Mn(III)-Initiated Facile Oxygenation of Heterocyclic 1,3-Dicarbonyl Compounds

Abstract

The Mn(III)-initiated aerobic oxidation of heterocyclic 1,3-dicarbonyl compounds, such as 4-alkyl-1,2-diphenylpyrazolidine-3,5-diones, 1,3-dialkylpyrrolidine-2,4-diones, 3-alkyl-1,5-dimethylbarbituric acids, and 3-butyl-4-hydroxy-2-quinolinone gave excellent to good yields of the corresponding hydroperoxides, which were gradually degraded by exposure to the metal initiator after the reaction to afford the corresponding alcohols. The synthesis of 30 heterocyclic 1,3-dicarbonyl compounds, the corresponding hydroperoxides and the 10 alcohols, their characterization, and the limitations of the procedure are described. In addition, the mechanism of the hydroperoxidation and the redox decomposition of the hydroperoxides are discussed.

Mn(III)‐catalyzed Aerobic Oxidation of 3‐Alkyl‐4‐hydroxy‐1H‐pyrrol‐2(5H)‐ones in the Presence of 1,1‐Diarylethenes. Synthesis of Stable 8‐Aza‐1‐hydroxy‐2,3‐dioxabicyclo[4.3.0]nonan‐7‐one Framework

“…Twenty‐two different pyrrolidine‐2,4‐diones 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h , 1i , 1j , 1k , 1l , 1m , 1n , 1o , 1p , 1q , 1r , 1s , 1t , 1u , 1v were synthesized by Dieckmann condensation of the corresponding alkanoyl‐protected alkylaminoacetates that were prepared by the reaction of alkylaminoacetates with alkanoyl chlorides . The prepared 2,4‐pyrrolidinediones 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h , 1i , 1j , 1k , 1l , 1m , 1n , 1o , 1p , 1q , 1r , 1s , 1t , 1u , 1v existed as an enol form, that is, 1,3‐dialkyl‐4‐hydroxy‐1 H ‐pyrrol‐2(5 H )‐ones, in solution . With the pyrrolidine‐2,4‐diones in hand, we preliminarily examined the reaction of 1‐benzyl‐4‐hydroxy‐3‐methyl‐3‐pyrrolin‐2‐one ( 1a ) with 1,1‐diphenylethene ( 2a ) in the presence of Mn(OAc) 3 •2H 2 O according to Nguyen's procedure .…”

“…Construction of the stable 8‐aza‐1‐hydroxy‐2,3‐dioxabicyclo[4.3.0]nonan‐7‐one framework was achieved by the Mn(III)‐catalyzed aerobic oxidation of alkyl‐substituted tetramic acid derivatives 1 with 1,1‐diarylethenes 2 . Because a peroxy bond of the hydroperoxides and endoperoxides tends to undergo homolytic cleavage in vivo , the 8‐aza‐1‐hydroxy‐2,3‐dioxabicyclo[4.3.0]nonan‐7‐ones 3 may also have some biological activities such as antimalarial, insecticidal, bactericidal and cytotoxic activities, and an inhibitory effect toward mRNAs in cells .…”

“…Manganese(II) acetate tetrahydrate, Mn(OAc) 2 •4H 2 O, was purchased from Wako Pure Chemical Ind., Ltd. Manganese(III) acetate dihydrate, Mn(OAc) 3 •2H 2 O, was prepared according to the method described in the literature . 3‐Alkyl‐4‐hydroxy‐1 H ‐pyrrol‐2(5 H )‐ones 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h , 1i , 1j , 1k , 1l , 1m , 1n , 1o , 1p , 1q , 1r , 1s , 1t , 1u , 1v were prepared by the reaction of the corresponding (alkylamino)acetates with acyl chlorides . The prepared 2,4‐pyrrolidinediones 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h , 1i , 1j , 1k , 1l , 1m , 1n , 1o , 1p , 1q , 1r , 1s , 1t , 1u , 1v exist as an enol form (1,3‐dialkyl‐4‐hydroxy‐1 H ‐pyrrol‐2(5 H )‐ones) in an aprotic polar solvent, such as DMSO‐ d 6 .…”

“…Tetramic acids, that is, pyrrolidine‐2,4‐diones, are well known as a heterocyclic core of natural products that have various biological activities such as antibacterial and cytotoxic activities , endothelin and glycine site N ‐methyl‐ d ‐aspartate receptor antagonists . On the other hand, endoperoxides and hydroperoxides are an important oxidation intermediate, which also have various biological activities . Therefore, it would be expected that 8‐aza‐2,3‐dioxabicyclo[4.3.0]nonanes that have a fused tetramic acid core and an endoperoxide unit might be a candidate having stronger biological activities (Scheme ).…”

4-Acetyl-2-hydroxy-2,5-dimethylfuran-3(2H)-one

“…The 1,3-dicarbonyl radical A could be trapped by a radical scavenger such as xanthene and 2,6-di-tert-butyl-4methylphenol (BHT) [24]. The dimeric compound B should be more reactive than Hacac, thus compound B would be further oxidized and followed by capture of the dissolved molecular oxygen to produce the peroxy radical C. Radical C should be reduced by Mn(II), affording the peroxy anions D and the reproduced Mn(III) species [25,26]. The peroxy anion D must be converted to 4-acetylhexane-2,3,5-trione (H) via the 1,2-dioxetane formation [27].…”