Carbonyl Chemistry Research Articles

The ditungsten decacarbonyl dianion.

We report the synthesis and structural authentication of the ditungsten decarbonyl dianion in [(OC)5W-W(CO)5][K(18-crown-6)(THF)2]2 (1), completing the group 6 dianion triad over half a century since the area began. The W-W bond is long [3.2419(8) Å] and, surprisingly, in the solid-state the dianion adopts a D4h eclipsed rather than D4d staggered geometry, the latter of which dominates the structural chemistry of binary homobimetallic carbonyls. Computational studies at levels of theory from DFT to CCSD(T) confirm that the D4d geometry is energetically preferred in the gas-phase, being ∼18 kJ mol-1 more stable than the D4h form, since slight destabilisation of the degenerate W-CO π 5dxz and 5dyz orbitals is outweighed by greater stabilisation of the W-W σ-bond orbital. The gas-phase D4h structure displays a single imaginary vibrational mode, intrinsic reaction coordinate analysis of which links the D4h isomer directly to the D4d forms, which are produced by rotation around the W-W bond by ±45°. It is therefore concluded that the gas-phase transition state becomes a minimum on the potential energy surface when subjected to crystal packing in the solid-state.

Unusual effects of the bulky 1-norbornyl group in cobalt carbonyl chemistry: low-energy structures with agostic hydrogen atoms

Low-energy (nor)Co(CO)n (n = 3, 2) and (nor)2Co2(CO)n (nor = 1-norbornyl; n = 6, 5) structures are found to have agostic hydrogen atoms from a CH2 group adjacent to the Co–C bond forming C–H–Co bridges. In addition, low-energy structures are found with (nor)CO acyl ligands resulting from carbonyl migration.

1,3-Diphosphacyclobutadiene sandwich compounds as bidentate ligands in metal carbonyl chemistry: Binuclear chromium derivatives

The structures and thermochemistry of the binuclear 1,3-diphosphacyclobutadiene chromium carbonyl complexes (Me2C2P2)2Cr2(CO)n (n = 6, 5, 4, 3) have been examined by density functional theory. The only low-energy structure for the hexacarbonyl (Me2C2P2)2Cr2(CO)6 consists of a bidentate chelating (η4-Me2C2P2)2Cr(CO)2 sandwich diphosphine ligand bonded to a Cr(CO)4 unit with a long ∼4.0 Å Cr⋯Cr distance indicating lack of a direct metal-metal bond. The lowest energy structure for the pentacarbonyl (Me2C2P2)2Cr2(CO)5 is a triplet structure derived from this singlet hexacarbonyl structure by loss of a CO group from the sandwiched chromium atom. The bridging η1,4-Me2C2P2 ligands found in these two structures, using the four π-electrons of the P2C2 ring to bond to one chromium atom and a phosphorus lone pair to bond to the other chromium atom but not sandwiching a chromium atom, are features of the next lowest energy triplet and singlet (Me2C2P2)2Cr2(CO)5 structures. In contrast to the hexa- and pentacarbonyls, the lowest energy structures of the more highly unsaturated tetra- and tricarbonyls (Me2C2P2)2Cr2(CO)n (n = 4, 3) have terminal tetrahapto η4-Me2C2P2 rings and chromium-chromium multiple bonds.

COtab: Expedient and Safe Setup for Pd-Catalyzed Carbonylation Chemistry.

Bench-stable tablets (COtabs) have been developed for the rapid and safe production of carbon monoxide. The tablets can be made in less than 5 min without the use of a glovebox and only require a stock solution of an amine base to liberate a specific quantity of CO in a two-chamber system. The COtabs were tested in five different carbonylation reactions and provided similar yields compared to literature procedures. Finally, a gram-scale reaction was conducted, as well as 13C-isotope labeling of the anticancer drug, olaparib.

Alkynes as Synthetic Equivalents of Ketones and Aldehydes: A Hidden Entry into Carbonyl Chemistry.

The high energy packed in alkyne functional group makes alkyne reactions highly thermodynamically favorable and generally irreversible. Furthermore, the presence of two orthogonal π-bonds that can be manipulated separately enables flexible synthetic cascades stemming from alkynes. Behind these “obvious” traits, there are other more subtle, often concealed aspects of this functional group’s appeal. This review is focused on yet another interesting but underappreciated alkyne feature: the fact that the CC alkyne unit has the same oxidation state as the -CH2C(O)- unit of a typical carbonyl compound. Thus, “classic carbonyl chemistry” can be accessed through alkynes, and new transformations can be engineered by unmasking the hidden carbonyl nature of alkynes. The goal of this review is to illustrate the advantages of using alkynes as an entry point to carbonyl reactions while highlighting reports from the literature where, sometimes without full appreciation, the concept of using alkynes as a hidden entry into carbonyl chemistry has been applied.

Efficient synthesis of carbon-11 labelled acylsulfonamides using [11C]CO carbonylation chemistry.

