Synthesis of 2H-1,4-Oxazin-3(4H)-One Utilizing Umpolung Reaction to α-Hydrazonoketone

Abstract

2H-1,4-Oxazin-3(4H)-One Derivatives Are Known to Exhibit a Wide Range of Biological Activities Such as Antifungal, Anticancer, as Receptor Antagonists and Potassium Channel Modulators. In This Report, We Describe That α-Hydrazonoketone Is an Appropriate Substrate for the Umpolung Reaction and a Promising Candidate for the Synthesis of 2H-1,4-Oxazine-3(4H)-Ones. Notably, Umpolung N-Methylation for α-Hydrazonoketone Proceeded Quantitatively in a Mild and Extremely Short Reaction Time, Which Has Been Difficult to Achieve in the Conventional Reactions. Moreover, We Also Developed Tandem Umpolung Reaction/Reduction/N-Acyl-O-Alkylation to Afford 2H-1,4-Oxazin-3(4H)-Ones in High Yield in the Presence of Chloroacetyl Chloride.