Continuous Flow Optimisation of the Pudovik Reaction and Phospha-Brook Rearrangement Using DBN

Flow chemistry has shown significant versatility over the last two decades, offering advantages in efficiency, scalability, and sustainability. In this study, the continuous stirred tank reactor (CSTR) was used to optimise the synthesis of alpha-hydroxyphosphonates via the Pudovik reaction and their subsequent conversion to phosphates through the phospha-Brook rearrangement. The study highlights that using CSTRs allows for better control over reaction parameters, leading to reduced reaction times and improved yields compared to traditional batch methods. The optimised conditions successfully facilitated a range of organophosphates, including electron-rich and electron-poor derivatives, with high efficiency. Additionally, a one-pot tandem process combining the Pudovik reaction and the phospha-Brook rearrangement was developed, reducing reaction times to two hours while maintaining comparable yields. This work demonstrates the potential of CSTRs in flow chemistry for synthesising complex organophosphorus compounds, achieving higher reaction yields and shorter reaction times, highlighting the effectiveness of continuous flow methodologies.