Ru-, Rh-, and Pd-Catalyzed C-C Bond Formation Involving C-H Activation and Addition on Unsaturated Substrates: Reactions and Mechanistic Aspects

The chemistry of copper is extremely rich because it can easily access Cu0, CuI, CuII, and CuIII oxidation states allowing it to act through one-electron or two-electron processes. As a result, both radical pathways and powerful two-electron bond forming pathways via organmetallic intermediates, similar to those of palladium, can occur. In addition, the different oxidation states of copper associate well with a large number of different functional groups via Lewis acid interactions or π-coordination. In total, these feature confer a remarkably broad range of activities allowing copper to catalyze the oxidation and oxidative union of many substrates.

Oxygen is a highly atom economical, environmentally benign, and abundant oxidant, which makes it ideal in many ways.1 The high activation energies in the reactions of oxygen require that catalysts be employed.2 In combination with molecular oxygen, the chemistry of copper catalysis increases exponentially since oxygen can act as either a sink for electrons (oxidase activity) and/or as a source of oxygen atoms that are incorporated into the product (oxygenase activity). The oxidation of copper with oxygen is a facile process allowing catalytic turnover in net oxidative processes and ready access to the higher CuIII oxidation state, which enables a range of powerful transformations including two-electron reductive elimination to CuI. Molecular oxygen is also not hampered by toxic byproducts, being either reduced to water, occasionally via H2O2 (oxidase activity) or incorporated into the target structure with high atom economy (oxygenase activity). Such oxidations using oxygen or air (21% oxygen) have been employed safely in numerous commodity chemical continuous and batch processes.3

However, batch reactors employing volatile hydrocarbon solvents require that oxygen concentrations be kept low in the head space (typically <5–11%) to avoid flammable mixtures, which can limit the oxygen concentration in the reaction mixture.4,5,6 A number of alternate approaches have been developed allowing oxidation chemistry to be used safely across a broader array of conditions. For example, use of carbon dioxide instead of nitrogen as a diluent leads to reduced flammability.5 Alternately, water can be added to moderate the flammability allowing even pure oxygen to be employed.6 New reactor designs also allow pure oxygen to be used instead of diluted oxygen by maintaining gas bubbles in the solvent, which greatly improves reaction rates and prevents the build up of higher concentrations of oxygen in the head space.4a,7 Supercritical carbon dioxide has been found to be advantageous as a solvent due its chemical inertness towards oxidizing agents and its complete miscibility with oxygen or air over a wide range of temperatures.8 An number of flow technologies9 including flow reactors,10 capillary flow reactors,11 microchannel/microstructure structure reactors,12 and membrane reactors13 limit the amount of or afford separation of hydrocarbon/oxygen vapor phase thereby reducing the potential for explosions.

Enzymatic oxidizing systems based upon copper that exploit the many advantages and unique aspects of copper as a catalyst and oxygen as an oxidant as described in the preceding paragraphs are well known. They represent a powerful set of catalysts able to direct beautiful redox chemistry in a highly site-selective and stereoselective manner on simple as well as highly functionalized molecules. This ability has inspired organic chemists to discover small molecule catalysts that can emulate such processes. In addition, copper has been recognized as a powerful catalyst in several industrial processes (e.g. phenol polymerization, Glaser-Hay alkyne coupling) stimulating the study of the fundamental reaction steps and the organometallic copper intermediates. These studies have inspiried the development of nonenzymatic copper catalysts. For these reasons, the study of copper catalysis using molecular oxygen has undergone explosive growth, from 30 citations per year in the 1980s to over 300 citations per year in the 2000s.

A number of elegant reviews on the subject of catalytic copper oxidation chemistry have appeared. Most recently, reviews provide selected coverage of copper catalysts14 or a discussion of their use in the aerobic functionalization of C–H bonds.15 Other recent reviews cover copper and other metal catalysts with a range of oxidants, including oxygen, but several reaction types are not covered.16 Several other works provide a valuable overview of earlier efforts in the field.17 This review comprehensively covers copper catalyzed oxidation chemistry using oxygen as the oxidant up through 2011. Stoichiometric reactions with copper are discussed, as necessary, to put the development of the catalytic processes in context. Mixed metal systems utilizing copper, such as palladium catalyzed Wacker processes, are not included here. Decomposition reactions involving copper/oxygen and model systems of copper enzymes are not discussed exhaustively. To facilitate analysis of the reactions under discussion, the current mechanistic hypothesis is provided for each reaction. As our understanding of the basic chemical steps involving copper improve, it is expected that many of these mechanisms will evolve accordingly.

