Polar [3 + 2] cycloaddition of isatin-3-imines with electrophilically activated heteroaromatic N-ylides: Synthesis of spirocyclic imidazo[1,2-a]pyridine and isoquinoline derivatives

• Main Authors: Tayebeh Sattaei Mokhtari, Mohammad Seifi, Vahid Saheb, Hassan Sheibani
• Format: Article
• Language: English
• Published: Elsevier 2019-12-01
• Series: Arabian Journal of Chemistry
• Online Access: http://www.sciencedirect.com/science/article/pii/S1878535215001719

A new synthesis of spiro[imidazo[1,2-a]pyridine-2,3′-indoline]-2′-ones 3a-f and spiro[imidazo[1,2-a]isoquinoline-2,3′-indolin]-2′-ones 5a-d, respectively by polar [3 + 2] cycloaddition reactions of isatin-3-imines with pyridinium and isoquinolinium ylides which are derived from 2-bromoacetophenone, 2,4′-dibromoacetophenone or methyl bromoacetate is described. These cycloaddition reactions consist of the nucleophilic attack of the heteroaromatic N-ylides on isatin-3-imine derivatives. The salient features of these processes include operational simplicity, high yields, and easily accessible starting materials. In addition, Density Functional Theory (DFT) calculations at the M06–2X/6–31 + G(d) level have been performed to investigate the possible transition states and products. The theoretical results are in good agreement with the experimental findings and show that the product 3a is the most stable product and is formed through a kinetically feasible pathway. Keywords: Pyridinium and isoquinolinium ylides, Isatin-3-imines, Spiro[imidazo[1,2-a]pyridine-2,3′-indoline]-2′-ones, Spiro[imidazo[1,2-a]isoquinoline-2,3′-indolin]-2′-ones, Polar [3 + 2] cycloaddition