Studies On The Aminomethylamination Of O-Hydroxystyrenes With Aminals

Amine compounds are widely found in the human body,the natural world,animals and plants.As a very important diamines,the status of 1,3-diamine is undoubted.Currently there are few literatures related to the synthesis of 1,3-diamines,which can be divided into three major categories: Stoichiometric reactions,transition-metal catalyzed reactions and synthesis of chiral 1,3-diamines.In this paper,a very simple olefin(o-hydroxystyrene)was used as starting material to undergo an aminomethylamination reaction with our group's own unique compound aminals.This method to synthesis of 1,3-diamines was an atom economy 100% reaction.Through a series of screenings,we found that the reaction can be successfully carried out without adding any catalysts,ligands or additives and the yield is as high as 88%.Through the screening of temperature,time and solvent,we determined the optimal reaction conditions,methylene chloride is finally found the best solvent and the reaction best at room temperature for 12 hours.After the experimental conditions were confirmed,we first extended the substrate of the o-hydroxystyrene and found that both the electron-donating substituent and the electron-deficient substituent had good yields(The highest yield up to 93%).Then,we extended the substrate of the aminals.We found that when the aminal with an electron-withdrawing substituent on the benzyl group can achieve higher yields than an electron-donating substituent.In addition to the reaction of aromatic aminals,aliphatic aminals can also undergo aminomethylamination reactions.In order to further explore the reaction by grading experiments,we found that when the amount of o-hydroxystyrene was 24 mmol,the yield of the reaction could still reach to 87%.For the product 1,3-diamines,we also performed a series of transformation.First,the standard product 1,3-diamines,undergoes a nucleophilic substitution reaction with trifluoromethanesulfonate,followed by coupling with phenylboronic acid or alkyne.Under specific reaction conditions,o-hydroxystyrene can also react with aminals to synthesize chiral 1,3-diamines.This paper synthesizes chiral diamines in two ways.One is the regulation of chiral ligands,the other is induction of chiral substrates.The best chirality obtained by the laboratory's existing chiral ligands is 23% ee.From the known experimental results,the synthesis of chiral 1,3-diamine is feasible.The more excellent results need to be further explored.