Umpolung α-regioselective 1,3-dipolar cycloaddition and internal recycle of byproduct as two key strategies: access to diverse chiral bipyridines

Abstract

Herein, the first example of umpolung α-regioselective 1,3-dipolar cycloaddition of optically pure perhydroindole-2-carboxylic acid 1a with pyridinecarboxaldehydes 2 is described. By using this practical method, a wide range of conformationally rigid chiral perhydroindole-bipyridine compounds 3 was readily prepared with good results, and their diastereoisomers can also be isolated by column chromatography. The further diverse derivatizations of products 3 into 1,2-oxazinane-containing diverse bipyridine compounds 6 has also been well demonstrated with m-CPBA as the oxidant. Notably, the key to the high efficacy of the chemical transformations is attributed to the in situ-generated byproduct 3-chlorobenzoic acid that can act as an internal reuse reagent for the following ring-opening and subsequent ring-expansion sequences mediated by formal oxygen atom insertion into the carbon–nitrogen bond.