Organocatalytic asymmetric synthesis of 3,3-disubstituted oxindoles having vicinal quaternary stereocenters Banni Preet Kaur 1 , Jasneet Kaur 2 , Nasarul Islam 2 , Pankaj Chauha 3 , Prof. Swapandeep Singh Chimni 1 1 Guru Nanak Dev University, India, 2 Govt. Degree College, India, 3 Indian Institute of Technology Jammu,India The asymmetric synthesis of molecules and complexes having one or more quaternary stereocenters using simple and mild reaction conditions is a challenging research target in organic chemistry particularly due to the steric encumbrance, which hinders the achievement of high enantioselectivity in such molecules. Additionally, construction of chiral molecules having vicinal quaternary stereocenters further enhances the complications as it limits the substrate scope and may sometimes demand harsh reaction conditions. Use of chiral organic molecules as organocatalysts is a viable approach leading to the synthesis of complex molecular frameworks under mild reaction conditions. On the other hand, the 3,3-disubstituted oxindole is a ubiquitous framework present in various naturally occurring compounds as well as artificially synthesized bioactive molecules and drugs. Functionalization at the C-3 of oxindole is one of the main factors contributing towards the bioactivity of the final molecule. The past literature possesses various reports discussing the asymmetric synthesis of 3,3-disubstituted oxindole derivatives. However, the number of reports presenting the synthesis of 3,3-disubstituted oxindole derivatives having adjacent quaternary stereocenters are quite few. In this context, we were interested in development of methodology for the asymmetric synthesis of 3,3-disubstituted oxindole derivatives having adjacent quaternary stereocenters. Thus, the Mannich reaction between isatin ketimines and α -acetoxy- β -keto esters has been successfully carried out using Cinchona derived thiourea under ambient conditions to procure the chiral oxindole derivatives in good to high yields, up to 93% with excellent enantio- as well as diastereoselectivity, up to 99% ee and 20:1 dr (Scheme 1) .
Scheme 1 References 1. Christoffers, A. Baro, Adv. Synth. Catal. 2005 , 347 , 1473 – 1482. 2. V. Ley, Quaternary Stereocenters–Challenges and Solutions for Organic Synthesis , John Wiley & Sons, 2006 . 3. Y. Cao, F. Zhou, J. Zhou, Acc. Chem. Res. 2018 , 51 , 1443 – 1454. 4. Zhou, L. Zhu, B.-W. Pan, Y. Shi, Y.-L. Liu, J. Zhou, Chem. Sci. 2020 , 11 , 9341 – 9365. 5. M. Ready, S. E. Reisman, M. Hirata, M. M. Weiss, K. Tamaki,T. V. Ovaska, J. L. Wood, Angew . Chem. Int. Ed. 2004 , 43 , 1270 – 1272
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