Photocatalytic Iminyl Radical-Mediated Cyclization Cascade For Synthesis Of 1,2,3,4-tetrahydrophenanthrenes

Tetrahydrophenanthrene compounds are encountered in many significantly important pharmaceuticals,bioactive natural products,and building blocks in organic and diversity-oriented synthesis.Traditional methods for the synthesis of tetrahydrophenanthrene compounds are limited in powerful but harsh reaction conditions and poor selectivity including wave irradiation and stoichiometric amount of Lewis acids.Therefore,it is desirable to explore new and efficient synthetic methods.In recent years,visible light photoredox catalysis has attracted widespread attention from organic chemists due to its green and economic characteristics.This catalytic strategy provides a valuable synthetic tool for the generation of iminyl radicals.In this context,cyclobutanone oxime ester derivatives,as precursors of iminyl radicals,have become a research top of increasing interest,because of their diverse reaction modes,and extensive application in the construction of cyanoalkylated compounds.This thesis focuses on the photocatalytic iminyl radical-mediated cyclization cascade for synthesis of 1,2,3,4-tetrahydrophenanthrenes,which not only enriches the chemistry of iminyl radicals,but also provides a new synthetic route for construction of tetrahydrophenanthrene skeleton.The details of this work are described as follows.We selected naphthyl-substituted cyclobutanone oxime esters as precursors of iminyl radical and electron-deficient olefins as radical acceptors.After screening of a series of conditions,we finally established that using fac-Ir(ppy)3 as the photocatalyst,Li2CO3 as the base,DMF as the solvent under the irradiation of 7 W blue LEDs,the reaction could give the best outcomes,and a series of functionalized tetrahydrophenanthrene compounds were synthesized with up to 89%yield under the optimal conditions.It is worth noting that the reaction could be scaled up to 1.0 mmol scale with comparable efficiency.When using sunlight instead of LED light source,we could also obtain the target product in 74%yield.In addition,on the basis of control experiments and free-radical trap experiments,the feature of photoredox catalysis and radical pathway were comfirmed.By using X-ray single crystal diffraction and DFT theoretical calculations,we verified and explained the unique selectivity of the strategy,and proposed a possible reaction mechanism.All of the target products were confirmed and fully characterized by 1H NMR,13C NMR and HRMS.This work has been published on Chemical Communication(2018,54,9925-9928)?...