Magnesium Salt Promoted Tandem Nucleophilic Addition-Oppenauer Oxidation Of Aldehydes With Organozinc Reagents

Domino reaction is now widely accepted as a promising green protocol for C-C bond formation, functional group implantation and transformation in a one-pot operation. In this respect, strategies involving reactive organometallics are still rare. The Mg-Oppenauer oxidation of aldehydes?MOOA? has proven to be a greener and practical protocol for ketone synthesis. magnesium salt promoted synthesis of ketones via a tandem nucleophilic addition-oppenauer oxidation of aldehydes using organozinc reagents was demonstrated. The concomitantly formed magnesium salt during magnesium mediated organohalides zincation exhibits high efficacy for nucleophilc addition of organozinc reagents to aldehydes and thereafter Oppenauer oxidation whereby ketones were formed in high to excellent yields. This transformation offers an green and facile procedure for highly functionalized aryl and alkyl ketones preparation. The usefulness of this practical and efficient method was demonstrated in gram-scale synthesis of a non-steroidal anti-inflammatory drug Suprofen.In summary, based on forerunners' work, this paper explores and develops a new method for synthesis of ketones with the reactants of organozinc reagent and aldehydes. Chapter 1: The influence of Main Group Metallic Lewis acids on the formation and reactivity of Grignard reagentsThis mini-review provides a concise overview mainly on the behavior of main group metallic salts derived from lithium, magnesium and aluminum as a powerful tool for regioselective metalation of C-X?X = Cl, Br, I? and C-H bonds. The diverse functions of these metallic salts on the reactivities of Grignard reagents are exemplified primarily choosing aldehyde as the electrophile. Chapter 2: Magnesium Salt Promoted Tandem Nucleophilic Addition-Oppenauer Oxidation of Aldehydes with Organozinc ReagentsIn this chapter, reaction of diethyl zinc and an aromatic aldehyde was selected as a template reaction for optimizing reaction conditions. Then we expand the range of substrate and got a series of aryl and alkyl ketones?All synthetic products were characterized by ¹HNMR, ¹³ CNMR. The method mentioned above has features of easy-operated and higher yield. It is worth mentioning that the ketones are also potential synthetic intermediates. Chapter 3: Tandem Nucleophilic Addition-Oppenauer Oxidation of Aromatic Aldehydes with Functionalized Organozinc ReagentsIn this chapter, uses highly functionalized organozinc reagents and aldehyde as the reaction substrate to synthesize highly functionalized ketones, which are regarded as a template reaction to explore the reaction conditions. Then we expand the range of substrate and got a series of ketones. All synthetic products were characterized by ¹HNMR, ¹³ CNMR. The feasibility of this method has been verified with both high yield and fast reaction rate, which can be considered as a new approach for the synthesis of ketones.