Development of a syn‐Selective Mannich Reaction of Aldehydes with Propargylic Imines by Dual Catalysis: Asymmetric Synthesis of Functionalized Propargylic Amines. Issue 21 (13th April 2016)

• Record Type: Journal Article
• Authors: Lapuerta, Irati; Vera, Silvia; Oiarbide, Mikel; Palomo, Claudio
• Is Part Of: Chemistry. Volume 22:Issue 21(2016)
• Page Start: 7229
• Page End: 7237
• Publication Date: 2016-04-13
• Subjects: aminoalcohols -- asymmetric catalysis -- dual catalysis -- Mannich reaction -- propargylic amines; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201600635
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Direct coupling of enolizable aldehydes with C ‐alkynyl imines is realized affording the corresponding propargylic Mannich adducts of syn configuration, thus complementing previous methods that gave access to the anti ‐isomers. The combination of proline and a urea Brønsted base cocatalyst is key for the reactions to proceed under very mild conditions (3–10 mol % catalyst loading, dichloromethane as solvent, −20 °C, 1.2 molar equivalents of aldehyde) and with virtually total stereocontrol ( syn / anti ratio up to 99:1; ee up to 99 %). Some possibilities of further chemical elaboration of adducts are also briefly illustrated. Abstract : Propargylic Mannich adducts of syn relative configuration are now accessible in essentially diastereo‐ and enantiopure form from the direct reaction between aldehydes and C ‐alkynyl imines (see scheme), thus complementing previously reported methods to access the anti ‐adducts. The reactions are general and proceed in very mild conditions (CH2 Cl2, −20 °C) without formation of side products.