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Aerobic Copper-Catalyzed Organic Reactions

Energetic salts offer many advantages over conventional energetic molecular compounds. The use of nitrogen containing anions and cations contributes to high heats of formations and high densities. Their low carbon and hydrogen content gives rise to a good oxygen balance. The decomposition of these compounds is predominantly through the generation of dinitrogen which makes them very promising candidates for highly energetic materials for industrial or military applications.

Energetic nitrogen-rich salts and ionic liquids.

s a hydrogen atom from the thiol to give hydroperoxide 96 and a thiyl radical, which propagates the chain. Hydroperoxide 96 is reduced in the presence of triphenyl phosphine to give the corresponding alcohol 91. The preference for the formation of cis-3,5-disubstituted 1,2-dioxolanes is in agreement with the Beckwith−Houk transition state model for 5-exo-trig cyclizations. Similarly, the addition of thiophenol onto 5methylhepta-1,3,6-triene 97 under an atmosphere of oxygen led to 1,2-dioxolane 98, isolated in 49% as a single diastereoisomer after treatment with triphenyl phosphine, together with minor amounts of linear alcohols 99 and 100 (Scheme 49, eq b). This reaction is remarkable for a number of reasons. First, the addition of the thiyl radical occurs exclusively at the terminal position of the conjugated diene system and not at the terminal alkene, thus highlighting the higher reactivity of conjugated dienes as compared to isolated alkenes. Second, intermolecular trapping of the resulting allyl radical is reversible and regioselective under these reaction conditions. Because of the reversibility of the reaction between the allyl radical and molecular oxygen, both ratios 1,4/1,2-addition and 1,2dioxolane/linear alcohols strongly depend upon the initial concentration in thiol. Accordingly, the 1,2-dioxolanes were obtained in good yields only in highly diluted solutions. Finally, the 5-exo-trig cyclization occurs in a completely stereoselective manner, with only one of the two diastereomeric peroxyl radical intermediates (101) undergoing cyclization, while the other one (102) either leads to linear alcohol 99 or fragments back the allyl radical (Scheme 49, eq b). The reversible reaction of allyl radicals with molecular oxygen was also demonstrated for carotenoid-derived carbon-centered radical generated by Scheme 47 Scheme 48. Application to the Preparation of Functionalized 1,2,4-Trioxanes Chemical Reviews Review dx.doi.org/10.1021/cr400441m | Chem. Rev. XXXX, XXX, XXX−XXX X addition of a thiyl radical to the conjugated polyene carotene. This process has been extended to include the more challenging 1,5-dienes, from which six-membered ring endoperoxides can be obtained. Bachi and co-workers applied the thiol−olefin cooxidation process to the total synthesis of antimalarial agent yingzhaosu A (Scheme 50) and its C14epimer, as well as the preparation of a series of active analogues, from readily available limonene 103. The overall process is extremely challenging in this case due to the particular structure of the diene, with the 6-exo-cyclization process being in competition with intermolecular hydrogen atom abstraction from the thiol, and also potentially with intramolecular hydrogen abstraction from the activated allylic position by the reactive oxygen-centered radical. As previously observed, addition of the thiyl radical takes place at the less hindered position, and due to the lack of stereocontrol during the trapping of the resulting carbon-centered radical, peroxyl radical 105 is formed as a 1:1 mixture of diastereoisomers (Scheme 50). The latter undergoes 6-exo-trig cyclization to give carbon-centered radical 106. Unlike the initial trapping with molecular oxygen, the 2,3-dioxabicyclo[3.3.1]nonane system of 106 allows a highly diastereoselective reaction for the second trapping with molecular oxygen from the less hindered face to give 107. Alcohol 104 is then obtained following hydrogen abstraction from the thiol by peroxyl radical 107 and reduction of the resulting hydroperoxide with triphenylphosphine. The yields of endoperoxides remain relatively low (ca. 20−30%, calculated on the diene); however, considering the accessibility and the cost of the reactants (thiophenol, limonene, and oxygen), this approach represents a very attractive access to these structurally complex endoperoxides, some of which exhibit very promising activity for the treatment of malaria. 3.3.2. Intramolecular Trapping of the Carbon-Centered Radical. 