Self-assembled ion-pair organocatalysis – asymmetric Baeyer–Villiger oxidation mediated by flavinium–cinchona alkaloid dimer

Abstract

An ion-pair catalyst generated by assembly of a chiral flavinium and a cinchona alkaloid dimer for use in asymmetric Baeyer-Villiger oxidation is presented. Ion-pair formation is essential for enhancing the catalytic activity and stereoselectivity. The catalyst is applicable to structurally diverse 3-substituted cyclobutanones, providing good to excellent enantioselectivities (up to 98 : 2 e.r.). This study provides the first example of self-assembly of a flavin derivative and a base to form a chiral reaction site that enables a highly stereoselective reaction to occur.

Phosphothreonine (pThr)-Based Multifunctional Peptide Catalysis for Asymmetric Baeyer–Villiger Oxidations of Cyclobutanones

“…Preliminary studies in our laboratory on pThr-based peptide catalysts for the enantioselective BV oxidation commenced with 3-phenylcyclobutanone ( 4a ) and peptide catalyst P2 (Scheme 2). Employing similarly established reaction conditions 17b , the Baeyer–Villiger oxidation of 4a proceeded to give 5a with high conversion, albeit with low enantioselectivity (55:45 er). With 4b , bearing a prochiral quaternary carbon, γ-butyrolactone 5b was obtained in 95% conversion with a slight increase in enantioselectivity (57:43 er).…”

“…Notably, P18 provided higher enantioselectivity than commercially available BINOL derived CPA, ( R )-TRIP 1b (64:36 er), and comparable selectivities (81:19 er) to those previously reported. 17b…”

“…Discovered in 1899, the Baeyer–Villiger (BV) reaction 15 remains an indispensable tool for accessing chiral esters and lactones from the corresponding ketone precursors through the use of enzymes, 16 organocatalysts, 17 and transition metal complexes. 18 Inspired by the pioneering work of Ding and co-workers on CPA-catalyzed BV oxidation 17b , we endeavored to learn whether pThr-based CPAs could facilitate oxidation chemistry with comparable or complementary selectivities and achieve a benchmark for peptide catalysts for the diversification of more complex substrates (Figure 1d). The enantioselective BV reaction of symmetrical, cyclic ketones is particularly appealing for elucidating catalyst control given the mechanistic ramifications.…”

Advances in Chemocatalytic Asymmetric Baeyer–Villiger Oxidations

“…In contrast to the above methods using a single chiral catalyst, Yamamoto and co‐workers described that the in situ assembly of a chiral flavinium 74 and a dimeric Cinchona alkaloid (DHQ) 2 PHAL could deliver an ion‐pair catalyst for the enantioselective B‐V reaction (Scheme ) . Initially, the π–π and ionic interactions between flavinium 74 and (DHQ) 2 PHAL could help to form an artificial chiral reaction site; then the hydrogen peroxide attacks the iminium of 74 to form a hydroperoxy species, which further adds to the less‐hindered side of the carbonyl group to form a Criegee intermediate that undergoes rearrangement to give the lactones.…”

Enantioselektive Desymmetrisierung von Cyclobutanonen: Eine Schnellstraße zu molekularer Komplexität

“…[30,31] Yamamoto et al entwickelten die enantioselektive Bildung des Carbamats 30 und des aliphatischen Lactons 31 durch eine synergistische Anordnung von Flavin 29 und (DHQ) 2 PHAL (Schema 6D). [32,33] Der Mechanismus ist dem Enzymprozess ähnlich, wobei eine Addition von Wasserstoffperoxid an Flavin der Addition an Cyclobutanon 1 vorausgeht. [34] Kurze [37] Zunächst strebten die Autoren eine a-Hydroxylierung am Vierring an, wie sie bei verwandten organokatalytischen Reaktionen mit Ketonen und Aldehyden zu beobachten ist.…”