Intramolecular C-H oxidation

Intramolecular C-H oxidative additions have been common for many years. These reactions are known as cyclometallations (or orthometallations when the metal undergoes addition of an ortho C-H bond of the aromatic group of a ligand). Examples are provided in Equations 6.22-6.25. " Cyclometallations of azobenzene are common and constitute some of the earliest examples of C-H activation. Two examples with Co2(CO)j and Cp Ni are shown in Equation 6.22 the product from the reac-... 

The presence of a hydride cis to the ri -arene allowed spectroscopic analysis to be carried out on the complex. At variable temperature the complex was observed to exhibit C-H oxidative addition into the benzene proton in an intramolecular fashion. The NMR spectral analysis at variable temperature were performed to calculate the energy barrier needed for such a reaction to occur which supported an intramolecular C-H oxidative addition step. The energy barrier (AG ) to arene C H oxidative addition for the benzene hydride adduct was found to be 12.7 kcal/mol. Kinetic isotope studies were also done on other substituted benzene analogues as well as the benzene phenyl adduct, all pointing towards the same outcome. Here the ktijkYy value for the benzene phenyl adduct was found to be 3.0 at 259 K, which is consistent with significant C-H(D) bond cleavage to reach the transition state. 

Scheme 15.53 Copper-catalysed intramolecular C-H oxidation/acylation with formyl-W-arylformamides.

It was first theorized by Kaska in 1983 [19] that the formation of PCP double cyclometallated complexes of the type (77) could arise from the intramolecular C— H oxidative addition of a tert-butyl C—H of the PCP ligand (Scheme 2.36). Although the authors claimed the observation of this sort of species, the evidence shown was not conclusive [19]. 

A novel CuClj-catalyzed intramolecular C-H oxidation/acylation protocol using two C—H bonds as the reaction partners and Oj as the terminal oxidant was reported by Li and coworkers (Scheme 8.36). Various substituted indoline-2,3-diones could be prepared in moderate to good yields with high tolerance of functional groups. The kinetic isotope effect = 2 4) was observed by FTIR... 

Chapter Synthesis of 12- to 16-Membered-Ring Lactones is dedicated to the synthesis of 12- to 16-membered ring lactones. In this chapter, M. Kalesse and M. Cordes present an overview of the macrocyclization of seco-acids as well as new effective procedures to access 12- to 16-membered ring lactones such as ringclosing metatheses of alkynes and olefins. The authors also report the use of ketene sources and benzodioxinones to produce macrocyclic lactones. Nitrile oxide-olefin cycloaddition, intramolecular C-H oxidative macrolactonization, and Yamaguchi and Mukaiyama macrocyclization as well as macrolactonization via thioester or using phosphorus reagents are described. 

Using the results of an earlier study concerning enantioselective copper-catalyzed intramolecular C—H insertion of metal carbenoids,109 an interesting system for optimizing the proper combination of ligand, transition metal, and solvent for the reaction of the diazo compound (75) was devised (see Scheme 19).110 The reaction parameters were varied systematically on a standard 96-well microtiter/filtration plate. A total of five different ligands, seven metal precursors, and four solvents were tested in an iterative optimization mode. Standard HPLC was used to monitor stereoselectivity following DDQ-induced oxidation. This type of catalyst search led to the... 

Perhaps, many of the intramolecular C-H activations that are known for metal ligand complexes are actually best described as electrophilic substitutions rather than oxidative additions. A very large number of palladium(II) complexes are known to react intramolecularly to the metallated species. 

Like carbene insertions into carbon-hydrogen bonds, metal nitrene insertions occur in both intermolecular and intramolecular reactions.For intermole-cular reactions, a manganese(III) meio-tetrakis(pentafluorophenyl)porphyrm complex gives high product yields and turnovers up to 2600 amidations could be effected directly with amides using PhI(OAc)2 (Eq. 51). The most exciting development in intramolecular C—H reactions thus far has been the oxidative cychzation of sulfamate esters (e.g., Eq. 52), as well as carbamates (to oxazolidin-2-ones), ° and one can expect further developments that are of synthetic... 

The intramolecular C-H insertion reaction of phenyldiazoacetates on cyclohexadiene, utilizing the catalyst Rh2(S-DOSP)4, leads to the asymmetric synthesis of diarylacetates (Scheme 8). Utilizing the phenyl di azoacetate 38 and cyclohexadiene, the C-H insertion product 39 was produced in 59% yield and 99% ee. Oxidative aromatization of 39 with DDQ followed by catalytic hydrogenation gave the diarylester 40 in 96% ee. Ester hydrolysis followed by intramolecular Friedel-Crafts gave the tetralone 31 (96% ee) and represents a formal synthesis of sertraline (5). Later studies utilized the catalyst on a pyridine functionalized highly cross-linked polystyrene resin. ... 

A plausible mechanism for the one-pot synthesis ofcarbazoles is shown in Scheme 5. It consists of two interlinked catalytic cycles. In the first cycle a classical Buchwald-Hartwig amination reaction occurs to generate an intermediate 5 which then enters the second cycle by oxidative addition to Pd(0). The resulting Pd(II) complex then undergoes intramolecular C-H activation to give a six-membered palladacycle which subsequently yields the carbazole by reductive elimination. 

Also developed by Hill is a photochemical system (equations 41 to 48) based on a polyoxoacid, H3PW12O40 (P)- The excited state of the acid probably oxidizes the alkane in the first step. The radical can then either attack the solvent to give an iminium radical, which leads to ketone on hydrolysis, or it can be oxidized to the carbonium ion, in which case attack on the solvent leads instead to the iV-alkyl-acetamide. If the substrate has two adjacent tertiary C—bonds, then alkenes tend to be formed, llie Barton reaction, normally known as an intramolecular C—H activation, can give some intermolecular reaction in some examples. Thus, when n-octyl nitrite is photolyzed in heptane, some nitrosoheptane is observed. ... 

Orthometallation of triarylphosphine and triarylphosphite at mthenium has long been knovm as intramolecular C-H bond activation in ruthenium chemistry [2], but did not receive attention from organic chemists. In 1965, Chatt and Davidson documented that a Ru(0) complex, which was formed by two-electron reduction of Ru(II) by use of sodium naphthalene is capable of reversible cleavage of sp C-H bonds of naphthalene by oxidative addition/reductive elimination processes (Scheme 14.1) [3]. 

A much wider range of organopalladium compounds is available, however, by means of cyclopalladation reactions. Such reactions involve a Pd(II) salt and an N or P ligand capable of undergoing intramolecular C—H bond oxidative addition. HCl is eliminated as a by-product, and the reactions occur most readily when a five-membered chelate ring is formed " ... 

Finally, electrophilic addition of H(C6F5)3, a strong Lewis acid, to a Cp ligand yields an T 4—Cp Re complex 38. Oxidative addition of a C-H bond (intramolecular C-H bond activation) from the r 4-Cp ring results in a zwitterionic rhenium dihydride, as shown in equation 8.72.101... 

---