Theoretical Study On The Mechanism Of Photoinduced Dearomatization Of Benzenoid Arenes

Dearomatization reaction is a kind of reaction that can directly convert aromatic hydrocarbons into aliphatic six-membered ring compounds.Many natural products and biologically active substances contain aliphatic six-membered ring compounds,and the construction of aliphatic six-membered ring structure is an important reaction.Although aromatic compounds are widely presented in nature,it is difficult for aromatic compounds to undergo dearomatization reaction due to their stable electronic structure.In organic synthesis,how to use aromatic hydrocarbons to construct aliphatic six-membered ring structures is a difficult problem.Therefore,it is meaningful to study the mechanism of dearomatization reaction for the development of dearomatization reaction.In 2016,Kutateladze et al.reported a very novel photoinduced dearomatization reaction,which is an intramolecular[4+2]cycloaddition process with high enantiomers of stereoselectivity.For example,the yield of the syn-product is 10%,the yield of the anti-product is 75%,therefore the anti-product is the main product.This reaction provides a fast and effective way to produce complex three-dimensional molecules.However,the mechanism and stereoselectivity of this reaction are unclear.In this paper,density functional theory（DFT）and time-dependent density functional theory（TDDFT）are used to study the mechanism and stereoselectivity of this photoinduced dearomatization reaction.The results show that the reaction is a stepwise[4+2]cycloaddition reaction with different states.First,the reactants are excited to S₂ state after FC excitation,and then transition to S₁ state through internal conversion（IC）at the intersection of S₂ and S₁,and then transition to T₁ state through intersystem crossing（ISC）at the intersection of S₁ and T₁.Excited state intramolecular proton transfer（ESIPT）occurs in the T₁ state,resulting in the formation of a reactive diradical intermediates.Starting from the reactive diradical intermediates,the following[4+2]reaction is divided into two steps:first step reaction occurs in T₁ state to form an N4-C5 bond to generation a five-membered ring intermediate,the second step reaction occurred in S₀ state,the formation of C1-C6bond generation product,the process involves the T₁ state to S₀ state intersystem crossing（ISC）process.The second step reaction is an unbarred process,so the first step is the rate-determining step of the dearomatization reaction.The stereoselectivity of enantiomers is mainly reflected in the benzyl hydroxyl group formed by T₁ state ESIPT rotates,the rotation is the syn-enantiomer,and the non-rotation is the anti-enantiomer.For the discussion of stereoselectivity,we use not only the recessive polarizable continuous solvent model（PCM）with dimethyl sulfoxide（DMSO）as the solvent choice,but also the explicit solvent model（PCM+DMSO）,in which the solvent and solute can interact through intermolecular hydrogen bonds.The results of the recessive model show that the energy barrier for the rotation of the benzyl hydroxyl group in the syn-path and the energy barrier for the formation of N4-C5 bonds is higher than the energy barrier for the formation of N4-C5 bonds in the anti-path.The reason is that the benzyl hydroxyl on ketone carbonyl methyl to the inside of the turn,causes steric hindrance to the formation of the N4-C5 bond,resulting in a higher energy barrier for the syn-path than the anti-path,and anti-path for the reaction of the main channel.The results of explicit solvation model indicate that the formation of DMSO with reactants can form effective intermolecular hydrogen bond（IHB）,which significantly reduces the energy barrier of the rotation of benzyl hydroxyl.But the energy barrier of the syn-path is still higher than that of the anti-path,and the anti-path is still the main pathway,which is consistent with the experimental results.In this paper,the mechanism of photoinduced dearomatization and the reason of stereoselectivity are explained reasonably.It is hoped that this reaction can be widely used in the synthesis of complex three-dimensional molecules and contribute to the development of dearomatization reactions.