Sustainable, Oxidative, and Metal‐Free Annulation

Abstract

Annulation has received steadily growing interest in the interplay with the increasing emphasis towards selective C-H bond functionalization reactions. Metal-free oxidative annulation through functionalization of inert and abundant C-H bonds offers great improvements in terms of atom- and step-economics as well as reduced waste production under mild reaction conditions. Annulation is considered to be a highly efficient strategy for the construction of cyclic molecules because at least two new bonds are formed within a single reaction step. The combination of annulation and direct C-H bond functionalization allows the efficient and straightforward synthesis of carbo- and heterocyclic molecules using simple and non-prefunctionalized precursors. This Concept highlights novel strategies and recent breakthroughs for metal-free annulation through C-H bond functionalization giving access to a variety of important structural motifs.

I(III)-Catalyzed Oxidative Cyclization–Migration Tandem Reactions of Unactivated Anilines

“…At the conclusion of our study, we were curious if catalysis could be achieved by pairing iodobenzene with a superstoichiometric oxidant. Oxidative catalytic processes using an iodine catalyst have emerged recently as a powerful way to create new bonds through the dearomatization of electron-rich arenes. , While phenols and aromatic ethers are common substrates, the development of I­(III)-catalyzed oxidative methods of anilines remains nascent and requires a strong electron-withdrawing group on nitrogen for C–N bond formation . In 2011, Antonchick and co-workers reported that biaryl acetimides could be transformed into N -acetyl carbazoles using a diiodobiaryl catalyst and acetic peroxide as the oxidant (Scheme ).…”

“…The ubiquitous nature of C–N bonds in nonplanar N -heterocycles and materials continues to spur the development of efficient processes that generate electrophilic nitrogen catalytic intermediates to trigger C–N bond formation. , While this intermediate can be accessed by oxidation, most methods require the presence of a strong electron-withdrawing N -substituent for a successful reaction outcome . In contrast, catalytic reactions that construct C–NAr bonds employ an aryl azide or nitroarene as the N atom source require heat or superstoichiometric quantities of reductant to access the electrophilic N -aryl nitrogen intermediate. , Oxidative methods that generate the electrophilic N -aryl intermediate are less common and require an N -electron-withdrawing substituent on the aniline. We discovered that electrophilic N -aryl nitrenoids could be generated from I­(III)-mediated oxidation of unactivated 2-substituted anilines and trapped to afford benzazepinones or 3 H -indoles .…”

Oxidation of Nonactivated Anilines to Generate N-Aryl Nitrenoids

“…While many elegant studies have advanced this approach to oxidative nitrene transfer reactions for use in complex molecule synthesis, all of these methods require a strong electron-withdrawing group on nitrogen to access productive C–N bond-forming reactivity . Despite the ubiquitous nature of the N -aryl group in synthetic targets and established practical processes for the oxidation of phenols, oxidative methods that form N -aryl nitrenes from anilines to produce C–NAr bonds have lagged behind those of sulfonamides and carbamates . Current methods require the presence of a strong electron-withdrawing group on the nitrogen and have been limited to the formation of planar N -heterocycles (Scheme B). ,, For example, Antonchick and co-workers reported that carbazoles could be formed from the oxidation of biarylamines 7 only if an N -acetyl group was present; no N -heterocycle formation was observed in its absence or if it was replaced with a benzyl group .…”

Metal-Free C–O Bond Functionalization: Catalytic Intramolecular and Intermolecular Benzylation of Arenes

“…At present, the application in C–O bond activation is limited to protecting group removal . Because of our ongoing interest in metal-free reaction methodologies, we aimed to target the catalytic functionalization of C–O bonds using nitrosonium salts. Herein, we report the metal-free intramolecular rearrangement of benzyl phenyl ethers using low loading of catalyst, which enabled a intermolecular and catalytic synthesis of various diarylmethanes from alcohols and arenes, producing water as the stoichiometric byproduct (Figure C).…”