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The first rhodium-catalyzed formylation of non-activated alkyl chlorides with syn gas (H 2 /CO) allows to produce aldehydes in high yields (25 examples). A catalyst optimization study revealed Rh(acac)(CO) 2 in the presence of 1,3-bisdiphenylphosphinopropane (DPPP) as the most active catalyst system for this transformation. Key for the success of the reaction is the addition of sodium iodide (NaI) to the reaction system, which leads to the formation of activated alkyl iodides as intermediates. Depending on the reaction conditions, either the linear or branched aldehydes can be preferentially obtained, which is explained by a different mechanism., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

A phosphine-oxide-promoted, cobalt-catalysed reductive etherification using syngas as a reductant is reported. This novel methodology was successfully used to prepare a broad range of unsymmetrical ethers from various aldehydes and alcohols containing diverse functional groups, and was scaled-up to multigram scale under comparably mild conditions. Mechanistic experiments support an acetalization-hydrogenation sequence., (© 2022 Wiley-VCH GmbH.)

Invited for the cover of this issue are Helfried Neumann, Matthias Beller and co-workers at the Leibniz-Institut für Katalyse e. V., Rostock and Hangzhou Normal University. The image depicts "the case of ketone deuteration" being solved by Sherlock Holmes. Read the full text of the article at 10.1002/chem.202100468., (© 2021 Wiley-VCH GmbH.)

A novel ruthenium-catalyzed C-H activation methodology for hydrogen isotope exchange of aromatic carbonyl compounds is presented. In the presence of catalytic amounts of specific amine additives, a transient directing group is formed in situ, which directs selective deuteration. A high degree of deuteration is achieved for α-carbonyl and aromatic ortho-positions. In addition, appropriate choice of conditions allows for exclusive labeling of the α-carbonyl position while a procedure for the preparation of merely ortho-deuterated compounds is also reported. This methodology proceeds with good functional group tolerance and can be also applied for deuteration of pharmaceutical drugs. Mechanistic studies reveal a kinetic isotope effect of 2.2, showing that the C-H activation is likely the rate-determining step of the catalytic cycle. Using deuterium oxide as a cheap and convenient source of deuterium, the methodology presents a cost-efficient alternative to state-of-the-art iridium-catalyzed procedures., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Introducing (per)fluoroalkyl groups into arenes continues to be an interesting, but challenging area in organofluorine chemistry. We herein report an ortho-selective C-H perfluoroalkylation including trifluoromethylations of anilines and indoles without the need of protecting groups using R f I and R f Br as commercially available reagents. The availability and price of the starting materials and the inherent selectivity make this novel methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks, for example, for bioactive compounds and materials., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Ruthenium PNP pincer complexes bearing supplementary cyclometalated C,N-bound ligands have been prepared and fully characterized for the first time. By replacing CO and H - as ancillary ligands in such complexes, additional electronic and steric modifications of this topical class of catalysts are possible. The advantages of the new catalysts are demonstrated in the general α-alkylation of ketones with alcohols following a hydrogen autotransfer protocol. Herein, various aliphatic and benzylic alcohols were applied as green alkylating agents for ketones bearing aromatic, heteroaromatic or aliphatic substituents as well as cyclic ones. Mechanistic investigations revealed that during catalysis, Ru carboxylate complexes are predominantly formed whereas neither the PNP nor the CN ligand are released from the catalyst in significant amounts., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