Herein, a novel method for carbon-11 labeling of acyl sulfonamides by a one-step insertive [11C]CO carbonylative cross-coupling reaction between aryl halides and sulfonamides is presented. Various model compounds as well as drug molecules LY573636 (tasisulam) and ABT-199 were obtained in excellent yields. This method provides a valuable and widely applicable contribution to the continuously expanding radiochemical toolbox for PET research.

Coupling of fluoroborylene ligands in manganese carbonyl chemistry to give a difluorodiborene ligand

A bridging difluorodiborene μ-B2F2 ligand has been observed in two of the three lowest energy Mn2(BF)2(CO)7 structures as well as in the lowest energy Mn2(BF)2(CO)6 structure.

New Directions in Transition Metal Catalyzed Carbonylation Chemistry.

Carbon monoxide (CO) represents an important C1-building block for the construction of some of the most fundamental chemical functionalities carrying a carbon-oxygen double bond. Transition metal catalysis plays a key role in promoting such transformations. We have earlier shown that the combination of palladium catalysis with CO releasing molecules and the two-chamber reactor, COware, provides a convenient and safe means for performing traditional Pd-catalyzed carbonylative couplings, as well as being a platform for the discovery of new carbonylation reactions. Furthermore, the method can be adapted to 13C- and 14C-isotope labeling, as well as providing for a suitable setting for developing efficient carbonylation reactions with 11CO. Herein, we provide a short overview of our latest findings in this area with emphasis on carbonylative couplings with fluorinated building blocks, but also discuss our efforts to develop viable Ni-catalyzed carbonylations with aliphatic substrates, which can be performed efficiently under low CO partial pressures.

Cover Feature: Visible-Light-Driven Reduction of CO2 to CO and Its Subsequent Valorization in Carbonylation Chemistry and 13 C Isotope Labeling (ChemPhotoChem 8/2018)

Cover Feature: Visible-Light-Driven Reduction of CO₂ to CO and Its Subsequent Valorization in Carbonylation Chemistry and ¹³ C Isotope Labeling (ChemPhotoChem 8/2018)

A Low-Valent Molybdenum Nitride Complex: Reduction Promotes Carbonylation Chemistry.

Toward nitrogen functionalization, reactive terminal transition metal nitrides with high d-electron counts are of interest. A series of terminal MoIV nitride complexes were prepared within the context of exploring nitride/carbonyl coupling to cyanate. Reduction affords the first MoII nitrido complex, an early metal nitride with four valence d-electrons. The binding mode of the para-terphenyl diphosphine ancillary ligand changes to stabilize an electronic configuration with a high electron count and a formal M-N bond order of three. Even with an intact Mo≡N bond, this low-valent nitrido complex proves to be highly reactive, readily undergoing N-atom transfer upon addition of CO, releasing cyanate anion.

Recent developments in carbonylation chemistry using [13 C]CO, [11 C]CO, and [14 C]CO.

Carbon monoxide represents the most important C1-building block for the chemical industry, both for the production of bulk and fine chemicals, but also for synthetic fuels. Yet its toxicity and subsequently its cautious handling have limited its applications in medicinal chemistry research and in particular for the synthesis of pharmaceutically relevant molecules. Recent years have nevertheless witnessed a considerable headway on the development of carbon monoxide surrogates and reactor systems, which provide an ideal setting for performing carbonylation chemistry with stoichiometric and substoichiometric carbon monoxide. Such setups are particularly ideal for the introduction of isotope labels such as carbon-11, carbon-13, and carbon-14 into bioactive compounds. This review summarizes this growing field and examines the large number of carbonylation reactions that can be exploited for the introduction of a carbon isotope.

Visible‐Light‐Driven Reduction of CO2 to CO and Its Subsequent Valorization in Carbonylation Chemistry and 13C Isotope Labeling

AbstractA convenient and safe approach in valorizing carbon monoxide (CO) produced from the photocatalytic reduction of carbon dioxide (CO2) has been investigated. Visible light was used to drive an optimized photocatalytic reduction using a ruthenium trisbipyridine complex as a sensitizer and a rhenium bipyridyl carbonyl complex as a catalyst to perform an efficient reduction of CO2 to CO, which was then simultaneously utilized in a palladium‐catalyzed aminocarbonylation reaction at room temperature. This approach provides safe handling of the produced CO which also opens the way for a more efficient application of 13C‐isotope and 14C‐radioisotope‐labeled CO2 in pharmaceutically relevant drug labeling.

Metastatic melanoma imaging using a novel Tc-99m-labeled lactam-cyclized alpha-MSH peptide

The purpose of this study was to determine the metastatic melanoma imaging property of 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}. HYNIC-Aoc-Nle-CycMSHhex was synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The IC50 value of HYNIC-Aoc-Nle-CycMSHhex was 0.78 ± 0.13 nM for B16/F10 melanoma cells. 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex displayed significantly higher uptake (14.26 ± 2.74 and 10.45 ± 2.31% ID/g) in B16/F10 metastatic melanoma-bearing lung than that in normal lung (0.90 ± 0.15 and 0.53 ± 0.14% ID/g) at 2 and 4 h post-injection, respectively. B16/F10 pulmonary metastatic melanoma lesions were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex as an imaging probe at 2 h post-injection, underscoring its potential as an imaging probe for metastatic melanoma detection.

