Organocatalytic synthesis of spiro[pyrrolidin-3,3'-oxindoles] with high enantiopurity and structural diversity.
The privileged spiro[pyrrolidin-3,3'-oxindole] derivatives exhibit important biological activities. An enantioselective organocatalytic approach to the rapid synthesis of spiro[pyrrolidin-3,3'-oxindole] derivatives with high enantiopurity and structural diversity is described. The asymmetric catalytic three-component 1,3-dipolar cycloaddition of a broad range of methyleneindolinones with aldehydes and amino esters in the presence of chiral phosphoric acid provides spirooxindole derivatives in high yield with unusual regiochemistry and excellent stereoselectivities (up to 98% ee) under mild conditions. The straightforward construction of spirooxindole skeletons with high stereo- and regioselectivity suggests a new avenue to medicinal chemistry and diversity-oriented synthesis. Theoretical calculations disclosed that both the azomethine ylide and the methyleneindolinone are hydrogen-bonded with the phosphoric acid, which accounted for the high enantio- and regioselectivity and indicated that the unusual regioselectivity results from the stabilization stemming from the favorable pi-pi stacking interaction between the oxo-indole ring and the conjugated esters.
Chen
Xiao-Hua
XH
Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China.
Wei
Qiang
Q
Luo
Shi-Wei
SW
Xiao
Han
H
Gong
Liu-Zhu
LZ
D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D007536:Isomerism; D015394:Molecular Structure; D000078183:Oxindoles; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D007211:Indoles; D000078183:Oxindoles; D011759:Pyrrolidines; D013141:Spiro Compounds; C022960:2-oxindole