Cyclic Hypervalent Iodine Reagents: Enabling Tools for Bond Disconnection via Reactivity Umpolung

Abstract

Conspectus The efficient synthesis of organic compounds is an important field of research, which sets the basis for numerous applications in medicine or materials science. Based on the polarity induced by functional groups, logical bond disconnections can be deduced for the elaboration of organic compounds. Nevertheless, this classical approach makes synthesis rigid, as not all bond disconnections are possible. The concept of Umpolung has been therefore introduced: by inverting the normal polarity of functional groups, new disconnections become possible. Among the tools for achieving Umpolung, hypervalent iodine reagents occupy a privileged position. The electrophilicity of the iodine atom and the reactivity of the hypervalent bond allow access to electrophilic synthons starting from nucleophiles. Nevertheless, some classes of hypervalent iodine reagents can be too unstable for many applications, in particular involving metal catalysis. In this context, cyclic hypervalent iodine reagents, especially benziodoxolones (BXs), have been known for a long time to be more stable than their acyclic counterparts, yet their synthetic potential had not been fully exploited. In this Account, we report our efforts since 2008 on the use of BX reagents in the development of new transformations in organic synthesis, which showed for the first time their versatility as synthetic tools. Our work started with electrophilic alkynylation, as alkynes are one of the most important functional groups in organic chemistry, but are usually introduced as nucleophiles. We used ethynylbenziodoxolones (EBXs) in the direct alkynylation of nucleophiles, such as keto esters, thiols, or phosphines. The reagents could then be applied to the gold- and palladium-catalyzed alkynylation of C–H bonds on (hetero)­arenes, leading to a more efficient alternative to the Sonogashira reaction. More complex reactions were then developed with formations of several bonds in a single transformation. Gold- and platinum-catalyzed cyclization/alkynylation domino processes gave access to new types of alkynylated heterocycles. Multifunctionalization of olefins became possible through intramolecular oxy- and amino-alkynylations. (Enantioselective) copper-catalyzed oxy-alkynylation of diazo compounds led to stereocenters with perfect atom economy. Finally, EBXs were also used for the alkynylation of radicals generated under photoredox conditions. Since 2013, we then extended the use of BX reagents to other transformations. Azidobenziodoxol­(on)­ess (ABXs) were used in the azidation of keto esters, enol silanes, and styrenes. New more stable derivatives were introduced. Cyanobenziodoxolones (CBXs) enabled the cyanation of stabilized enolates, thiols, and radicals. Finally, new BX reagents were developed for the Umpolung of indoles and pyrroles. They could be used in metal-catalyzed directed C–H functionalizations, as well as in Lewis acid mediated oxidative coupling to give functionalized bi­(hetero)­arenes. In the past decade, our group and others have shown that BX reag...

Recent Synthetic Applications of the Hypervalent Iodine(III) Reagents in Visible-Light-Induced Photoredox Catalysis

“…The special structural features and unparalleled reactivities of HIRs lie in their unique 3-center-4-electron (3c-4e) bonds (L—I(III) —X), which are highly polarized and are longer and weaker than classical covalent bonds (Zhdankin, 2013 ; Yoshimura and Zhdankin, 2016 ; Jia and Chen, 2018 ). Generally, HIRs offer multiple advantages for synthetic organic chemistry: (i) mild and highly chemoselective oxidizing properties; (ii) benign environmental character; (iii) commercial availability; and (iiii) convenient structural modification (Brand et al, 2011 ; Zhdankin, 2013 ; Li Y. et al, 2016 ; Yoshimura and Zhdankin, 2016 ; Hari et al, 2018 ). These advantages of HIRs give synthetic chemists the opportunities to design and access novel and more challenging reactions.…”

An umpolung strategy to react catalytic enols with nucleophiles

“…For the synthesis of α-functionalized ketones with iodine(III) compounds, several reagents have been successfully used. These include Koser's reagent 23 , (diacetoxyiodo)benzene (PIDA) 24 , p-iodotoluene difluoride 25 , and benzioxol(on)es (BX) 26 . When acyclic I(III) reagents are used, the nucleophile can be either an external nucleophile or a ligand of the I(III) center.…”

2-Iodoxybenzoic acid ditriflate: the most powerful hypervalent iodine(v) oxidant

“…In recent years, the interest in synthetic applications of hypervalent iodine compounds as versatile oxidizing reagents and catalysts has experienced an explosive growth. [1][2][3][4][5][6][7][8][9] Hypervalent iodine(V) reagents represent a particularly important class of oxidants extensively employed in organic synthesis. 2-Iodoxybenzoic acid (IBX, structure 1 in Fig 1) and the product of its acetylation Dess-Martin periodinane (DMP, 2) have become the most common oxidizing reagents used for selective oxidation of alcohols to carbonyl compounds and other synthetically useful oxidative transformations.…”