Synfacts 2007(4): 0399-0399  
DOI: 10.1055/s-2007-968338
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Inverse-Electron-Demand Diels-Alder Reactions

Contributor(s): Mark Lautens, Praew Thansandote
J. Esquivias, R. G. Arrayás, J. C. Carretero*
Universidad Autónoma de Madrid, Spain
Further Information

Publication History

Publication Date:
23 March 2007 (online)

Significance

A nickel-catalyzed asymmetric inverse-electron-demand Diels-Alder reaction of N-sulfonyl-1-aza-1,3-dienes with vinyl ethers leads to functionalized piperidines. A Lewis acidic nickel complex, Ni(ClO4)2, is required in 10 mol% and the DBFOX-Ph ligand provides good yields, high endo selectivities and excellent enantiocontrol. Variations in the position of the azadiene are generally well tolerated; variations in the vinyl ether and especially substitutions at the iminic carbon are more problematic. To illustrate the synthetic utility of the products, Lewis acid mediated nucleophilic displacement of the alkoxy group and subsequent trapping with a hydride or Grignard reagent affords chiral [1,2,4]benzothiadiazine-5,5-dioxides, which are potential drugs for memory/learning disorders and neurodegenerative dis­eases.