Highly Efficient Synthesis Of Sulfoximine Derivatives

Sulfoximine is a kind of compound that containing O=S=N double bonds moiety in the molecule.Compared with organic sulfones,the introduction of nitrogen atom in sulfoximine have greatly changed the base properties of the these compounds,and as a result the nucleophilicity and reactivity were enhanced,respectively.Sulfoximine derivatives are important raw materials and key synthetic intermediates in organic synthesis.The S=N group can also be used as a good nitrogen-containing directing group in direct C-H functionalization reactions,or as chiral auxiliary or ligand in asymmetric catalysis.In this dissertation,based on our previous achievements in the studies of sulfoximines,we herein developed several simple and efficient methods for the rapid generation of novel sulfoximine derivatives with potential pharmaceutical or medicinal activity.The main contents are summarized as follows:?1?The recent advancements in the synthesis of sulfoximine derivatives are reviewed.The direct N-H functionalizations and C-H bond activations of sulfoximines are briefly discussed,including the mechanisms of some novel reactions.?2?A Pd/norbornene co-catalyzed tandem C-H activation/annulation Catellani reaction was disclosed,to give several types of cyclic sulfoximines in a one-pot and one-step synthetic protocol.When aryl iodides bearing otho substitutions were employed,tandem annulation took place to give the corresponding fused tricyclic products.However,when meta-EWG-substituted iodobenzenes were used,the bridged tetracyclic compounds that containing eight-membered heterocyclic structures were obtained.Moreover,employment of excess amount of sulfoximine resulted in the formation of compounds bearing two sulfoximine moieties.To understand the mechanisms by DFT calculation,the key reductive elimination process of the Pd^IVintermediates were found to be controlled by electronic effect,thus producing the different heterocycles in highly selective manners.?3?Highly efficient Curtius rearrangement reactions of free NH-sulfoximines with acyl azides were reported,to afford unsymmetrical sulfoximine ureas in up to quantitative yields.Mechanically,nitrene species derived from acyl azides under heating and weak basic conditions were firstly generated,which subsequently induced the following addition reactions with free NH-sulfoximines to give the observed products.It should be noted that the reaction could be easily scaled up to gram-scale preparation,and only release nontoxic N₂ as the sole byproduct,and is potentially suitable for industrial synthesis of the related urea products.