Development And Application Of N-Formylsulfonamides As CO Surrogate

Carbonylation using CO as carbonyl source is a key organic synthesis tool for the construction of aromatic esters,aldehydes,ketones,acids,amides and their derivatives.However,CO is odorless,tasteless,toxic,and inflammable gas,and its transportation and storage rely on pressure-resistant equipment,which limits the use of CO in carbonylation.The dissertation aims to the development of N-formylsulfonamides as new CO surrogate.The structure-activity relationships of N-formylsulfonamides as CO surrogate were evaluated by combining theoretical calculation with experimental verification.The dissertation explored the effect of different substituents on the decarbonylation rates of N-formylsulfonamides as CO surrogate.N-Formylsulfonamides as CO source have been used in alkoxycarbonylation,phenoxycarbonylation,reductive carbonylation and carbonylative Suzuki coupling reaction of aryl halides.Compared with CO and traditional CO surrogates,N-formylsulfonamides as CO surrogate have the advantages of regulating activity by introducing different substituents,low toxicity,good stability,easy synthesis,cheap and easy to obtain.The main research contents are given as follows:(1)Firstly,N-formylsulfonamides with different substituents were synthesized in two steps,then the crystal structures were characterized.The effect of different substituents on the decarbonylation rate of N-formylsulfonamides was analyzed by theoretical calculation with dynamic experimental verification.As a result,the O(3)-C(8)-N(1)-C(9)torsion angle of phenyl-substituted N-formylsulfonamide is the biggest,which makes electron transfer difficult,weakens the conjugative effect,and contributes to the fracture of N-C(O)bond.Dynamic experiments indicated that the decarbonylation rate of phenyl-substituted N-formylsulfonamide was the fastest,and the CO conversion rate reached 90%within 30 minutes.The CO conversion rate of 4-fluorophenyl-substituted N-formylsulfonamide was the second.The CO conversion rate of 4-methoxyphenyl-substituted N-formylsulfonamide was the slowest.The experimental results agreed with the theoretical calculation.(2)Aryl esters were synthesized by alkoxy/phenoxy-carbonylation using N-formylsulfonamide as CO surrogate.In this scheme,42 aryl ester compounds were synthesized using N-formylsulfonamide as CO surrogate,aryl bromides and alcohols or phenols as substrates,Pd(CH3CN)2Cl2 as catalyst,dppb as ligand and sodium carbonate as base.The yield was up to 98%.This method has been successfully applied to the structure modification of natural products.The radical trapping experiment showed that the reaction was not radical reaction.Competitive experiments showed that the decisive step of the reaction was the oxidation addition step.(3)Aryl aldehydes were synthesized by reductive carbonylation with N-formylsulfonamide as CO surrogate.A series of aromatic aldehydes were synthesized using N-formylsulfonamide as CO surrogate,aryl bromides as substrates,triethyl silane as hydrogen source,Pd(PPh3)4 as catalyst,sodium carbonate as base,DMF as solvent.This method has excellent functional group compatibility and provides a new way for the synthesis of aryl aldehydes.(4)Biaryl ketones were synthesized by carbonylative Suzuki coupling reaction with N-formylsulfonamide as CO surrogate.A series of biaryl ketones were synthesized using N-formylsulfonamide as CO surrogate,aryl bromides and arylboric acids as substrates,Pd(CH3CN)2Cl2 as catalyst,dppb as ligand,sodium carbonate as base and toluene as solvent.This method has excellent functional group compatibility and provides a new way for the synthesis of biaryl ketones.