Diversity-oriented regioselective domino Michael/Aldol reaction of 3-ylideneoxindoles: A direct access to indanol-fused 3-oxindoles

ABSTRACT

A diversity-oriented molecular hybridization strategy has been utilized for the synthesis of 2,3-disubstituted 1-indanol-fused 3-oxindoles through a regioselective domino Michael/Aldol reaction of 3-ylideneoxindoles 1 with malononitrile or cyanacetate ethyle 2. Products bearing consecutive stereocenters consist of an oxindole moiety and an indanol core, were smoothly obtained in high yields (up to 92% yield) with good diastereoselectivity (up to 20:1). This protocol also represents the first construction of indanol-fused 3-oxindole scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis (DOS) and the lead compound discovery. It is also worth mentioning that the reaction was completely regioselective and the competitive regioisomeric products 4 or 5 were not obtained in any case.

GRAPHICAL ABSTRACT

KEYWORDS:

• 3-Ylideneoxindoles
• diversity oriented synthesis
• domino Michael/Aldol reaction
• indanol-fused 3-oxindoles
• regioselective

Additional information

Funding

We are grateful for the financial support from the National Natural Science Foundations of China (Nos. 81560563, 81660576, and 81760625); Excellent creative talents of guizhou province (Qian Jiao He KY Zi [(2015)491] and Qian Ke He Zi [2015]4032, [2017]5609); Project of Guizhou province (Qian Ke He Zi ([2016]5623 and [2015]4010); Innovation Fund for graduate students of Guizhou University (2017027) and Major project of the graduate student education teaching reform (Qian Jiao Yan He JG Zi)[2016]06.