3.3.2.a. Fragmentation Reaction: RingOpening of Vinyl Cyclopropanes. The carbon-centered radicals generated by addition of a thiyl radical onto the C C bond of vinylcypropanes have been shown to undergo cyclopropane ring-opening. The resulting radical species can then be trapped by hydrogen abstraction from the thiol. This fragmentation is a very fast process with rate constants in the range 10−10 s−1 (310 K) for most of the cyclopropylcarbinyl radicals, which allows for the fragmentation process to compete favorably with intermolecular reactions, as well as with most intramolecular processes. Alternatively, the carboncentered radical resulting from the β-fragmentation of the cyclopropylmethyl radical can engage further in carbon−carbon bond-forming processes. The allylsulfide moiety allows for the addition of radicals with concomitant release of a thiyl radical, and very elegant processes using only substoichiometric amounts of a source of thiyl radicals have been developed for the rearrangement of vinylcyclopropanes (see section 5.2.1.e). In particular, under nonreducing conditions and in the presence of an external olefin, efficient annulation reactions have been achieved, giving access to polycyclic compounds. The carboncentered radicals generated by the thiol-mediated ring-opening Scheme 49 Scheme 50 Chemical Reviews Review dx.doi.org/10.1021/cr400441m | Chem. Rev. XXXX, XXX, XXX−XXX Y of vinylcyclopropanes could also be trapped to form a new carbon−heteroatom bond. Here again, annulations taking advantage of the allylsulfide moiety have been developed (see section 5.2.1.e). Landais, Renaud, and co-workers used vinyl cyclopentenes such as 108, easily prepared by monocyclopropanation of silylcyclopentadienes, as radical acceptors for photogenerated thiyl radicals. The reversible addition of the thiyl radical onto the CC bond of 108 leads eventually to cyclopropylcarbinyl radical 110, which undergoes fragmentation to give carboncentered radical 111, stabilized by the neighboring ester group. Hydrogen atom abstraction from the thiol then furnishes cyclopentene 109 and regenerates a thiyl radical that propagates the chain (Scheme 51, eq a). The addition of the thiyl radical at the β-carbon center takes place in a highly stereoselective manner, opposite to the bulky silyl group. The fate of the stabilized carbon-centered radical resulting from the fragmentation process depends upon the reaction conditions. For instance, Naito and co-workers reported the use of vinylcylopropyl oxime ethers such as 112 in domino reactions promoted by a thiol or a disulfide in the presence of triethylborane. The ring-opening of the cyclopropyl moiety is initiated by addition of a thiyl radical onto the terminal position of vinylcyclopropyl oxime ether 112. The stabilized carboncentered radical resulting from the fragmentation process reacts with triethylborane to form a boryl enamine 115 (Scheme 51, eq b). Depending on the reaction conditions, the latter can engage further in a radical oxygenation process, leading eventually to α-hydroxy oxime ether 113 after reduction of peroxyl radical 116 by the thiol (Scheme 51, eq b). Alternatively, 113 can react with aldehydes in an ionic aldol process to give β-hydroxy oxime ethers in a stereoselective manner, as illustrated by the preparation of 117 from 112 (Scheme 51, eq c). In the aforementioned reactions, the allylsulfide moieties generated upon addition of a thiyl radical onto the vinylcyclopropane unit remain intact at the end of the reaction. However, radical reactions taking advantage of the fragmentation of allyl sulfides upon addition of radical species are also well documented. Some examples of intermolecular additions, as well as cyclization and annulation processes, will be described in section 5.2.1.e. 3.3.2.b. Rearrangement and Cyclization of Nonconjugated Dienes. In the addition of thiyl radicals onto nonconjugated dienes, the CC bonds can either react independently or lead to rearrangements through intramolecular trapping of the carbon-centered radical generated in the initial addition step. In many cyclic dienes, addition occurs selectively at the more strained double bond, and products resulting from rearrangements are often observed. For example, the addition of thiophenol to 5-methylene-norbornene led to the exo addition products 118 and 119, together with tricyclic adduct 120. The latter results from the rearrangement of homoallyl radical intermediate 121 into cyclopropylcarbinyl radical 122 (Scheme 52). Similar rearrangements have been observed in norbornadiene derivatives where substitution at C-7 can influence facial selectivity, while substitution of the methylene bridge in 7,7-dimethylnorbornene proved to have no effect in directing the addition of thiophenol. The formation of cyclopropylcarbinyl radical intermediates in norbornadiene derivatives can also lead to other skeletal rearrangements, as illustrated by the addition of thiophenol to hexachloronorbornadiene 123, which results in the formation of 125, beside the expected 1:1 addition product 124 (Scheme 53, eq a). Following addition of the thiyl radical, presumably from the less hindered endo-face, and subsequent 3-exo-trig cyclization onto the neighboring CC bond, cyclopropylcarbinyl radical 126 undergoes fragmentation to give the more stable α-chlorosubScheme 51 Scheme 52 Chemical Reviews Review dx.doi.org/10.1021/cr400441m | Chem. Rev. XXXX, XXX, XXX−XXX Z stituted carbon-centered radical 127. The latter then abstracts a hydrogen atom from the thiol to give 125 (relative configuration not established) and a thiyl radical, which goes on to propagate the chain. Similar rearrangement was observed i n t h e add i t i on o f t BuSH on to 1 , 2 , 3 , 4 , 7 , 7 hexamethylbicyclo[2.2.1]heptadiene. Likewise, Hodgson and co-workers have observed complete skeletal rearrangements in the addition of thiophenol to 7-azabicyclo[2.2.1]heptadienes such as 128 (Scheme 53, eq b). Transa

