An Asymmetric Dehydrogenative Diels-Alder Reaction For The Synthesis Of Chiral Tetrahydrocarbazole

Tetrahydrocarbazole skeleton,widely found in natural products,is an important structural unit in organic synthesis.Meanwhile,carbazole and derivatives have attracted widespread attention due to the frequent occurrence of bioactive natural and non-natural products,as well as some organic functional materials.In order to promote synthesis of natural products and the development of medicine even the organic materials science,the design of novel skeletons and the improvement of these compounds are essential.Accordingly,new and efficient methodologies for the synthesis of optically active and highly substituted tetrahydrocarbazoles are still in great demand in the fields of organic and medicinal chemistry.Even though remarkable developments have been achieved over the past decades according to the examples illustrated above,currently asymmetric dehydrogenative Diels-Alder reactions for the construction of complex chiral structures including optical active tetrahydrocarbazoles have not been reported probably because of the incompatibility of the chiral catalyst in oxidative systems.We described the first asymmetric dehydrogenative Diels-Alder reaction between 2-methyl-3-arylmethylindoles and ?,?-unsaturated aldehydes to provide optically active tetrahydrocarbazoles bearing three continuous chiral centers.In this paper,the oxidative asymmetric Diels-Alder cycloaddition reaction was studied using trimethyl siliconsubstituted hydroxy diphenyl proline as the chiral catalyst and the 2-methyl-3-benzyl indole and cinnamaldehyde as the substrates.Additionally,the four reaction parameters were studied including solvent,catalyst,acid and additives.After screening,we found that the highest yield(74%),high enantioselectivity(99%ee)was obtained when the 4A molecular sieves were added using palladium acetate as the additive in the presence of benzoic acid.In terms of substrate suitability,when the substituted 2-methyl-3-benzyl fluorene and cinnamaldehyde derivatives have different electrical substituents attached to the aromatic ring,they all have good results,indicating that the reaction With a good range of substrate adaptation,in addition,the product configuration has been in-depth research.