Copper/Chiral Phosphoric Acid Catalyzed Desymmetrization Of Diene For Preparing Chiral Vicinal Diamines

Chiral vicinal diamines widely exist in many natural products,drug molecules,chiral ligands and asymmetric organocatalysts.Thus,tremendous attention has been attracted from chemists to develop efficient methods for synthesizing this kind of functional groups.The amines used in the traditional asymmetric diamination of alkenes need to be protected by electron-withdrawing groups,while the most common alkyl amines are rarely used as amine sources.This is mainly due to the Lewis basicity and oxidizability of alkyl amines.The addition of nitrogen-centered radicals to alkenes can be used to construct the C-N bond,providing a series of amination reactions.However,there have been few reports about the asymmetric attack of nitrogen-centered free radicals on alkenes,which is very challenging.All cases reported so far are based on nitrogen-centered radicals protected by electron-withdrawing groups.Compared with these electron-deficient nitrogen-centered radicals,alkylaminyl radicals have many disadvantages such as poor stability,high tendency towards side reactions and slow rate of attack on alkenes.Therefore,the realization of asymmetric attack of common alkylaminyl radicals on alkenes constitutes a great challenge but is highly desirable.Our research group has recently achieved the asymmetric diamination of alkenes using the strategy of attacking alkenes with alkylaminyl radicals,but the construction of chiral carbon centers was not involved in the step of radical attack.On this basis,effective stereocontrol over the attack of alkylaminyl radicals on olefins was proposed for enantioselective desymmetrization of symmetrical dienes.Through investigations on reaction conditions with different chiral phosphoric acids,copper salts,solvents and additives,the optimized conditions were identified.Thus,the in-situ generated dialkylaminyl radicals successfully attacked dienes asymmetrically in the presence of copper/chiral phosphoric acid.And the asymmetric diamination of alkenes was achieved with high enantioselectivity and diastereoselectivity.The reaction exhibited excellent functional-group compatibility and featured a wide substrate scope,thus providing a very promising method for the efficient synthesis of drugs,natural products and chiral ligands containing chiral vicinal diamine motifs.Mechanistic studies on the reaction revealed a free radical pathway.Further transformation of one reaction product led to a natural alkaloid analogue,which has the potential to be used as chiral ligand.