Organokatalytische Asymmetrische Synthesen von Dihydrobenzofuranen und Isochroman-1-onen

摘要

The aldolization is an elementary reaction to form carbon-carbon bonds with high stereoselectivity wherefore it plays an important role especially in organocatalysis. The organocatalytic intermolecular aldol reaction is well established. However, intramolecular aldol reactions are less well developed. Previously, the (S)-proline catalyzed 5-enolexo exo trig aldolization of O-acetonyl salicylaldehydes was described by our group. This reaction offered the possibility to establish the first organocatalytic asymmetric total synthesis of the biologically active natural product smyrindiol. The aldol product was obtained in virtually complete diastereo- and enantioselectivity (de 95%, ee 99%), and smyrindiol was obtained in 15 steps in an overall yield of 6.3%. By exchanging the O-acetonyl salicylaldehyde substrates with 2-oxopropyl 2-formylbenzoate derivatives the 6-enolexo exo trig aldolization afforded the corresponding isochroman-1-ones in good yields (64 to 88%) and excellent diastereo- and enantioselectivities (de 87 to 95%, ee 84 to 99%). The isochroman-1-one heterocyclic unit can be found as a characteristic feature in various natural products such as the naturally occurring carbazolelactone alkaloids. The recently established 6-enolexo aldolization potentially opens a new synthetic pathway to natural products like these. Furthermore the aldol reaction to Isochroman-1-ones could be transferred to the synthesis of isochorman-1-ones via Michael and Mannich reactions. The corresponding chalcones and nitrostyrenes lead to the desired products with 55 to 67% enantiomeric excess. The Mannich reaction gave the corresponding Isochroman-1-one with 70% yield as single stereoisomer.The intramolecular Mannich reaction to the corresponding dihydrobenzofurane affords promising diastereo- and enantioselectivities (de95%, ee 94%). Due to side reactions the yields were moderate (27%).