Tin Powder-promoted One-pot Synthesis Of 3,3-disubstituted-2-oxindoles Derivatives

Oxindole framework widely exists in some bioactive natural products and pharmaceutically active compounds.Among them,3-spiro-fused or 3,3-disubstituted oxindoles are recognized as valuable compounds for drug discovery,and also served as key intermediates for the synthesis of many kinds of drug candidates.On the other hand,organotin compounds such as stannanes usually display good stability toward heat,hydrolysis and oxidation,tolerance to functional groups,and high selectivity in organic reactions.However,most of stannanes are toxic.Some studies show that organotin reagents can be formed in situ from tin powder in reactions and then directly react with substrates,which avoids the use of toxic stannanes.Hence,we will maily discuss tin powder-promoted one-pot reaction for the synthesis of3-spirooxindoles and 3,3-disubstituted oxindole derivatives.Thesis is consisted of four charpters:Chapter one:The development in the synthesis of 3,3-disubstituted-2-oxindoles derivativesRecent progress in the synthesis of 3,3-disubstituted-2-oxindoles derivatives is reviewed in this charpter.According to the types of substituents on the 3-position of2-oxindoles,the classification of 2-oxindoles was done and then the methods for the preparation of 3,3-disubstituted 2-oxindoles derivatives were introduced.Chapter two:Tin powder-promoted one-pot synthesis of 3-spiro-fused or 3,3-disubstituted-2-oxindolesA convenient and efficient method for the constructions of 3-spirooxindole derivatives or 3,3-disubstituted-oxindoles has been developed from one-pot reactions of isatins,hydrazides or aromatic amines,2-?bromomethyl?acrylic ester and tin powder in the presence of a catalytic amount of Br?nsted or Lewis acid.After optimizing the conditions and investigating the substrates scopes of the reactions,a series of spirocycloheptane oxindoles or 3,3-disubstituted-oxindoles in good to excellent yields?up to 99%?.The process has good tolerance to the functional groups and avoids the use of toxic stannanes and allows easy operation in mild conditions.It is also proved that hydrazides are more favorable for intramolecular cyclization than amines.Chapterthree:Tinpowder-promotedone-potsynthesisof3-allyl-3-acylhydrazonyl-2-oxindoles or 3-allyl-3-amino-2-oxindolesA facile and efficient one-pot synthesis of 3-allyl-3-acylhydrazonyl-2-oxindoles or 3-allyl-3-amino-2-oxindoles is developed through tin powder-promoted reactions of isatins,hydrazides or amines,and allylic bromide by using Ni?ClO₄?₂.6H₂O as catalyst.The process uses allyltin reagent generated in situ from tin powder and allyl bromide,which makes the operation easier,and yields of the products are good to excellent.Among them,the highest yield of reaction can reach 99%.Chapterfour:Tinpowder-promotedone-potsynthesisof3-trifluoroethylamino-2-oxindolesthe trifluoromethyl incorporated at the?-position to nitrogen is the important synthetic block in pharmaceutical and agro-chemistry,with such compounds often having enhanced lipophilicity and metabolic stability when present in small molecules,a tin powder promoted one-pot synthesis of 3-Trifluoroethylamino-2-oxindole is initial research by the treatment of isatin,2,2,2-Trifluoroethylamine,allylic bromide and trifluoroethylamine in the presence of TfOH as catalys.