Palladium‐Catalyzed Cyanation of Carbon?Carbon Triple Bonds Under Aerobic Conditions

Essential oxygen : The title transformation involves two different modes of cyanation, syn and anti cyanopalladation, as the key steps in this catalytic reaction. These processes enable successful dicyanative cyclization of diyne and enyne derivatives (see scheme).

     

Rhodium(I)‐Catalyzed Enantioselective C?C Bond Activation

Relieving the strain : The rhodium(I)‐catalyzed activation of C C bonds in functionalized cyclobutanes opens a novel route to highly substituted carbo‐ and heterocycles. Particularly intriguing is the differentiation of enantiotopic C C bonds, which leads to the formation of highly enantiomerically enriched lactones, cyclopentanones, and cyclohexenones (see scheme).

     

Rhodium(I)‐Catalyzed Cycloisomerization of Benzylallene‐Alkynes through C?H Activation

The efficient Rh^I‐catalyzed cycloisomerization of benzylallene‐alkynes produced the tricyclo[9.4.0.0^3,8]pentadecapentaene skeleton through a C H bond activation in good yields. A plausible reaction mechanism proceeds via oxidative addition of the acetylenic C H bond to Rh^I, an ene‐type cyclization to the vinylidenecarbene–Rh^I intermediate, and an electrophilic aromatic substitution with the vinylidenecarbene species. It was proposed based on deuteration and competition experiments.     

Iron‐Catalyzed Chemoselective ortho Arylation of Aryl Imines by Directed C?H Bond Activation

Naheliegende Alternative : Eine eisenkatalysierte Imin‐gesteuerte C‐H‐Aktivierung mit einem Diarylzinkreagens führt eine Arylgruppe in ortho‐Stellung an einem von Acetophenon abgeleiteten Imin ein (siehe Schema); mit einem Palladiumkatalysator tritt dagegen eine gewöhnliche Substitution auf. Die Titelreaktion ist eine milde C‐H‐Aktivierung, die in Gegenwart von 1,2‐Dichlorisobutan mit Arylbromiden, ‐chloriden oder ‐sulfonaten selektiv verläuft.

     

Iron‐Catalyzed Chemoselective ortho Arylation of Aryl Imines by Directed C?H Bond Activation

No Fe‐ar : Iron catalyzes an imine‐directed C? H bond activation to introduce an ortho‐aryl group to an acetophenone‐derived imine using a diarylzinc reagent (see scheme), whereas palladium catalyzes the conventional substitution reaction . The title reaction features mild and selective C? H bond activation in the presence of aryl bromide, chloride, or sulfonate groups, and 1,2‐dichloroisobutane is essential to achieve such selectivity.

     

Highly Enantioselective Rhodium(I)‐Catalyzed Carbonyl Carboacylations Initiated by C?C Bond Activation

The lactone motif is ubiquitous in natural products and pharmaceuticals. The Tishchenko disproportionation of two aldehydes, a carbonyl hydroacylation, is an efficient and atom‐economic access to lactones. However, these reaction types are limited to the transfer of a hydride to the accepting carbonyl group. The transfer of alkyl groups enabling the formation of C C bonds during the ester formation would be of significant interest. Reported herein is such asymmetric carbonyl carboacylation of aldehydes and ketones, thus affording complex bicyclic lactones in excellent enantioselectivities. The rhodium(I)‐catalyzed transformation is induced by an enantiotopic C C bond activation of a cyclobutanone and the formed rhodacyclic intermediate reacts with aldehyde or ketone groups to give highly functionalized lactones.     

Palladium‐Catalyzed Dearomative Cyclocarbonylation by C?N Bond Activation

A fundamentally novel approach to bioactive quinolizinones is based on the palladium‐catalyzed intramolecular cyclocarbonylation of allylamines. [Pd(Xantphos)I₂], which features a very large bite angle, has been found to facilitate the rapid carbonylation of azaarene‐substituted allylamines into bioactive quinolizinones in good to excellent yields. This transformation represents the first dearomative carbonylation and is proposed to proceed by palladium‐catalyzed C N bond activation, dearomatization, CO insertion, and a Heck reaction.     

Isomerization of Olefins Triggered by Rhodium‐Catalyzed C?H Bond Activation: Control of Endocyclic β‐Hydrogen Elimination

Five‐membered metallacycles are typically reluctant to undergo endocyclic β‐hydrogen elimination. The rhodium‐catalyzed isomerization of 4‐pentenals into 3‐pentenals occurs through this elementary step and cleavage of two C H bonds, as supported by deuterium‐labeling studies. The reaction proceeds without decarbonylation, leads to trans olefins exclusively, and tolerates other olefins normally prone to isomerization. Endocyclic β‐hydrogen elimination can also be controlled in an enantiodivergent reaction on a racemic mixture.     

Diastereoselective Carbocyclization of 1,6‐Heptadienes Triggered by Rhodium‐Catalyzed Activation of an Olefinic C?H Bond

The use of α,ω‐dienes as functionalization reagents for olefinic carbon–hydrogen bonds has been rarely studied. Reported herein is the rhodium(I)‐catalyzed rearrangement of prochiral 1,6‐heptadienes into [2,2,1]‐cycloheptane derivatives with concomitant creation of at least three stereogenic centers and complete diastereocontrol. Deuterium‐labeling studies and the isolation of a key intermediate are consistent with a group‐directed C H bond activation, followed by two consecutive migratory insertions, with only the latter step being diastereoselective.     

Platinum(II)‐Catalyzed Intramolecular Cyclization of o‐Substituted Aryl Alkynes through sp3 C?H Activation

Ring leader : PtCl₂ catalyzes intramolecular cyclization of o‐isopropyl or o‐benzyl aryl alkynes to give substituted indene derivatives with good yields and high selectivity. This reaction appears to proceed through an sp³ C? H activation and 1,4‐hydrogen migration pathway (see scheme).

     

Highly Enantioselective Rhodium(I)‐Catalyzed Activation of Enantiotopic Cyclobutanone C?C Bonds

The selective functionalization of carbon–carbon σ bonds is a synthetic strategy that offers uncommon retrosynthetic disconnections. Despite progress in C C activation and its great importance, the development of asymmetric reactions lags behind. Rhodium(I)‐catalyzed selective oxidative additions into enantiotopic C C bonds in cyclobutanones are reported. Even operating at a reaction temperature of 130 °C, the process is characterized by outstanding enantioselectivity with the e.r. generally greater than 99.5:0.5. The intermediate rhodacycle is shown to react with a wide variety of tethered olefins to deliver complex bicyclic ketones in high yields.     

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.     

Metal‐Catalyzed α‐Arylation of Carbonyl and Related Molecules: Novel Trends in C?C Bond Formation by C?H Bond Functionalization

α‐Arylated carbonyl compounds are commonly occurring motifs in biologically interesting molecules and are therefore of high interest to the pharmaceutical industry. Conventional procedures for their synthesis often result in complications in scale‐up, such as the use of stoichiometric amounts of toxic reagents and harsh reaction conditions. Over the last decade, significant efforts have been directed towards the development of metal‐catalyzed α‐arylations of carbonyl compounds as an alternative synthetic approach that operates under milder conditions. This Review summarizes the developments in this area to date, with a focus on how the substrate scope has been expanded through selection of the most appropriate synthetic method, such as the careful choice of ligands, precatalysts, bases, and reaction conditions.