One‐Pot and Two‐Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D‐Labeled Derivatives
Maria S. Ledovskaya, Mikhail V. Polynski, Valentine P. Ananikov
Abstract
Abstract Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6‐disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C 2 unit installation procedures in a common reaction space mode ( one‐pot ) and distributed reaction space mode (two‐chamber): (1) an interaction of 1,2,4,5‐tetrazine and its acceptor‐functionalized derivatives with a CaC 2 −H 2 O mixture performed in a two‐chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5‐tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D 2 O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5‐dideuteropyridazines of 95–99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.