The Synthesis Of Heteroatom-Substituted Gem-Diarylmethyl Compounds

Heteroatom-substituted gem-diarylmethyl compounds are widely present in natural products and pharmaceutical molecules.These compounds are also very important in the field of materials,and can also be used as intermediates in organic synthesis reactions,so they have important synthetic value.Recently,p-QMs?Para-Quinone methides?is a hot spot in organic chemistry field.As a good reactive intermediate,1,6-conjugated addition mainly occurs due to its special structure of amphoteric resonance.Therefore,based on this special property of p-QMs,we can effectively construct C-P,C-N and C-S bonds,there by synthesizing heteroatom-substituted gem-diarylmethyl compounds.In the first part of this research,the research on the reactivity of p-QMs and the pre-synthesis of p-QMs,acid-catalyzed in-situ generation-related reactions and base-catalyzed in-situ generation-related reactions were reviewed.Secondly,the research progress on the synthesis of gem-diarylmethyl phosphates,gem-diarylmethylamines,and gem-diarylmethyl sulfones is reviewed.The second part of this study was designed to realize the synthesis of gem-diaryl methyl phosphates.Traditional methods include Michaelis–Arbuzov reaction,Friedel–Crafts reaction,metal catalysis method,1,6-conjugated addition of pre-synthesis p-QMs compounds,and aromatic nucleophilic substituted reaction.The use of these methods inevitably has the disadvantages of high toxicity,limited substrate range,complex catalyst preparation,and low atom economics.Therefore,we used TBAB to catalyze the1,6-conjugated addition reaction of phosphites under the conditions that p-QMs intermediates were generated in situ by the base stimulate gem-diarylmethylsulfone compounds decomposition,and construct gem-diarylmethyl phosphate ester compounds.It was found that under the effect of 20 mol%catalyst loading TBAB,the addition of 1.2equivalents of Cs₂CO₃ gave the best reaction at 55°C in DMSO solvent.50 compounds were synthesized with a reaction yield of 44%-97%.The rate is good.It can tolerate various substituent groups,and has achieved good yields for benzene electron-withdrawing and electron-donating substituents,and the replacement of phenolic hydroxyl ortho-disubstituted groups also has good yields,achieving this type of compound Efficient synthesis.At the same time,we performed X-ray diffraction analysis on the products,and derivatized and transformed the products,expanding its application value.The third part of this paper is designed to realize the synthesis of gem-diarylmethyl amine derivatives.Traditional methods mainly focus on the metal catalysis reduction and addition of imines.The use of these methods inevitably has the disadvantages of requiring a large number of additives,dangerous gases,and expensive catalysts.p-QMs is a good addition reaction receptor,but there are few studies on 1,6-conjugated addition reaction of p-QMs with amines.Recently reported Ortho-Quinone methides in situ generation Addition with ammonia in water,but the reaction time is long and the atom economy is low.Therefore,we have efficiently synthesized gem-diarylmethyl amines through 1,6-conjugated addition reaction of the pre-synthesized p-QMs with amines under the catalysis of bases.It was found that DBU catalyzed the reaction with an optimal catalyst loading of 20 mol%in acetonitrile solution to obtain the best results.Twelve such compounds were synthesized with a reaction yield of 45%-97%and good yields,suitable for a variety of amines Compound.We applied it to addition of piperazine compounds and also achieved good yields.The fourth part of this paper is designed to realize the green synthesis of gem-diarylmethyl sulfone compounds.Traditional synthesis methods include acid-catalyzed hydroxyl conversion,metal catalysis,and reactions in ionic liquids.However,these methods inevitably have disadvantages such as large substrate limitation,high reagent toxicity,and complicated substrate preparation.The sources of sulfone functional groups are mainly divided into three compounds:sodium p-toluene sulfinate,p-toluenesulfonyl hydrazide,and p-toluenesulfonyl methyl isocyanate.Therefore,according to reports in the literature,we speculate that sulfonyl hydrazide can be thermally decomposed in aqueous solution and catalyze the in situ formation of p-QMs intermediate from gem-diarylmethyl alcohol and occur 1,6-conjugated addtion reaction.A gem-diarylmethyl sulfone compound was synthesized.We found that the best effect was achieved by heating to 60°C for 9 hours in the aqueous phase.This compound was constructed with a rgood yield,and no need for additional catalysts.And additives.In this paper,p-QMs?Para-Quinone methides?,a special structure of organic synthesis reaction intermediate,was used to construct the C-P,C-N and C-S bonds through 1,6-conjugated addition reaction,and the heteroatom-substituted gem-diarylmethyl compounds was successfully realized.The method developed in this paper provides an efficient and convenient synthetic route for such compounds.