One-Pot Organocatalytic Domino Michael-Aldol and Intramolecular S_N2 Reactions. Asymmetric Synthesis of Highly Functionalized Epoxycyclohexanone Derivatives

Abstract

The development of the organocatalytic asymmetric one-pot Michael-Darzens condensation giving highly functionalized complex epoxycyclohexanone derivatives with up to four chiral centers is presented. Depending on the reaction conditions, either the polysubstituted 7-oxa-bicyclo[4.1.0]heptan-2-one ring system or 2-chloro-cyclohex-2-enone derivatives can be formed. For the former class of compounds a high diversity in substitution pattern is demonstrated, and the optically active products are obtained in excellent diastereo- and enantioselectivities. The potential synthetic applications of the products have been demonstrated by performing a series of highly diastereoselective transformations leading to optically active products useful for the life-science industry. Furthermore, mechanistic investigations on the formation of the chiral centers in the optically active epoxycyclohexanone are presented.

Lewis‐Base‐Katalyse in der organischen Synthese

“…(2) in Schema 41]. Lewis-Base-katalysierte Michael-Additionen bilden außerdem den ersten Schritt in vielen Lewis-Basekatalysierten Reaktionskaskaden, darunter Aldol-Aldol- [180] und Michael-Darzens-Reaktionen, [181] Cyclopropanierungen [182] und Epoxidierungen. [183] Die Entwicklungen auf diesem Gebiet der Lewis-BaseKatalyse waren darüber hinaus von Vorteil für asymmetrische konjugierte Reduktionen von Carbonylverbindungen, die mit herkömmlichen katalytischen Methoden schwierig sind.…”

Multicatalytic, asymmetric Michael/Stetter reaction of salicylaldehydes and activated alkynes

“…Especially powerful in its application to total synthesis, asymmetric tandem catalysis has enabled rapid access to enantioenriched products with high levels of selectivity (1, 4-8, 10, 11). Although most examples exploit a single catalyst to promote multiple, sequential transformations (12)(13)(14)(15)(16)(17)(18)(19), systems relying on two or more catalysts have been reported (2,3,11,20). Inherent in any multiple catalyst system is the challenge of compatibility.…”

1,3-Dicarbonyl compounds in stereoselective domino and multicomponent reactions

“…90 The enantioselective Michael addition is catalyzed by the prolinol derivative and is followed by a Darzens reaction due to the presence in the reaction of a base (sodium acetate) to perform the aldol reaction. In a consecutive step the addition of a stronger base (K 2 CO 3 ) deprotonates the alcohol 105 and enables the intramolecular S N 2 reaction to lead to the formation of the epoxide 106.…”