Research On Oxyacetamide-Directed Ortho-sulfiliminyl Phenol Synthesis

Development of new methods for constructing ortho-functionalized phenols has always been the research hotspot due to their important application in medicines and materials.In recent years,the synthetic methods of ortho-functionalized phenols from N-phenoxyacetamide via aromatic O-N bond broken and transfer have many advantages,such as,mild reaction conditions,operate simply and wide substrate scope.At present,most of the synthetic methods are focused on constructing C-C bond ortho to phenol,but C-X(X=S,N,O)bond is always involved in lots of drugs or biologically active molecules.Thus,building the ortho-heteroatom substituted phenols are also very significant.This thesis is focused on the C-H sulfenylation/intramolecular rearrangement cascade reaction of N-phenoxyacetamide,and the following two parts of research work have been carried out.1.A bioinspired and biocompatible ortho-sulfiliminyl phenol synthesisIn this work,N-(S-substituted)phthalimides served as the sulfenylation reagent,reacted with N-phenoxyacetamide in the presence of CsOAc to synthesize the ortho-sulfiliminyl phenols.Combining an O-N bond in N-phenoxyacetamide with an X-S(X=N,O)bond in sulfenylation reagents can generate a C-S bond and an S=N bond in ortho-sulfiliminyl phenols rapidly at room temperature.The newly discovered cascade reaction showed excellent chemoselectivity and a wide substrate scope of both oxyamines and sulfenylation reagents.Moreover,the method utilized the leaving acetamide moiety of the directing oxyacetamide group to construct a sulfilimine functional group without metal catalysts and external oxidants.Consideration of the mild reaction conditions,we demonstrated the potential application of the C-S bond coupling reaction by developing a fluorogenic probe 2-1w based on the coumarin core in PBS buffer,which might be potentially useful in small-molecule fluorogenic labeling.What's more,the C-S bond coupling reaction enabled the first fluorogenic formation of phospholipids,which self-assembled to blue fluorescent vesicles in situ.Those vesicles with good biocompatible have similar component with cell membranes,which contributes them to be important in drug delivery,construction of micro reactors and protein-membrane interactions study.Meanwhile,we also have proposed a rational mechanism via a series of experiments and theoretic calculation2.Synthesis of ortho-sulfiliminyl phenol via an intermolecular sulfur atom transfer cascade reactionIn this work,commercial available thiols served as the sulfenylation reagent,reacted with N-phenoxyacetamide in the presence of CsOAc to synthesize the ortho-sulfiliminyl phenols.Using air as the oxidant,CsOAc catalyzed C-H sulfenylation/intermolecular sulfur transfer cascade reaction to simultaneously construct C-S and S=N bonds in ortho-sulfiliminyl phenols at room temperature.Moreover,this cascade reaction possesses high atom efficiency and generates water as the sole by-product.Importantly,the reaction has a wide substrate scope and can be conducted on a gram scale with excellent reaction efficiency.On the basis of a series of experiments together with previous reports on sp2 C-H sulfenylation,a plausible mechanism has been proposed.