![]() In this work, we discovered that methyl isocyanide operates under a mechanism of convertible isocyanides (CICs), and could be thought of as a synthetic equivalent to ‘CO’ for insertion into the 2-indolinone backbone (shown in Scheme 1). We noted that when methyl isocyanide was used for the Ugi-4CR and the subsequent post-intramolecular transamidation was performed under acidic conditions, particularly in the presence of TFA, the reaction led to 3-substituted 2-indolinones in a three-step process. In previous efforts to study 3-substituted 2-indolinones through a three-step post-Ugi-4CR/Bechamp type-reduction followed by a transamidation sequence strategy, we came across interesting observations. reported 3-substituted-2-indolinones via a microwave-assisted post-Ugi-4CR/Buchwald–Hartwig reaction and another similar approach was illustrated by Van der Eycken et al. There have been other groups in the past, including our own research group, who have reported on post-modified Ugi-four-component synthetic strategies ( Scheme 1) towards the synthesis of 2-oxindoles and spiro-2,5'(1' H)-diones and spiro-2,5'-diones. For these and other reasons, we became interested in synthesizing spiro-2,5'(1' H)-dione and spiro-2,5'-dione scaffolds (a class of spirocyclic oxindole γ-lactams). However, finding a simple and efficient synthetic method for these molecules that allows for structural diversity is also important but not necessarily trivial. Significant efforts have been made to design creative synthetic strategies for spirocyclic oxindole molecules, of which, isatin-based domino reactions have proved to be very versatile and readily achievable. The synthesis of spirocyclic oxindoles has always been of key interest to organic chemists because of significant biological activity and their presence in naturally occurring molecules. Developing new, post-modified Ugi-four-component reaction (Ugi-4CR) transformations in domino cyclization sequences are very important for achieving unprecedented chemical bonds and functionality towards the construction of synthetic scaffolds. These reactions are appealing in that they are atom economical, simple and generate ample molecular diversity with the ease of using readily available starting materials. The Ugi-multicomponent coupling reaction, followed by post-modification transformations involving tandem reaction sequences and the Ugi–deprotection–cyclization (UDC) strategies have been exploited as powerful tools allowing access to biological and pharmaceutical high-value heterocyclic scaffolds.
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