Theoretical study on the mechanism of the synthesis reaction of chroman derivatives

Abstract

We have been investigating this concept, called In Silico screaning of synthesis routes, by combining theoretical calculations and chemoinformatics. A mitsunobu reaction, one of the synthesis routes for 2,6-dimethylchroman-4-one 1, which the KOSP program created, was examined using the DFT calculations at the B3LYP/6-31+G level of theory. We found a transition state structure which leads to the key intermediate of Mitsunobu reaction from a phenolate derivative ion. Another TS for the side product was also found although the energy difference between the two TSs is higher than that expected from the experimental result. These mechanisms are consistent with results from synthesis experiments.