文摘
A theoretical study of the intramolecular 5-exo-dig carbolithiation of substituted propargyl o-lithioaryl ethers, leading to dihydrobenzofurans, has been performed. The results show that a DFT description of the reaction (B3P86, 6-31G**) matches the experimental data provided that an explicit solvation by two molecules of THF is considered. To take place, the cyclization also implies that the acetylenic chain adopts a conformation in which a significant interaction arises between the lithium and the C鈮 triple bond. Reaching the cyclization TS requires the passage of an activation barrier that should not be higher than 12鈥?3 kcal mol鈥?. From a thermodynamic point of view, the reaction is exothermic whatever the substituent R (from approximately 鈭?0 to 鈭?2 kcal mol鈥?). In the starting substrate, a supplementary interaction between the Li and a substituent at the propargylic position can develop, influencing the future double-bond configuration. Thus, derivatives exhibiting an R鈥揕i interaction tend to provide E olefins. In contrast, when no coordination between the lithium cation and the terminal R occurs, syn carbolithiation takes place, and the configuration of the exocyclic olefin is likely to be Z. This hypothesis accounts for most of the experimental results published before.