Catalytic asymmetric formal [3+3] cycloaddition of an azomethine ylide with 3-indolylmethanol: enantioselective construction of a six-membered piperidine framework.
A catalytic asymmetric formal [3+3] cycloaddition of 3-indolylmethanol and an in situ-generated azomethine ylide has been established to construct a chiral six-membered piperidine framework with two stereogenic centers. This approach not only represents the first enantioselective cycloaddition of isatin-derived 3-indolylmethanol, but also has realized an unusual enantioselective formal [3+3] cycloaddition of azomethine ylide rather than its common [3+2] cycloadditions. Besides, this protocol combines the merits of a multicomponent reaction and organocatalysis, which efficiently assembles a variety of isatin-derived 3-indolylmethanols, aldehydes, and amino esters into structurally diverse spiro[indoline-3,4'-pyridoindoles] with one all-carbon quaternary stereogenic center in high yields and excellent enantioselectivities (up to 93 % yield, >99 % enantiomeric excess (ee)). Although the diastereoselectivity of the reaction is generally moderate, most of the diastereomers can be separated by using column chromatography followed by preparative TLC.
School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou, 221116 (China), Fax: (+86) 516-83500065. fshi@jsnu.edu.cn.
Feng
F
Shi
Ren-Yi
RY
Zhu
Wei
W
Dai
Cong-Shuai
CS
Wang
Shu-Jiang
SJ
Tu
asymmetric synthesis; cycloaddition; enantioselectivity; multicomponent reactions; organocatalysis; ylides