For the first time, the bidentate phosphinite ligand 1,2-bis(di-tert-butylphosphinoxy)ethane (tBu 2 POCH 2 CH 2 OPtBu 2 ) was synthesized. In the presence of this ligand, various N-acyl enamides were obtained in good yields and chemoselectivity by Pd-catalyzed carbonylation reaction of imines containing α-H. Meanwhile, imines without α-H could be transformed to N-acyl imines, which form highly hindered amides by straightforward addition of Grignard reagents., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Tetraadamantylbiphosphine (TABP; L1), which showed superior activity in the palladium-catalyzed cyanation of 4-chloroanisole compared to standard phosphines, was synthesized as a new ligand. The generality of the new catalytic system was shown by the cyanation reaction of approximately 30 (hetero)aryl halides including hindered, electron-rich, and electron-poor aryl chlorides. These reactions constitute the first examples of using biphosphine ligands in Pd-catalyzed coupling reactions., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A benign and efficient palladium-catalyzed aminocarbonylation reaction of allylic alcohols is presented. The generality of this novel process is demonstrated by the synthesis of β,γ-unsaturated amides including aliphatic, cinnamyl, and terpene derivatives. The choice of ligand is crucial for optimal carbonylation processes: Whereas in most cases the combination of PdCl2 with Xantphos (L6) gave best results, sterically hindered substrates performed better in the presence of simple triphenylphosphine (L10), and primary anilines gave the best results using cataCXium® PCy (L8). The reactivity of the respective catalyst system is significantly enhanced by addition of small amounts of water. Mechanistic studies and control experiments revealed a tandem allylic alcohol amination/C-N bond carbonylation reaction sequence., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A systematic study on the carbonylative transformation of 1-bromo-2-fluorobenzenes with various nucleophiles has been performed. Different types of double nucleophiles, such as NN, NC, OC, and NS, can be effectively applied as coupling partners. The corresponding six-membered heterocycles were isolated in moderate to good yields., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We describe here a novel procedure for the synthesis of highly substituted 2-quinolinones. By this newly developed approach, 2-quinolinone derivatives were prepared in moderate to good yields by carbonylative cyclization of N-aryl-pyridine-2-amines and internal alkynes by CH activation. Remarkably, [Mo(CO)6 ] was applied as a solid CO source and the reaction proceeded in an atom economic manner., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A concise and highly versatile method for the synthesis of functionalized isoindolinones is reported. Various 2-bromoanilines undergo palladium-catalyzed carbonylation with 2-formylbenzoic acid under a convenient and mild procedure to give good to excellent yields of the corresponding isoindolinones. Additionally, 2-halobenzaldehydes can be applied as substrates in palladium-catalyzed double-carbonylation to provide identical compounds in moderate to good yields., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A carbonylative α-arylation process employing unactivated nitriles for the first time is described. The reaction tolerates a range of (hetero)aryl iodides and several nitrile coupling partners. No prefunctionalization of the nitriles is necessary and the resulting β-ketonitriles are obtained in good to excellent yields. The methodology also allows for a convenient (13) C-labelling of the generated carbonyl moiety., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Combining commercially available bromoanilines and bromobenzonitriles in a novel double carbonylation process allows for a straightforward synthesis of isoindolo[1,2-b]quinazoline-10,12-diones. At least five different CC and/or CN bonds are selectively formed in this 3-component reaction, which likely proceeds through sequential carbonylation-cyclization-isomerisation-carbonylation steps. Notably, two molecules of CO are inserted in this highly efficient palladium-catalyzed process., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A ruthenium-catalyzed carbonylative CH bond arylation process for the three-component synthesis of complex aryl-(hetero)aryl ketones in an aqueous solution has been developed. By exploiting the ortho-activating effect of nitrogen-containing directing groups, a regioselective, successive twofold C(sp(2))-C(sp(2)) bond formation has been achieved. This straightforward catalytic process provides access to versatile products prevalent in multiple bioactive compounds and supplies a valuable functional group for subsequent transformations., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A general synthetic route to indoles from readily available anilines and epoxides by using ruthenium catalysis is described. This straightforward transformation allows a variety of indoles to be obtained in good yields by using [Ru3(CO)12]/1,1'-bis(diphenylphosphino)ferrocene as the catalytic system. Water and hydrogen are formed as the only stoichiometric by-products, making this process highly atom efficient., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An efficient procedure for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, with molecular oxygen under ambient conditions has been achieved. By applying catalytic amounts of Pd(OAc)2 in the presence of tertiary phosphine oxides (O=PR3) as ligands, a variety of substrates are selectively oxidized without formation of ester byproducts. Spectroscopic investigations and DFT calculations suggest stabilization of the active palladium(II) catalyst by phosphine oxide ligands., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Double CO inCOrporation: An atom-efficient synthesis of 4-arylfuranones from aryl halides, two molecules of CO, and terminal alkenes is reported (see scheme). 18 different 4-arylfuranones were synthesized in up to 83 % yield in a straightforward manner and with high regioselectivity. The range of the new 4-arylfuranones synthesized demonstrates the value and novelty of this procedure., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

C from CO! A straightforward procedure for the carbonylative synthesis of quinazolinones from readily available 2-aminobenzamide and aryl bromides has been developed. In the presence of a palladium catalyst, various quinazolinones were produced in moderate to excellent yields. Remarkably, no chromatography was needed for purification (see scheme).

Three COmponent -arylation: A carbonylative ketone -arylation process employing acetone for the first time, as well as acetophenones, is described (see scheme). The reaction tolerates a range of (hetero)aryl iodides and several functionalised aryl ketone coupling partners. Only low pressures of molecular CO are applied and no additional solvent is necessary.

