Formation of δ‐Lactones with anti‐Baeyer–Villiger Regiochemistry: Investigations into the Mechanism of the Cerium‐Catalyzed Aerobic Coupling of β‐Oxoesters with Enol Acetates

Abstract

The cerium-catalyzed, aerobic coupling of β-oxoesters with enol acetates and dioxygen yields δ-lactones with a 1,4-diketone moiety. In contrast to the Baeyer-Villiger oxidation (BVO), where the higher substituted residue migrates; in the case of this oxidative C-C coupling reaction, the less substituted alkyl residue undergoes a 1,2-shift. An endoperoxidic oxycarbenium ion comparable to the Criegee intermediate in the BVO is proposed as a reaction intermediate and submitted to conformational analysis by computational methods. As a result, the inverse regiochemistry is explained by a primary stereoelectronic effect. A Hammett analysis using different donor- and acceptor-substituted enol esters provides support for the oxycarbenium ion being the crucial intermediate in the rate determining step of the conversion. An overall mechanism is suggested with a radical chain reaction for the formation of endoperoxides from β-oxoesters, enol acetates and dioxygen with a cerium(IV) species as initiating reagent.

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

“…Although the exact catalytic cycle of our reaction remains to be elucidated, we propose a plausible reaction mechanism based on our observations and known literature precedents (Figure 1B) [57,59,[66][67][68][69]. Under aerobic conditions the catalytic Ce III (OBn)L n species I (in situ derived by the reaction of CeCl 3 (Ce III L n ) with the substrate benzyl alcohol, BnOH) could be oxidized to L n Ce IV -OBn complex II [67][68][69]. During this process O 2 is converted into a superoxide radical anion O 2…”

“…As shown in Figure 1A, the absorption spectrum of the Ce IV (OBn)Cl n complex gradually shifted from λ max = 375 nm to λ max = 325 nm upon irradiation, which indicates a photoinduced Ce IV -OBn homolytic cleavage to generate a Ce III complex and a benzyloxy radical. Although the exact catalytic cycle of our reaction remains to be elucidated, we propose a plausible reaction mechanism based on our observations and known literature precedents (Figure 1B) [57,59,[66][67][68][69]. Under aerobic conditions the catalytic Ce III (OBn)L n species I (in situ derived by the reaction of CeCl 3 (Ce III L n ) with the substrate benzyl alcohol, BnOH) could be oxidized to L n Ce IV -OBn complex II [67][68][69].…”

Mechanistic Insights into the Formation of δ‐Lactones by Cerium‐Catalyzed Aerobic Coupling of β‐Oxoesters with Enol Acetates

“…Recently, we have discovered the formation of δ‐lactones 4 with an 1,4‐dicarbonyl moiety in the side chain when acetophenone derived enol ethers like compound 2 a , were submitted to this aerobic coupling reaction with β‐oxoesters 1 [10] . Species 5 – 7 have meanwhile been identified as intermediates of the lactone formation [11] . Compound 5 a is the result of a coupling reaction of oxoester 1 a , enol acetate 2 a , and dioxygen according to a radical chain reaction.…”

“…In contrast to the BVO, where the higher substituted residue migrates, the less substituted alkyl residue undergoes the 1,2‐shift in this case. Intermediate species 6 a and 7 a were investigated by reaction kinetics and computational methods [11] …”

The First Total Synthesis of Racemic Chebulic Acid

“…The product 12 was obtained in 66 % yield as a mixture of again two diastereoisomers ( dr 2 : 1). Since the oxidation is assumed to proceed via a planar radical species, [11c,d] neither diastereomeric ratio nor the relative configuration of compounds 10 and 12 must necessarily correlate. As a byproduct, γ‐lactone 11 was separated and isolated in 23 % yield as a single diastereoisomer which is obviously the result of intramolecular transesterification under the reaction conditions.…”