Solid-phase synthesis of proline analogs via a three component 1,3-dipolar cycloaddition

• Published in: Tetrahedron letters 1996-05, Vol.37 (21), p.3671-3674
• Main Authors: Hamper, Bruce C., Dukesherer, Daniel R., South, Michael S.
• Format: Article
• Language: English
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/0040-4039(96)00659-4

Preparation of highly substituted pyrrolidines (proline analogs) was achieved by solid-phase organic synthesis using a three component 1,3-dipolar cycloaddition of a resin bound azomethine ylide. The synthesis utilizes a series of hydroxybenzaldehydes attached to Wang's resin via a Mitsunobu coupling followed by reaction with an alpha-amino ester and a maleimide. The solid phase reaction is utilized to obtain 3a as a single component. Alternatively, the reaction may be performed using an equimolar mixture of resins to afford a defined product mixture 4a-i as determined by LC-MS analysis. Preparation of highly substituted pyrrolidines (proline analogs) was achieved by solid-phase organic synthesis using a three component 1,3-dipolar cycloaddtion. The solid phase reaction is utilized to obtain the product as a single component or a defined product mixture using a mixture of resins.