Cute CO! An interesting and straightforward procedure for the carbonylative synthesis of chromenones from readily available salicylic aldehydes and benzyl chlorides has been developed (see scheme; DPPP = 1,3-bis(diphenylphosphino)propane). In the presence of a palladium catalyst, various coumarins were produced in good to excellent yields., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mon ami(ne)! A general and convenient methodology for 2-aminobenzoxazinone synthesis has been developed (see scheme). Readily available 2-bromoanilines and isocyanates were used as substrates and various products have been prepared in good yields. Notably, [Mo(CO)6] as a solid CO source was applied instead of gas., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Iron-catalyzed reductions: Selective iron-catalyzed reduction of aldehydes with hydrogen generated in situ by the water-gas shift reaction is presented (see scheme). The generality and selectivity of this mild procedure are demonstrated by the efficient reduction of various aromatic, aliphatic and α,β-unsaturated aldehydes., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A general and efficient method for the palladium-catalyzed carbonylative coupling of aryl iodides to benzyl acetylenes has been developed. Various furanones have been prepared in excellent yields from their corresponding benzyl acetylenes at room temperature under a CO atmosphere. For aliphatic alkynes, their corresponding alkynones were obtained in good yields. Detailed DFT calculations have also been carried out to understand the reaction pathway and the most probable reaction mechanism has been proposed., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Preparation of enols: when treated with [{Pd(cinnamyl)Cl}(2)]/cataCXium A (nBuPAd(2), Ad=adamantyl) under an atmosphere of CO, aryl ketones react with aryl halides in a carbonylative C-O coupling reaction to form (Z)-vinyl benzoates., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Oxazoline is OK! A general and efficient method for the synthesis of oxazolines has been developed. This allowed the preparation of 27 five-membered-ring heterocycles and 11 six-membered-ring heterocycles in moderate to good yields., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Flavone of the month: a general and efficient method for the palladium-catalyzed carbonylative synthesis of flavones has been developed. Starting from aryl bromides and 2-hydroxyacetophenones, the corresponding flavones have been isolated in good yields., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

(C), its (O)K! An efficient palladium-catalyzed carbonylative synthesis of 2-alkylbenzoxazinones has been developed. By starting from 2-bromoanilines and acid anhydrides, the corresponding products were isolated in good yields., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Three COming together: The first carbonylative Heck coupling reaction of aryl bromides and vinyl ethers leading to 1-aryl-3-alkoxy-2-propen-1-ones has been established (see scheme). Based on this coupling methodology, a novel one-pot synthesis of aryl-substituted pyrazoles was also realized., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

N-Cyano-N-phenyl-p-methylbenzenesulfonamide has been used as a more benign electrophilic cyanation reagent for the synthesis of various benzonitriles from (hetero)aryl bromides via formation of Grignard reagents. Electronically different and sterically demanding aryl bromides including functionalized substrates and heteroaryl bromides are successfully cyanated in good to excellent yields. The efficiency of the present methodology is shown by the expeditious syntheses of interesting pharmaceutical intermediates. Notably, chemoselective monocyanation of dibromoarenes is also achieved., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new robust palladium/phosphine catalyst system for the selective monoarylation of ammonia with different aryl bromides and chlorides has been developed. The active catalyst is formed in situ from [Pd(OAc)(2)] and air- and moisture-stable phosphines as easy-to-handle pre-catalysts. The productivity of the catalyst system is comparable to that of competitive Pd/phosphine systems; full conversion is achieved with most substrates with 1-2 mol % of Pd source and a fourfold excess of ligand (L).

Pd(OAc)2/di-1-adamantyl-n-butylphosphine (cataCXium A) is highly active in the three-component Suzuki carbonylation and represents the most general catalyst system reported up to now. A broad range of aryl/heteroaryl bromides and aryl boronic acids can be coupled to the corresponding diarylketones at low catalyst loadings.

Multicomponent reactions of aldehydes, dienophiles, and alcohols or carboxylic acid anhydrides have been developed for the first time. In situ generation of 1-acyloxy- and 1-alkoxy-1,3-butadiene derivatives in toluene in the presence of electron-deficient dienophiles provides selective and efficient access to functionalized cyclohex-2-ene-1-ols in good yields. Subsequent enzyme-catalyzed kinetic resolution gave the corresponding enantiomers with high enantioselectivity.

The acid-catalyzed condensation chemistry of simple amides and aldehydes provides a highly prolific source of diverse reactants for irreversible follow-up reactions. Amide-aldehyde mixtures have been successfully employed in multicomponent syntheses of N-acyl alpha-amino acids (via palladium-catalyzed amidocarbonylation) and various cyclohexene, cyclohexadiene, and benzene derivatives (via the amide-aldehyde-dienophile (AAD) reaction).

Based upon a highly versatile multicomponent methodology, a new one-pot synthesis of substituted phthalic acid derivatives from alpha,beta-unsaturated aldehydes was developed. The reaction involves the intermediacy of an acetamidodiene species which undergoes Diels-Alder addition to diethyl acetylenedicarboxylate. The resultant acetamidocyclohexadiene is subject to elimination of acetamide under the reaction conditions to give rise to substituted diethyl phthalates in good yields. This domino condensation-cycloaddition-elimination sequence has been applied to a variety of alpha,beta-unsaturated aldehydes. Furthermore, we demonstrated the exploitation of parallelized and automated synthesis technology for the rapid screening of reaction conditions and compositions. Detailed studies revealed the catalytic role of the employed acetamide and the occurrence of a stereoselective 1,4-syn elimination pathway under standard conditions.