C-N And C-C Bonds Constructive Reaction With Formic Acid:Indirect Utilization Of Carbon Dioxide

Formic acid is an eco-friendly,biocompatible and easily available C₁ source,it can be prepared from hydrogenation of CO₂,and can release CO₂ in the presence of catalyst.Therefore,reactions using formic acid as C₁ synthon can be considered as indirect utilization of CO₂.Compared with CO₂,formic acid is a nontoxic liquid and has the characteristics of convenient storage and transportation,easy operation and has low requirement for equipment?pressure aspect?.In recent years,employing formic acid as a hydrogen storage material and a multifunctional C₁ synthon has attracted wide attention.This protocol focuses on the application of formic acid as C₁resource in coupling reaction with different nucleophilic reagents,such as nitrogen nucleophile and carbon nucleophile.In this way,C-N and C-C bonds can be constructed to achieve the synthesis of N-methylamines and 3,3'-bisindolylmethanes?BIMs?.The main results are as follows:A non-noble copper-catalyzed protocol for N-methylation reaction with formic acid as a C₁ source is reported for the first time.A broad range of primary amines,secondary amines and imine can convert into corresponding methylamines in 37-98%yields using phenylsilane as a reductant under 80 ^oC.Gram-scale experiment indicates this strstegy is practical.The control experiments show that there are two pathways of this N-methylation reaction,including silylacetal intermediate pathway and amide intermediate pathway.Further experiental results reveals that silylacetal intermediate pathway is the major one for Cu?OAc?₂ catalytic system.An effective Fe₂?CO?₉ catalytic system is reported for C-N bonds constructive reaction.Primary and secondary aromatic amines can convert into corresponding methylamines in 28-94%yields using formic acid as C₁ source.Notablely,this Fe₂?CO?₉ catalytic system is compatible with aliphatic carboxylic acids,which can realize the N-alkylation process of carboxylic acids.Control experiments show that there are also two pathways of this C-N bonds constructive reaction,those are silylacetal intermediate pathway and amide intermediate pathway.And the Fe₂?CO?₉catalytic system mainly get through amide intermediate pathway.A straightforward Lewis acid-promoted protocol for bridging indoles with formic aid/carboxylic acids to afford 3,3'-bisindolylmethanes?BIMs?is developed for the first time.Formic acid/carboxylic acids can act as alkylation agents under the reduction of hydrosilane to achieve BIMs through the reductive coupling process with indoles.This methodology avoids employing the air-sensitive aldehydes,which are necessary alkyl sources in BIMs traditional synthesis.A broad range of substituted indoles can convert into corresponding BIMs with formic acids at room temperature and under neat conditions.Notablely,this protocol has a excellent compatibility with carboxylic acids?36-87%yield of BIMs?.Control experiments suggest a feasible pathway involving Lewis acid-mediated reduction of the carboxylic acid to the aldehyde and subsequent Friedel-Crafts reaction between indole and aldehyde.This strategy offers an alternative approach for directly synthesis BIMs with formic acid/carboxylic acids,at the meanwhile,constructing C-C bond with formic acid/carboxylic acids and indoles under the reduction of hydrosilane.