Simple and efficient routes to substituted oxazolidine and spiro-oxindole systems by one-pot synthetic strategies

Abstract

Simple and efficient strategies towards the synthesis of substituted spiro-oxindole and oxazolidine systems by one-pot multi-component catalyst-free reactions utilising aryl aldehydes and a-amino acids have been developed. Owing to their complicated structure and ring strain spiro-oxindole moieties are not easily synthesised. In either route 1,3-dipolar cycloadditions involving non-stabilised azomethine ylides as intermediates, generated in situ from amino acids and aldehydes, with the dipolarophile present in the reaction mixture viz. (E)-bnitrostyrene, were utilised. The route to substituted oxazolidines involved cycloaddition to the C=O bond of a second molecule of the aldehyde.

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives

“…A more detailed account of their work appeared in 1988, where proline (50) was reacted with various aromatic aldehydes 2 to afford, with complete regioselectivity, the hexahydropyrrolo[2,1-b]oxazoles 52 and 53, with the trans-2,3-oxazolidine 52 being either the exclusive or major stereoisomer formed [67][68][69]. The stereoselectivity of the cycloaddition was governed by both the ylide stereochemistry, with the anti-azomethine ylide 51 being favored, and the mutual orientation of the dipole and dipolarophile (Scheme 12, Table 7).…”