Studies On 1,3-dipolar Cycloaddition Reactions Toward Spirooxindoles

The spirooxindole ring system has been recognized as a key scaffold in a large family of natural products and biologically active molecules.For example,the spiroxindole nucleus as a structural centerpiece has been incorporated into a plethora of highly pronounced bioactive molecules on account of their wide spectrum of therapeutically remarkable influences on anti-inflammatory,anti-cancer,anti-microbial properties and many others.Additionally,these spirooxindole nucleus have been used as significant synthetic intermediates for the synthesis of natural alkaloids and pharmacologically important compounds.In this context,however,although a great quantity of the preparation of spiro[pyrrolidine-3,3’-oxindoles] have been developed,only a few synthetic methods toward spiro[pyrrolidine-2,3’-oxindoles] are available.Therefore,it is of great value to develop a method for the efficient synthesis of such molecules.In this thesis,1,3-dipolar cycloaddition process to form spiroxindole derivatives was developed.In particular,a diverse array of biologically and pharmacologically spiroxindole compounds with novel and complex structures were obtained with high yields and excellent diastereoselectivities from simple and readily available starting materials.(1)A DBU-catalyzed three-component 1,3-dipolar cycloaddition of azomethine ylide generated in situ to form a series of new spiro[pyrrolidine-2,3’-oxindoles] derivatives bearing a variety of functional groups and featuring four consecutive chiral centers was established in high yields with good to excellent diastereoselectivities(up to 99% yield,>20:1 dr).Additionally,the catalytic asymmetric construction of spiro[pyrrolidine-2,3’-oxindoles] derivatives was achieved in high yields and excellent diastereoselectivity,though with poor enantioselectivity under the catalysis of chiral phosphoric acid.(2)A series of dispiro[pyrrolidine-2,3′-oxindole] cores were synthesized by direct assembly of 3-aminooxindole,benzaldehyde and methylene isatin derivatives using DABCO as the catalyst.The dispiro cycloadducts were acquired in good to high yields with good to excellent diastereoselectivities(up to 97% yield,up to 96:4 dr).