Thiyl Radicals in Organic Synthesis

The [2 + 2] photocycloaddition is undisputedly the most important and most frequently used photochemical reaction. In this review, it is attempted to cover all recent aspects of [2 + 2] photocycloaddition chemistry with an emphasis on synthetically relevant, regio-, and stereoselective reactions. The review aims to comprehensively discuss relevant work, which was done in the field in the last 20 years (i.e., from 1995 to 2015). Organization of the data follows a subdivision according to mechanism and substrate classes. Cu(I) and PET (photoinduced electron transfer) catalysis are treated separately in sections 2 and 4, whereas the vast majority of photocycloaddition reactions which occur by direct excitation or sensitization are divided within section 3 into individual subsections according to the photochemically excited olefin.

http://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.5b00723

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2+2] Photocycloaddition Reactions

Dimerization of 1-alkynes catalyzed by RhCl(PMe3)3. Isolation of the intermediate (alkynyl)(vinyl)rhodium(III) complexes

Novel Convenient Method for the Synthesis of N,N-Bis(trimethylsilyloxy)enamines

New styryl dyes of the pyridine and benzothiazole series were synthesized with the aim of investigating the solid-state [2+2] autophotocycloaddition (PCA) reaction. The 1H NMR spectroscopy showed that for most of the compounds under study, the visible light irradiation of thin polycrystalline films of the dyes affords cyclobutane derivatives. The rate of the photoreaction depends on the structure of the dye and is higher for compounds, which contain a short N-substituent in the heterocyclic moiety and have strong absorption in the visible region. Dyes bearing electron-releasing substituents in the benzene ring undergo the stereospecific PCA in the syn-head-to-tail dimeric pair to give the only rctt isomer of cyclobutane derivatives. Electron-withdrawing and bulky substituents in the benzene fragment of styryl dyes extend the range of the mutual orientations of the molecules in the dimeric pairs, resulting in the formation of two or even four isomeric cyclobutanes in the PCA reactions. The structures of some dyes were established by X-ray diffraction. In the overwhelming majority of the structures, one of two packing modes, either syn-head-to-tail or syn-head-to-head, with extensive stacking interactions is observed. A rare example of the anti-head-to-head stacking mode was found for the dicationic dye containing the bulky N+(Et)Me2 substituent in the benzene ring. The syn-head-to-tail and anti-head-to-head stacking modes can facilitate the PCA reaction due to the close spatial proximity of the ethylenic bonds and their parallel orientation in the dimeric pairs of the dye molecules.

Styryl dyes. Synthesis and study of the solid-state [2+2] autophotocycloaddition by NMR spectroscopy and X-ray diffraction

On the structure and spectra of dinitramide salts

A new approach to the synthesis of benzo[e][1,2,3,4]tetrazine 1,3-dioxides involves the treatment ofN-nitroanilines containing anortho-(tert-butyl-NNO-azoxy) group with phosphoric anhydride or phosphorus pentachloride. The reaction is supposed to proceed through an intermediate diazonium oxide cation.

Yu. A. Strelenko

Papers

Dimerization of 1-alkynes catalyzed by RhCl(PMe3)3. Isolation of the intermediate (alkynyl)(vinyl)rhodium(III) complexes

Novel Convenient Method for the Synthesis of N,N-Bis(trimethylsilyloxy)enamines

Styryl dyes. Synthesis and study of the solid-state [2+2] autophotocycloaddition by NMR spectroscopy and X-ray diffraction

On the structure and spectra of dinitramide salts

New approach to the synthesis of benzo[e][1,2,3,4]tetrazine 1,3-dioxides