Stefano Protti

Carbon–Carbon Bond Forming Reactions via Photogenerated Intermediates

The present review offers an overview of the current approaches for the photochemical and photocatalytic generation of reactive intermediates and their application in the formation of carbon-carbon bonds. Valuable synthetic targets are accessible, including arylation processes, formation of both carbo- and heterocycles, alpha- and beta-functionalization of carbonyls, and addition reactions onto double and triple bonds. According to the recent advancements in the field of visible/solar light catalysis, a significant part of the literature reported herein involves radical ions and radicals as key intermediates, with particular attention to the most recent examples. Synthetic application of carbenes, biradicals/radical pairs and carbocations have been also reported.

Photocatalytic CH Activation by Hydrogen‐Atom Transfer in Synthesis

This minireview encompasses the most recent (since 2010) advancements in the field of photocatalytic hydrogen‐atom transfer (HAT) processes for CH bond functionalization. The direct HAT process promoted from the excited state of a photocatalyst is limited to the classes of polyoxometalates and aromatic ketones, but alternative photocatalytic strategies have recently been devised to alleviate this shortcoming, making use of indirect HAT reactions. The applications of these two approaches in organic synthesis, including the formation of CC, as well as Chalogen, CO (CO), and CN bonds, are presented herein.

Photochemistry in synthesis: Where, when, and why

A series of photochemical reactions are assessed under the environmental aspect by using Eissen and Metzgers EATOS (environmental assessment tool for organic syntheses) method and are compared with strictly analogous thermal processes. These include C-C bond-forming reactions (arylation and alkylation) and selective oxidation and reduction reactions. In most cases, the photochemical method is experimentally simpler and less expensive than the thermal alternative. A disadvantage is that photochemical reactions are carried out in rather dilute solution, and this factor gives by far the main contribution to the assessment. However, if the solvent is recovered, the photochemical reaction is more environment-friendly.

Photoinduced Multicomponent Reactions

The combination of multicomponent approaches with light-driven processes opens up new scenarios in the area of synthetic organic chemistry, where the need for sustainable, atom- and energy-efficient reactions is increasingly urgent. Photoinduced multicomponent reactions are still in their infancy, but significant developments in this area are expected in the near future.

Photochemical technologies assessed: the case of rose oxide

The environmental burdens of the synthesis of rose oxide have been evaluated by means of green metrics (EATOS, LCA) applied to six thermal and photochemical processes. The contributions of supplied energy, employed chemicals (including solvents and additives) and waste disposal have been investigated. The results pointed out that the methods used for the assessment suffered from important limitations. At any rate, the photochemical alternative for this synthesis clearly has the advantage.

A photochemical route to 2-substituted benzo[b]furans.

2-Substituted benzo[b]furans were synthesized by a one-step metal-free photochemical reaction between 2-chlorophenol derivatives and terminal alkynes by tandem formation of an aryl-C and a C-O bond via an aryl cation intermediate. The mild conditions and the application to chlorophenols rather of the more expensive bromo or iodo analogues makes this procedure environmentally convenient.

Synthesis of γ-lactols, γ-lactones and 1,4-monoprotected succinaldehydes under moderately concentrated sunlight

The usefulness of solar light for carrying out photocatalytic reactions involving the formation of a carbon–carbon bond has been explored. Thus, some radical alkylations of α,β-unsaturated acids or aldehydes have been carried out in a mixed aqueous solution. Under these conditions, alkyl radicals are generated from i-PrOH and 1,3-dioxolane by photocatalyzed hydrogen abstraction. A water soluble photocatalyst (disodium benzophenondisulfonate, BPSS) was used, which greatly simplifies work up. With reasonably efficient radical traps (e.g. maleic acid), the syntheses could be carried out up to completion on a 10 gram scale within 10–15 hours exposure to sunlight in a solar concentrator (SOLFIN apparatus) in November in Almeria (Spain). The alkylation of some α,β-unsaturated aldehydes have been likewise performed under the same conditions.

Photoinduced three-component reaction: a convenient access to 3-arylacetals or 3-arylketals.

A mild and versatile method for the photoinduced three-component synthesis of 3-arylacetals and ketals is presented. Desired targets are smoothly obtained by irradiating aromatic halides or esters in alcohols, in the presence of vinyl ethers.

