Application of Electrochemically Generated Hypervalent Iodine Oxidant to Natural Products Synthesis

Abstract

Hypervalent iodine oxidants have been widely applied in organic reactions due to their low toxicity, ready availability, and ease of handling. We produced an oxidant, [phenyliodine(III)bis(trifluoroethoxide)] (PIFE) by anodic oxidation of iodobenzene, which possesses comparable or superior properties to those of commercially available congeners, such as [phenyliodine(III)bis(trifluoroacetate)] (PIFA) and [phenyliodine(III)diacetate] (PIDA). The availability of PIFE was demonstrated by construction of several nitrogen-containing molecular skeletons; construction of quinolinone derivatives by PIFE occurred smoothly in moderate yield. In addition, the carbazole derivatives were synthesized in higher yields than with use of PIFA. Application of this methodology enabled synthesis of the bioactive tetrahydropyrroloiminoquinone-, carbazole-, and pyrroloindole-class natural products, including makaluvamines, damirones, glycozoline, debromofrustraminol B, and CPC-1.

Hypervalent Iodine Reagents by Anodic Oxidation: A Powerful Green Synthesis

“…The Nishiyama group developed the electrochemically generated hypervalent iodine reagent [bis(trifluoroethoxy)iodo]benzene 30 (Figure ) as an alternative to the commercially available reagents such as (diacetoxyiodo)benzene. The reactivity of 30 is comparable and sometimes superior to (diacetoxyiodo)benzene, which is illustrated by its successful applications in the construction of a variety of oxygen and nitrogen‐containing scaffolds, natural products and the oxidation of the naturally occurring xanthone derivatives (Mangostins) …”

Recent advances in the electrochemical construction of heterocycles

“…As a part of their efforts in the total synthesis of several natural products, Nishiyama and co-workers developed an electrochemical method for the construction of N -heterocyclic cores (see examples depicted in Scheme 14 and Scheme 15) [58–60]. PhI(OCH 2 CF 3 ) 2 was generated anodically from iodobenzene in a solution of LiClO 4 in 2,2,2-trifluoroethanol and served as reagent for the oxidative intramolecular coupling of phenyl rings with amide or carbamate groups.…”

“…With control experiments the authors demonstrated that this in situ generated reagent works more efficiently in such cyclizations than the more frequently used PIFA reagent. For instance, cyclization of biaryl 35 to carbazole 36 was achieved using this indirect electrochemical approach (Scheme 14) [59–60]. The transformation represents the key-step of the synthesis of glycozoline 37 , an antifungal and antibacterial agent.…”

“…The transformation represents the key-step of the synthesis of glycozoline 37 , an antifungal and antibacterial agent. Analogously, 38 was converted to 39 as a part of the multistep synthesis of two different tetrahydropyrroloiminoquinone alkaloids 40 and 41 (Scheme 15) [58,60]. …”

Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron‐Rich Substrates

“…[21] The electrochemical generation of many hypervalent l 3iodane species from aryl-iodides is known. [22] Difluoro l 3iodanes (1) has been comparatively less explored, [23] with Waldvogel recently reporting the only example in the presence of alkenes, [23e] which are liable to preferentially oxidise. A number of additional problems are reported to occur when 1 is generated at an electrode, [24] which include dimerization, benzylic fluorination and the formation of "many other complicated products".…”