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Sequential Metal-Free Thermal 1,3-Dipolar Cycloaddition of Unactivated Azomethine Ylides
Verónica Selva1,2,3, Elisabet Selva1,2,3,4, Pedro Merino5
1Departamento de Química Orgánica . Facultad de Ciencias, Universidad de Alicante , 03080 Alicante , Spain.
Abstract:
The thermal 1,3-dipolar cycloaddition of unactivated azomethine ylides derived from allylamine and aromatic or heteroaromatic aldehydes with maleimides and 1,1- and 1,2-bis(phenylsulfonyl)ethylene affords endo-2,5- trans cycloadducts in moderate to good yields. DFT calculations provide evidence that the diastereoselectivity observed depends on the isomerization between S- and W-ylides according to Curtin-Hammett's principle. DFT calculations also explain the different diastereomeric ratio observed for 2-pyridyl and 2-thienyl derivatives in which the isomerization is not possible due to the competitiveness between isomerization barrier and the rate-limiting step (ylide formation barrier). This methodology is applied to the diastereoselective synthesis of a tricyclic thrombin inhibitor.
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