Acyl Fluorides in Late‐Transition‐Metal Catalysis

In this Review, we summarize the current state of the art in late‐transition‐metal‐catalyzed reactions of acyl fluorides, covering both their synthesis and further transformations. In organic reactions, the relationship between stability and reactivity of the starting substrates is usually characterized by a trade‐off. Yet, acyl fluorides display a very good balance between these properties, which is mostly due to their moderate electrophilicity. Thus, acyl fluorides (RCOF) can be used as versatile building blocks in transition‐metal‐catalyzed reactions, for example, as an “RCO” source in acyl coupling reactions, as an “R” source in decarbonylative coupling reactions, and as an “F” source in fluorination reactions. Starting from the cleavage of the acyl C?F bond in acyl fluorides, various transformations are accessible, including C?C, C?H, C?B, and C?F bond‐forming reactions that are catalyzed by transition‐metal catalysts that contain the Group 9–11 metals Co, Rh, Ir, Ni, Pd, or Cu.     

Mechanistic Study on Ligand‐Controlled Cobalt‐Catalyzed Regioselectivity‐Switchable Hydroarylation of Styrenes

Density functional theory (DFT) calculations have been performed to study the mechanism of the recently reported Co‐catalyzed ligand‐controlled hydroarylation of styrenes as a means of preparing 1,1‐ or 1,2‐diarylalkanes. The present study corroborates the previously proposed three‐step mechanism, comprising C? H activation (C? H oxidative addition), styrene insertion, and reductive elimination. In the C? H activation and reductive elimination steps, our calculations suggest that styrene does not coordinate to the Co center. In the insertion step, styrene is inserted into the Co? H bond rather than the Co? C bond. Furthermore, the rate‐ and regiodetermining step is found to be C? C reductive elimination. It is significant that the regioselectivity observed experimentally has been successfully reproduced by our calculations. More importantly, in analyzing the origin of the ligand‐controlled regioselectivity, we have found that the steric effects of different ligands mainly determine the observed regioselectivity. Both the shape (i.e., “umbrella‐up” or “umbrella‐down”) and bulkiness of the ligand contribute to the steric effect.     

Oxidative Enantioselective α‐Fluorination of Aliphatic Aldehydes Enabled by N‐Heterocyclic Carbene Catalysis

Described is the first study on oxidative enantioselective α‐fluorination of simple aliphatic aldehydes enabled by N‐heterocyclic carbene catalysis. N‐fluorobis(phenyl)sulfonimide serves as a an oxidant and as an “F” source. The C? F bond formation occurs directly at the α position of simple aliphatic aldehydes, thus overcoming nontrivial challenges, such as competitive difluorination and nonfluorination, and proceeds with high to excellent enantioselectivities.     

“Dumbbell”‐ and “Clackers”‐Shaped Dimeric Derivatives of Monocarba‐closo‐dodecaborate

We designed, synthesized, and characterized two types of dimeric forms of monocarba‐closo‐dodecaborate, namely, a “dumbbell”‐shaped dianion having a C?C bond and a “clackers”‐shaped monoanion having an iodonium linker. The unique architectures of these anionic molecules were established by X‐ray analysis. Spectroscopic analysis, DFT calculations, and reactivity experiments revealed high anionic and chemical stability of both anions, which are crucial properties for weakly coordinating anions.     

Encapsulating Au‐Fe3O4 Nanodots into AIE‐active Supramolecular Assemblies: Ambient Visible‐light Harvesting “Dip‐Strip” Photocatalyst for C−C/C−N Bond Formation Reactions

The present study demonstrates the development of a supramolecular porous ensemble consisting of hetero‐oligophenylene derivative 6 and Au‐Fe₃O₄ nanodots. Supramolecular assemblies of AIE‐active hetero‐oligophenylene derivative 6 served as reactors for the generation of Au‐Fe₃O₄ nanodots. The as prepared supramolecular ensemble functioned as an efficient recyclable photocatalytic system for C(sp²)?H bond activation of anilines for the construction of quinoline carboxylates. Interestingly, the “dip catalyst” prepared by depositing PTh‐co‐PANI‐6: Au‐Fe₃O₄ nanodots on a filter paper served as a recyclable strip (up to 10 cycles) for C?C/C?N bond formation reaction.     

Through‐Space 1,4‐Palladium Migration and 1,2‐Aryl Shift: Direct Access to Dibenzo[a,c]carbazoles through a Triple CH Functionalization Cascade

A palladium‐catalyzed expeditious synthesis of dibenzofused carbazoles from readily available 2‐arylindoles and diaryliodonium salts is reported. Interestingly, after the electrophilic C3 palladation of indole, an unexpected “through‐space” 1,4‐palladium migration to the 2‐aryl moiety, by remote C?H bond activation followed by C?H arylation with diaryliodonium salt, and an unprecedented 1,2‐aryl shift take place. Finally, an intramolecular cross‐dehydrogenative coupling (CDC) at the C2 position affords dibenzo[a,c]carbazoles in high yields. Remarkably, the present migratory annulation occurs through three C?H bond activation one C?C bond cleavage, and the simultaneous construction of three new C?C bonds in a single operation.     

