Disconnection with Participation of Two Functional Groups

Abstract

The concept of charge alteration in compounds with one functional group and the resulting match or mismatch of partial charges in compounds with two functional groups is introduced. The favorable relation of oxygen functionalities in a 1,3- and 1,5-dioxygenated pattern supporting logical disconnections is demonstrated. The Mannich reaction, Michael addition and Robinson annelation are presented as synthetic approaches to this target molecule based on illogical disconnections. Diastereo- and enantioselective (asymmetric) aldol reactions are presented and the mechanism for the preferred formation of syn/anti products discussed. Examples of non-catalytic and catalytic asymmetric aldol and Mannich reactions are given and their mechanistic aspects and experimental protocols presented. Asymmetric syntheses of optically pure compounds with a 1,3-CO pattern (α-alkyl-β-hydroxy carboxylic acids, β-hydroxy ketones, dihydropyranones) and asymmetric Mannich reactions on the route to the optically pure herbicide (S)-fenpropimorph, (S)-phenylglycine and (2S, 3R)-α-amino-γ-keto acids are discussed.