Light-Driven Activation of the [H2O(terpy)MnIII-μ-(O2)-MnIV(terpy)OH2] Unit in a Chromophore–Catalyst Complex

Fuel production using solar power is one of the most important challenges facing the scientific community this century. Nature stores the energy from light in the form of chemical bonds by a process called photosynthesis. In the early stages of this process, Photosystem II uses light to remove electrons and protons from water. In later steps, the electrons taken from water are used to make stable reduced products. This process has inspired the field of “artificial photosynthesis”, the aim of which is to duplicate the processes of light capture, the formation of charge separated states, charge accumulation, and the catalytic formation of high-energy products using molecular devices. One potential strategy involves the design of molecules that contain photoactive and catalytic units that promote photo-chemical oxidation reactions through the accumulation of sufficient light-driven oxidizing equivalents at a catalytic center. Our research group recently developed a ligand designed to hold both a photoactive unit and a putative catalytic center through an imidazole-based electron-relay moiety, which was shown to behave as a redox-active module. In this work, our aim is to expand this chromophore-relay complex in order to create a chromophore-relay-catalyst complex made up of a [Ru ACHTUNGTRENNUNG(bpy)2](L) complex covalently bound to a terpyridine unit through an imidazole bridge. Recently, terpyridine ligands have been increasingly used for manganeseand ruthenium-based catalytic systems with the aim of oxidizing water and organic substrates. Amongst recent publications in this area, one of the more interesting pieces of work concerns the dinuclear manganese complex [(Terpy)2(Mn -di-m-oxo-Mn)], which is one of the few manganese complexes to have been reported to perform the catalytic oxidation of water. Given the presence of the two coordinating sites in our target ligand (1,10-phenanthroline and a 2,2’:6’,2’’-terpyridine), a synthetic pathway had to be designed in order to obtain specific insertion of the manganese and ruthenium metals into each of the two sites. Preparation of the organic ligand prior to metal insertion did not provide this selectivity; therefore, this approach was discarded. Thus, we used a synthetic procedure based on a modified ruthenium–polypyridine complex known to be a useful building block from which our target molecule can be constructed. This approach yields a versatile synthon (1) that could be useful for the preparation of libraries of compounds through simple synthetic transformations; it relies on the inert nature of low-spin ruthenium(II)-polypyridine complexes, which prevent demetalation or ligand-exchange reactions under the conditions used. The ruthenium(II) heteroleptic complex containing two bipyridine ligands and a coordinated 1,10phenanthroline-4,5-dione (phendione) ligand [RuACHTUNGTRENNUNG(bpy)2(Phendione)]2+(1) was prepared in good yields using published methods. This complex was then reacted with 4’-benzaldehyde terpyridine in refluxing acetic acid in pres[a] Dr. C. Herrero, Dr. A. Quaranta, Dr. W. Leibl , Prof. A. W. Rutherford, Prof. A. Aukauloo CEA, iBiTecS, Service de Bio nerg tique Biologie Structurale et M canismes (SB2SM) Gif-sur-Yvette, F-91191 (France) Fax: + (33) 1 69088717 E-mail : christian.herrero@cea.fr [b] Dr. S. Protti Department of Chemistry University of Pavia V.Le Taramelli 12 27100 Pavia (Italy) [c] Prof. A. W. Rutherford Molecular Biosciences Imperial College South Kensington Campus, London SW7 2AZ (UK) [d] D. R. Fallahpour Institute of Organic Chemistry University of Zurich Winterthurerstrasse 190, CH8057, Zurich (Switzerland) [e] Dr. M.-F. Charlot, Prof. A. Aukauloo Laboratoire de Chimie Inorganique Institut de Chimie Mol culaire et des Mat riaux d’Orsay UMR 8182 Universit de Paris-Sud Orsay, F-91405 (France) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201100030.

Singlet/triplet phenyl cations and benzyne from the photodehalogenation of some silylated and stannylated phenyl halides

The photodehalogenation of fluoro or chlorobenzene derivatives smoothly generates triplet and singlet phenyl cations (3,1Ar+) and potentially benzyne. These intermediates lead to different products, which warrants exploring the direct effect of substituents. SiMe3 and SnMe3 groups have been found to be convenient probes since they affect neither the photophysics nor the primary dehalogenation of 4-chloroanisole and 4-chloro (or 4-fluoro) N,N-dimethylaniline (except for the case of 4-fluoro-3-(trimethylstannyl)aniline, which was preferentially demetallated). The stabilization by these groups (with SnMe3ca. 10 kcal mol−1 for the triplets and 20 kcal mol−1 for the singlets, as computed by using (U)B3LYP DFT method with LANL2DZ basis set) made 1Ar+ the lowest state with stannylated and silylated anisoles and solvolysis the main process. On the other hand, donating substituents and an acidic solvent favored the triplet cation chemistry, a quite general process leading to reduction or (in the presence of π bond nucleophiles) to arylation. Noteworthily, the stannylated 4-N,N-dimethylaminophenyl cation eliminated the Me3Sn+ group, opening an unprecedented path to the corresponding benzyne. Apart from the control of the chemical output, the photostabilizing effect found with a silyl group may be useful for designing less phototoxic fluorinated drugs.