Carbonylative C−C Bond Activation of Electron‐Poor Cyclopropanes: Rhodium‐Catalyzed (3+1+2) Cycloadditions of Cyclopropylamides

Rh‐catalyzed carbonylative C?C bond activation of cyclopropylamides generates configurationally stable rhodacyclopentanones that engage tethered alkenes in (3+1+2) cycloadditions. These studies provide the first examples of multicomponent cycloadditions that proceed through C?C bond activation of “simple” electron poor cyclopropanes.     

Hydrogen‐Bond‐Mediated Asymmetric Catalysis

The utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric organocatalysis. Significant advances have been made in the recent past in this emerging field. Due to space constraints, this Focus Review summarizes only the key aspects with an emphasis on catalysis based on chiral ureas and thioureas, diols, and phosphoric acids. The examples provided neatly demonstrate that chiral ureas and thioureas, diols, and phosphoric acids display effective and unique activation modes of catalysis for a broad spectrum of asymmetric organic transformations, including single‐step and multiple‐step cascade reactions. These functionalities, which have the ability to afford efficient H‐bond activation of electrophiles including C?O, C?N, aziridines, and epoxides, have established their status as “privileged” functional groups in the design of organocatalysts.     

Rollover‐Assisted C(sp2)C(sp3) Bond Formation

Rollover cyclometalation involves bidentate heterocyclic donors, unusually acting as cyclometalated ligands. The resulting products, possessing a free donor atom, react differently from the classical cyclometalated complexes. Taking advantage of a “rollover”/“retro‐rollover” reaction sequence, a succession of oxidative addition and reductive elimination in a series of platinum(II) complexes [Pt(N,C)(Me)(PR₃)] resulted in a rare C(sp²)?C(sp³) bond formation to give the bidentate nitrogen ligands 3‐methyl‐2,2′‐bipyridine, 3,6‐dimethyl‐2,2′‐bipyridine, and 3‐methyl‐2‐(2′‐pyridyl)‐quinoline, which were isolated and characterized. The nature of the phosphane PR₃ is essential to the outcome of the reaction. This route constitutes a new method for the activation and functionalization of C?H bond in the C(3) position of bidentate heterocyclic compounds, a position usually difficult to functionalize.     

One‐pot Annulation for Biaryl‐fused Monocarba‐closo‐dodecaborate through Aromatic B−H Bond Disconnection

We have developed a one‐pot annulation reaction of monocarba‐closo‐dodecaborate with cyclic diaryliodonium salts to afford biaryl‐fused derivatives. Aryl functionalities are introduced at both the 1‐carbon and unreactive ortho‐boron vertices of the “σ‐aromatic” carborane cage without the need for pre‐functionalization. DFT calculations revealed that the palladium‐catalyzed C?B bond‐formation step in this process proceeds through a concerted metalation–deprotonation (CMD)‐type pathway for the B?H bond disconnection on the aromatic cage, though such bonds are generally regarded as hydridic.     

Transition‐Metal‐Free Activation of Amides by N−C Bond Cleavage

The amide bond N?C activation represents a powerful strategy in organic synthesis to functionalize the historically inert amide linkage. This personal account highlights recent remarkable advances in transition‐metal‐free activation of amides by N?C bond cleavage, focusing on both (1) mechanistic aspects of ground‐state‐destabilization of the amide bond enabling formation of tetrahedral intermediates directly from amides with unprecedented selectivity, and (2) synthetic utility of the developed transformations. Direct nucleophilic addition to amides enables a myriad of powerful methods for the formation of C?C, C?N, C?O and C?S bonds, providing a straightforward and more synthetically useful alternative to acyl‐metals.     

Non‐coordinating‐Anion‐Directed Reversal of Activation Site: Selective C−H Bond Activation of N‐Aryl Rings

An Rh‐catalyzed selective C?H bond activation of diaryl‐substituted anilides is described. In an attempt to achieve C?H activation of C‐aryl rings, we unexpectedly obtained an N‐aryl ring product under non‐coordinating anion conditions, whereas the C‐aryl ring product was obtained in the absence of a non‐coordinating anion. This methodology has proved to be an excellent means of tuning and adjusting selective C?H bond activation of C‐aryl and N‐aryl rings. The approach has been rationalized by mechanistic studies and theoretical calculations. In addition, it has been found and verified that the catalytic activity of the rhodium catalyst is obviously improved by non‐coordinating anions, which provides an efficient strategy for obtaining a highly chemoselective catalyst. Mechanistic experiments also unequivocally ruled out the possibility of a so‐called “silver effect” in this transformation involving silver.     

