Hypervalent Iodine(III)‐Catalysed Enantioselective α‐Acetoxylation of Ketones

Abstract

An enantioselective catalytic synthesis of α‐acetoxylated ketones through I(I)/I(III) catalysis using a resorcinol/lactamide‐based chiral iodoarene is reported. Catalyst turnover by in situ generation of the active iodine(III) derivative is achieved by oxidation with mCPBA in the presence of acetic acid. The prior transformation of ketones to easily accessible acetyl enol ethers is beneficial and yields up to 97 % with enantioselectivities up to 88 % ee are obtained using only low catalyst loadings of only 5 mol % under mild reaction conditions.

C−N Axial Chiral Hypervalent Iodine Reagents: Catalytic Stereoselective α‐Oxytosylation of Ketones

“…Herein, we report a simple synthesis of a small library of novel C−N axial chiral iodoarenes, starting from commercially available aniline derivatives and investigate their potential as chiral organocatalysts using the extensively studied—yet challenging—hypervalent iodine mediated stereoselective α‐oxytosylation of ketones as a model reaction [5c–d, 14] …”

Reactions promoted by hypervalent iodine reagents and boron Lewis acids

“…Wirth and coworkers investigated the enantioselective synthesis of α-acetoxylated ketones using catalytic amounts of chiral λ 3 -iodanes. 55 The λ 3 -iodanes were generated in situ from the reaction of chiral λ 3 -iodanes 48 and an oxidising agent in the presence of acetic acid. Lewis acidic BF 3 •OEt 2 was employed to activate the hypervalent λ 3 -iodanes and then subsequent reaction with the enol ether 49 afforded an intermediate in which the activated λ 3 -iodane was attached to the α-carbon of the carbonyl functional group.…”

Deciphering the Keys for High Enantioselectivity in Hypervalent Iodine-Catalyzed 1,2-Difunctionalization: Improved Synthesis of Ishihara–Muñiz Precatalysts

“…The principal attribute for iodine reagents gaining this status is their high reactivity and reliability, combined with good site selectivity and broad applicability in many transformations within organic synthesis. , On the contrary, the main reasons that aryliodines have spread in the chemistry of vicinal transformations are a consequence of their facile and adaptable synthesis, which allows for the modular construction of fit-for-purpose precatalysts (see Figure ). Departing from the aryliodine core, many different precatalysts can be synthesized through direct paths, creating a wide variety of precatalysts with different key structural features shown to make a large impact upon a given reaction’s yield and ee. , The oxidative control required over a given reaction substrate has been achieved, and thus iodine­(I/III) catalysis are seen today as the natural heir of the original iodine­(III)-related chemistry. , Furthermore, both in vitro and experimental studies have shined light on the mechanisms of the developed reactions, creating a deeper understanding and providing a base on which the progress relies. − Four main reaction types have been particularly explored (Figure ): oxygenation, oxidative dearomatization, difluorination, and diamination. All of them share similar reaction mechanisms, on the basis of the great leaving group capacity of the aryliodonio moiety, in turn provoked by the electronic configuration and electron disposition within the reactive I­(III) center. , …”

“…Departing from the aryliodine core, many different precatalysts can be synthesized through direct paths, creating a wide variety of precatalysts with different key structural features shown to make a large impact upon a given reaction's yield and ee. 18,19 The oxidative control required over a given reaction substrate has been achieved, and thus iodine(I/III) catalysis are seen today as the natural heir of the original iodine(III)-related chemistry. 20,21 Furthermore, both in vitro and experimental studies have shined light on the mechanisms of the developed reactions, creating a deeper understanding and providing a base on which the progress relies.…”

“…20 These facts severely hamper the use of large-scale I(I/III)-catalyzed transformations at the industrial level, or even for academic purposes when large screenings must be performed. 18 Recently, Ishihara brought focus to the scalability of his second-generation precatalyst and the dearomatization reaction it mediates. 29,30 Nevertheless, a unified, general, and scalable synthesis for the first generation of these catalysts helping to generalize the use of iodine(I/III) catalysis among the scientific community has been long overdue.…”