Manganese‐Mediated Homolytic Aromatic Substitution with Phosphinylidenes

Carbon‐phosphorus (C−P) bond‐forming reactions via homolytic aromatic substitution (HAS) of non‐functionalized substrates with phosphinylidene P(O)H compounds is becoming a useful synthetic tool for the preparation of aryl and heteroaryl phosphonates, phosphinates, and phosphine oxides. This review specifically covers recent work using manganese‐mediated free radical processes. Several research groups employ expensive Mn(OAc)₃, whereas our own contributions focus on the novel and inexpensive Mn(OAc)₂/MnO₂ system.     

Photoredox Catalyzed Dealkylative Aromatic Halogen Substitution with Tertiary Amines

A reaction of aromatic halides bearing electron-withdrawing groups with tertiary amines in the presence of an iridium catalyst under blue light irradiation is described. Products of the aromatic substitution of the halide by the dialkylamino fragment are obtained. The interaction of aryl radicals with tertiary amines to generate zwitterionic radical species is believed to be the key factor responsible for the reaction efficiency.     

Reaction Mechanism of 3,4‐Dinitrofuroxan Formation from Glyoxime: Dehydrogenation and Cyclization of Oxime

The reaction pathway of the formation of 3,4‐dinitrofuroxan from glyoxime is theoretically investigated under experimental conditions with 25 % nitric acid and dinitrogentetroxide reagents to clarify the mechanism of formation of a furoxan ring by glyoxime. The geometric configurations of minima and transition‐state species are optimized at the (U)B3LYP/6‐311++G** level. The CCSD(T) and CASSCF(10e,8o)/CASSCF(9e,8o) single‐point energy corrections at the same level are performed on top of the optimized geometries. A subsequent dynamic correlation by using NEVPT2/6‐311++G**‐level single‐point energy calculations based on the CASSCF results is also performed to obtain accurate energy values. The formation reaction is analyzed from two processes: glyoxime nitration and 3,4‐dinitroglyoxime (nitration product) oxidative cyclization. Calculation results indicate that the electrophilic substitution of nitronium ions from the protonated HNO₃ and the abstraction of hydrogen ions by HNO₃ molecules are requisites of glyoxime nitration. The formation of a furoxan ring from 3,4‐dinitroglyoxime involves two possible mechanisms: 1) oxydehydrogenation by NO₂ molecules and the subsequent torsion of NO radical groups to form a ring and 2) the alternation of dehydrogenation and cyclization. The intermediates and transition states in both routes exhibit monoradical and diradical characteristics. Singlet and triplet reactions are considered for the diradical species. Results show that the singlet reaction mechanism is more favorable for cyclization than the triplet reaction. The formation of a furoxan ring from oxime is in accordance with the stepwise intermolecular dehydrogenation and intramolecular torsion to the ring.     

Metal‐free Synthesis of Aryl Amines: Beyond Nucleophilic Aromatic Substitution

A mild and metal‐free approach to C?N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ipso‐substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal‐free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal‐free C?N coupling reactions.     

Iron‐Catalyzed Allylic Amination Directly from Allylic Alcohols

Allylic amination, directly from alcohols, has been demonstrated without any Lewis acid activators using an efficient and regiospecific molecular iron catalyst. Various amines and alcohols were employed and the reaction proceeded through the oxidation/reduction (redox) pathway. A direct one‐step synthesis of common drugs, such as cinnarizine and nafetifine, was exhibited from cinnamyl alcohol that produced water as side product.     

On the Radical Nature of Iron‐Catalyzed Cross‐Coupling Reactions

The radical nature of iron‐catalyzed cross‐coupling between Grignard reagents and alkyl halides has been studied by using a combination of competitive kinetic experiments and DFT calculations. In contrast to the corresponding coupling with aryl halides, which commences through a classical two‐electron oxidative addition/reductive elimination sequence, the presented data suggest that alkyl halides react through an atom‐transfer‐initiated radical pathway. Furthermore, a general iodine‐based quenching methodology was developed to enable the determination of highly accurate concentrations of Grignard reagents, a capability that facilitates and increases the information output of kinetic investigations based on these substrates.     

