Decarboxylative, Diastereoselective and exo-Selective 1,3-Dipolar Cycloaddition for Diversity-Oriented Construction of Structural Spiro[Butyrolactone–Pyrrolidine–Chromanone] Hybrids

Abstract

Inspired by the chemistry and biology of butyrolactones, pyrrolidines, and chromanones, we successfully developed a simple domino 1,3-dipolar cycloaddition of homoserine-lactone-derived azomethine ylides for the construction of biologically important spiro[butyrolactone–pyrrolidine–chromanone] hybrids in the presence of Et₃N as a catalyst under mild conditions. The reaction is based on the application of carboxylic-acid-activated chromones as dienophiles, followed by a decarboxylation process. This reaction displayed good substrate tolerance and gave the desired products in moderate to good yields with high diastereoselectivities (up to 85% yield and >20:1 diastereomeric ratio) via an exo-transition state. This is the first example of an introduction of a chromanone moiety into a spiro[butyrolactone-pyrrolidine] framework, which might be valuable in medicinal chemistry.

Key words

1,3-dipolar cycloaddition - chromones - spiro compounds - azomethine ylides - pyrrolidines - lactones

Publication History

Received: 24 April 2021

Accepted after revision: 24 June 2021

Accepted Manuscript online:
24 June 2021

Article published online:
15 July 2021

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