Asymmetric Synthesis Of Multifunctional Spirooxindoles

Spirooxindole has been regarded as a significant scaffold which widely exist in a large family of natural products and biologically active molecules.Additionally,the spirooxindole cores have been used as crucial synthetic intermediates for the synthesis of natural alkaloids and pharmacological molecules.Because of their remarkable pharmaceutical activity on anti-bacterial,anti-viral,anti-cancer and many others,the spiroxindole nucleus have been extensively applied into pharmaceutical preparation.Meanwhile,there are also numerous other frameworks found in nature proved to be pharmaceutically active,such as indole and chromane.In this context,however,although a great quantity of the processes to spirooxindoles have been developed,only a few synthetic methods toward double skeleton spirooxindoles are available.Therefore,it is of great significance to develop a method for the efficient synthesis of such densely functional molecules.In this paper,asymmetric [3+2] cycloaddition process to form double skeletons spiroxindole derivatives has been developed.In particular,a d iverse array of pharmacologically active spiroxindole compounds with excellent optical activity were obtained.This method features such advantage as simple experiments operation,mild reaction conditions,broad reaction scope,high yields and excellent stereoselectivities.Two parts of researches were conducted in this paper:(1)A chiral phosphoric acid catalyzed [3+2] cycloaddition of azomethine ylide generated in situ with 3-nitro-2H-chromenes to deliver a series of densely functionalized polycyclic spirooxindole-chromane adducts featuring four contiguous stereogenic centers,including two tetrasubstituted carbon centers in high yields with good to excellent diastereoselectivities(up to 99% yield,96% ee and >20:1 dr)has been developed.(2)A chiral phosphoric acid catalyzed [3+2] cycloaddition of azomethine ylide generated in situ with diethyl 2-(1H-indol-3-ylmethylidene)propanedioate to deliver a series of double indole skeleton compounds featuring three stereogenic centers,including two tetrasubstituted carbon centers in high yields with good to excellent diastereoselectivities(up to 98% yield,96% ee and >20:1 dr)has been developed.