Synthesis Of Sulfone Compounds Based On C-N Bond Breaking Of Quaternary Ammonium Salt

There are abundant compounds containing C-N bonds in nature,and how to realize the transformation of inert C-N bonds is very challenging and significant.Therefore,based on the application of transition metals in the field of sulfur dioxide insertion reaction,we design and develop a new type of catalytic system,using quaternary ammonium salts containing active C-N bonds as electrophiles,a series of small sulfone molecules with pharmacological activity were synthesized through the cleavage of C-N bonds.In this paper,sodium arylsulfinate and arylsulfonyl hydrazide are used as nucleophiles,and the activation of benzyl quaternary ammonium salts can be achieved in the presence of base.At the same time,aryl boronic acid is directly inserted into sulfur dioxide under the catalysis of nickel（II）to obtain the sulfonylation intermediate-sulfinate,and to further synthesize a series of sulfone compounds with quaternary ammonium salt.The specific content is as follows:（1）Synthesis of sulfone by reaction of sodium arylsulfinate with benzyl quaternary ammonium salt.This chapter preliminarily explores the basic conditions for the cleavage of the C-N bond of benzyl quaternary ammonium salt,and studies the possible intermediates of the sulfonylation reaction.Using sodium benzene sulfinate as the sulfonylation reagent,the cleavage of the C-N bond of the quaternary ammonium salt without transition metal catalysis was realized in the presence of Cs₂CO₃.In addition,the reaction has good substrate compatibility,and 34 functionalized arylbenzyl sulfone compounds were synthesized with a yield of up to 92%.（2）Synthesis of sulfone by reaction of arylsulfonyl hydrazide and benzyl quaternary ammonium salt.The cross-coupling reaction of sulfonyl hydrazide and benzyl ammonium salt without transition metal participation was studied.Using Cs₂CO₃ as the base and N-methylpyrrolidone as the solvent,a series of benzyl sulfone compounds could be synthesized at the gram scale.The S-N bond of sulfonyl hydrazide and the C-N bond of quaternary ammonium salt can be broken and the C-S bond can be constructed at the same time.This reaction synthesizes 35 alkylbenzyl sulfone derivatives with a yield of 96%under transition-metal-free conditions.（3）Nickel（II）-catalyzed one-pot synthesis of sulfones from arylboronic acid,Na₂S₂O₅and benzyl quaternary ammonium salt.This reaction uses cheap,stable and low-toxic nickel catalyzed one-pot synthesis of（hetero）aryl alkyl sulfone,which is realized by a one-pot two-step method from three components of readily available boric acid,Na₂S₂O₅and benzyl quaternary ammonium salt.When Ni（OTf）₂ was used as a catalyst,lithium carbonate was used as a base,and 3,4,7,8-tetramethyl-1,10-phenanthroline was used as a ligand,28 functional（hetero）arylbenzyl sulfones with a yield of 40%～88%were synthesized.