporation via development of new methyl sources. By utilizing a methylamine‐water system as the methyl precursor and a cascade assembly strategy for deuteration degree control, we synthesized methylated compounds with varying degrees of deuterium incorporation, showcasing the versatility of this approach. We examined a range of β‐diketone substrates and synthesized key intermediates for drug and bioactive compounds with varying degrees of deuterium incorporation, ranging from 0 to 3. We also investigated and discussed the postulated reaction pathway. This work demonstrates the utility of readily available reagents, methylamines and water, as a new methyl source, and provides a simple and efficient strategy for the synthesis of degree‐controllable deuterium‐labelled compounds. Methylamine‐water system was developed as a new methyl source for the methylation of β‐diketones under mild photocatalytic reaction conditions. Degree‐controllable deuterated methylation could be easily achieved by using distinct combinations of d‐methylamine‐D2O system, allowing for the synthesis of deuterium‐labelled bioactive molecules with a controllable number ranging from 0 to 3.