Regioselectivity-Tunable Self-1,3-Dipolar [3+3] Cyclizations of Azomethine Ylides To Assemble Dispirooxindole-piperazines

A series
of novel 2,3- or 2,5-dispirooxindole-piperazine ring systems
were efficiently constructed through the acid-promoted self-1,3-dipolar
[3+3] cyclizations of azomethine ylides derived from isatin with various
primary or cyclic secondary amines. Interestingly, the regioselectivity
of this self-[3+3] cyclization could be effectively tuned by varying
the structural features of substrates. The unprecedented 2,5-dispirooxindole-piperazine
skeleton was achieved in good diastereoselectivity by employing 1,2,3,4-tetrahydroisoquinoline,
while using pyrrolidine or glycine methyl ester furnished the 2,3-dispirooxindole-piperazine
scaffold in excellent diastereoselectivity (only a single isomer formed).