Iron‐Catalyzed Synthesis of the Hexahydrocyclopenta[c]furan Core and Concise Total Synthesis of Polyflavanostilbene B

The first synthesis of polyflavanostilbene B ( 1 ), which has seven contiguous stereocenters including two quaternary carbon centers, from abundant polymeric (?)‐epicatechin gallate on a gram scale in three steps without the use of protecting groups is reported. The key transformations of this strategy include a regioselective and stereoselective substitution of resveratrol to give the 4‐derivative of (?)‐epicatechin 3‐gallate and an iron‐catalyzed cyclization reaction. The possible radical cyclization mechanism in the formation of the hexahydrocyclopenta[c]furan core is also discussed.     

Iron‐Catalyzed Direct Diazidation for a Broad Range of Olefins

Reported herein is a new iron‐catalyzed diastereoselective olefin diazidation reaction which occurs at room temperature (1–5 mol % of catalysts and d.r. values of up to >20:1). This method tolerates a broad range of both unfunctionalized and highly functionalized olefins, including those that are incompatible with existing methods. It also provides a convenient approach to vicinal primary diamines as well as other synthetically valuable nitrogen‐containing building blocks which are difficult to obtain with alternative methods. Preliminary mechanistic studies suggest that the reaction may proceed through a new mechanistic pathway in which both Lewis acid activation and iron‐enabled redox‐catalysis are crucial for selective azido‐group transfer.     

Base‐Controlled Selectivity in the Synthesis of Linear and Angular Fused Quinazolinones by a Palladium‐Catalyzed Carbonylation/Nucleophilic Aromatic Substitution Sequence

A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium‐catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et₃N promotes the preferential formation of angular products. Interestingly, a light‐induced 4+4 reaction of the product was also observed.     

Iron(II)‐Catalyzed Direct Cyanation of Arenes with Aryl(cyano)iodonium Triflates

A direct oxidative cyanation of arenes under Fe^II catalysis with 3,5‐di(trifluoromethyl)phenyl(cyano)iodonium triflate (DFCT) as the cyanating agent has been developed. The reaction is applicable to wide range of aromatic substrates, including polycyclic structures and heteroaromatic compounds.     

Transition‐Metal‐Free Intramolecular Carbene Aromatic Substitution/Büchner Reaction: Synthesis of Fluorenes and [6,5,7]Benzo‐fused Rings

Intramolecular aromatic substitution and Büchner reaction have been established as powerful methods for the construction of polycyclic compounds. These reactions are traditionally catalyzed by Rh^II catalysts with α‐diazocarbonyl compounds as the substrates. Herein a transition‐metal‐free intramolecular aromatic substitution/Büchner reaction is presented. These reactions use readily available N‐tosylhydrazones as the diazo compound precursors and show wide substrate scope.     

Highly Diastereo‐ and Enantioselective Silver‐Catalyzed Double [3+2] Cyclization of α‐Imino Esters with Isocyanoacetate

Presented herein is a new complexity‐generating method in which both functionalities of α‐imino esters undergo stereoselective cyclization with isocyanoacetates to produce directly linked oxazole‐imidazolines, which can be transformed into highly functionalized α,β‐diamino esters and imidazolinium salts in high diastereo‐ and enantiopurity.     

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

Palladium‐catalyzed cascade cyclization reactions have witnessed significant improvements in recent years. Among them, palladium‐catalyzed cascade cyclization/alkynylation are especially attractive, which can assemble structurally diverse monocyclic, bicyclic, fused polycyclic, and spirocyclic skeletons with excellent chemoselectivities. In this Minireview, palladium‐catalyzed cascade cyclization/alkynylation have been summarized and discussed in detail with focus on oxypalladation and aminopalladation‐initiated cascade cyclization, intramolecular Heck‐type cascade cyclization, carbocyclizations, cascade cyclizations, and other types of cascade cyclization reactions. Some significant and representative synthetic methodologies and their synthetic applications and reaction mechanisms have also been described.