Nickel‐Catalyzed Allylic Alkylation with Diarylmethane Pronucleophiles: Reaction Development and Mechanistic Insights

Palladium‐catalyzed allylic substitution reactions are among the most efficient methods to construct C?C bonds between sp³‐hybridized carbon atoms. In contrast, much less work has been done with nickel catalysts, perhaps because of the different mechanisms of the allylic substitution reactions. Palladium catalysts generally undergo substitution by a “soft”‐nucleophile pathway, wherein the nucleophile attacks the allyl group externally. Nickel catalysts are usually paired with “hard” nucleophiles, which attack the metal before C?C bond formation. Introduced herein is a rare nickel‐based catalyst which promotes substitution with diarylmethane pronucleophiles by the soft‐nucleophile pathway. Preliminary studies on the asymmetric allylic alkylation are promising.     

PAd2‐DalPhos Enables the Nickel‐Catalyzed C−N Cross‐Coupling of Primary Heteroarylamines and (Hetero)aryl Chlorides

Base‐metal catalysts capable of enabling the assembly of heteroatom‐dense molecules by cross‐coupling of primary heteroarylamines and (hetero)aryl chlorides, while sought‐after given the ubiquity of unsymmetrical di(hetero)arylamino fragments in pharmacophores, are unknown. Herein, we disclose the new “double cage” bisphosphine PAd2‐DalPhos ( L2 ). The derived air‐stable Ni^II pre‐catalyst C2 functions well at low loadings in challenging test C?N cross‐couplings with established substrates, and facilitates the first Ni‐catalyzed C?N cross‐couplings of primary five‐ or six‐membered ring heteroarylamines and activated (hetero)aryl chlorides, with synthetically useful scope that is competitive with Pd catalysis.     

Base‐Mediated Transition‐Metal‐Free Dehydrative C−C and C−N Bond‐Forming Reactions from Alcohols

In recent years, there has been an increasing interest in using alcohols as alkylating agents for C?C and C?N bond‐forming processes employing mainly TM‐catalysts. Although BH‐catalysis looks like a green atom economy process since water is the only by‐product, it often suffers from one or more drawbacks, such as the use of expensive noble metal complexes, capricious ligands, and toxic organic solvents. Therefore, straightforward, efficient, atom economy and environmentally benign alternative protocols are desirable. This review aims to summarize the current knowledge within the published literature about dehydrative processes developed without TM‐catalysts. The most recent contributions to this topic have been reviewed keeping into account the new findings reported in this area. The features, strengths, and limitations of these alcohol‐based C?C and C?N bond‐forming processes has also been taken into account.     

Fused‐Ring Formation by an Intramolecular “Cut‐and‐Sew” Reaction between Cyclobutanones and Alkynes

The development of a catalytic intramolecular “cut‐and‐sew” transformation between cyclobutanones and alkynes to construct cyclohexenone‐fused rings is described herein. The challenge arises from the need for selective coupling at the more sterically hindered proximal position, and can be addressed by using an electron‐rich, but less bulky, phosphine ligand. The control experiment and ¹³C‐labelling study suggest that the reaction may start with cleavage of the less hindered distal C?C bond of cyclobutanones, followed by decarbonylation and CO reinsertion to enable Rh insertion at the more hindered proximal position.     

Rhodium(III)‐Catalyzed CC and CO Coupling of Quinoline N‐Oxides with Alkynes: Combination of CH Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C? H activation of arenes assisted by an oxidizing N? O or N? N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N? O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N? O bonds in both C? H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N? O bond acts as both a directing group for C? H activation and as an O‐atom donor.     

C[triple‐bond]C—H⋯N hydrogen bonding in 3‐methylthio‐4‐propargylthioquinoline

The title compound, C₁₃H₁₁NS₂, contains a C[triple‐bond]C—H?N hydrogen bond to a pyridine‐type N atom, with a C?N distance of 3.305 (4) Å and an H?N distance of 2.28 Å. This is one of the shortest C—H?N hydrogen bonds known.     

Differential Behavior of Amino–Imino Constitutional Isomers in Nonlinear Optical Processes

A detailed study of the “blocked” amino–imino tautomers derived from N‐acridine‐substituted 2‐aminobenzothiazole—and their effect on the nonlinear optical response—is presented. The synthesis, characterization, and nonlinear optical properties of these frozen tautomers, namely, N‐methyl‐N‐(2‐nitroacridin‐6‐yl)‐2‐aminobenzothia‐zole and 3‐methyl‐N‐(7‐nitroacridin‐3‐yl)‐2‐iminobenzothiazole, are reported. A theoretical model based on valence–bond theory is also proposed and used to analyze the effects of the nuclear configuration corresponding to each frozen tautomer structure. In the present case, the aromatic form and the allylic‐anion‐like system of the ? N? C? N? group inherent to each isomer are crucial for understanding and analyzing the different responses of each “blocked” tautomer.     

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy‐, epi‐, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2‐oxoglutarate‐dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, “natural” structure and thus transforms various non‐natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C?C bond formation by C?H activation or hydroxylation at the benzylic position prone to ring closure.