One-Pot Synthesis of Polypyrazoles by Click Reactions

AbastractWe developed an efficient one-pot metal-free click polymerization procedure for the synthesis of 3,5-disubstituted polypyrazoles with high yields, high molecular weights, and narrow molecular weight distribution. The method involved two click reactions in a one-pot synthesis. The first reaction was the carbonyl chemistry of “non-aldol” type (condensation reaction of aldehydes with p-toluenesulfonylhydrazide), and the second was a click polymerization reaction of diazo compounds with alkynes. The reactions occurred sequentially by adding the reactants step by step. The diazo compound needed for the second click reaction was generated in situ by the first click reaction. The structures of the polypyrazoles were characterized by IR and 1H NMR analyses. And their thermal properties and solubility were also tested.

Scalable carbon dioxide electroreduction coupled to carbonylation chemistry

Significant efforts have been devoted over the last few years to develop efficient molecular electrocatalysts for the electrochemical reduction of carbon dioxide to carbon monoxide, the latter being an industrially important feedstock for the synthesis of bulk and fine chemicals. Whereas these efforts primarily focus on this formal oxygen abstraction step, there are no reports on the exploitation of the chemistry for scalable applications in carbonylation reactions. Here we describe the design and application of an inexpensive and user-friendly electrochemical set-up combined with the two-chamber technology for performing Pd-catalysed carbonylation reactions including amino- and alkoxycarbonylations, as well as carbonylative Sonogashira and Suzuki couplings with near stoichiometric carbon monoxide. The combined two-reaction process allows for milligram to gram synthesis of pharmaceutically relevant compounds. Moreover, this technology can be adapted to the use of atmospheric carbon dioxide.

Carbonylation as a novel method for the assembly of pyrazine based oligoamide alpha-helix mimetics.

The design and synthesis of oligoamide α-helix peptidomimetics is reported. The oligoamide type systems are prepared in a modular fashion by coupling the monomers using palladium-catalyzed carbonylation chemistry. This enabled us to use substrates with a low nucleophilicity, leading to previously unreported pyrazine based oligoamide α-helix mimetics. The proof of principle is given by synthesizing a small set of compounds. Various end-capping groups were introduced and also a mixed multimer was successfully prepared.

Substrate-Induced Carbon Monoxide Reactivity Suggests Multiple Enzyme Conformations at the Catalytic Copper M-Center of Peptidylglycine Monooxygenase.

The present study uses CO as a surrogate for oxygen to probe how substrate binding triggers oxygen activation in peptidylglycine monooygenase (PHM). Infrared stretching frequencies (ν(C ≡ O)) of the carbonyl (CO) adducts of copper proteins are sensitive markers of Cu(I) coordination and are useful in probing oxygen reactivity because the electronic properties of O2 and CO are similar. The carbonyl chemistry has been explored using PHM WT and a number of active site variants in the absence and presence of peptidyl substrates. We have determined that upon carbonylation (i) a major CO band at 2092 cm-1 and a second minor CO band at 2063 cm-1 are observed in the absence of peptide substrate Ac-YVG; (ii) the presence of peptide substrate amplifies the minor CO band and causes it to partially interconvert with the CO band at 2092 cm-1; (iii) the substrate-induced CO band is associated with a second conformer at CuM; and (iv) the CuH-site mutants, which are inactive, fail to generate any substrate-induced CO bands. The total intensity of both bands is constant, suggesting that the Cu(I)M-site partitions between the two carbonylated enzyme states. Together, these data provide evidence for two conformers at CuM, one of which is induced by binding of the peptide substrate with the implication that this represents the conformation that also allows binding and activation of O2.

Troels Skrydstrup

Angewandte Chemie International EditionVolume 56, Issue 18 p. 4914-4914 Author ProfileFree Access Troels Skrydstrup First published: 28 October 2016 https://doi.org/10.1002/anie.201610024AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract “My favorite place on earth is at home, especially after finishing a trip. I chose chemistry as a career because of an inspiring chemistry teacher in first-year chemistry at Queen's University. ...” This and more about Troels Skrydstrup can be found on page 4914. Troels Skrydstrup The author presented on this page has recently published his 10th article in Angewandte Chemie in the last 10 years: “Direct Access to α,α-Difluoroacylated Arenes by Palladium-Catalyzed Carbonylation of (Hetero)Aryl Boronic Acid Derivatives”: T. L. Andersen, M. W. Frederiksen, K. Domino, T. Skrydstrup, Angew. Chem. Int. Ed. 2016, 55, 10396; Angew. Chem. 2016, 128, 10552. Date of birth: April 15, 1961 Position: Professor of Organic Chemistry, Aarhus University E-mail: ts@chem.au.dk Homepage: http://www.skrydstrup-group.com/ Education: 1983 BSc (Eng), Queen's University, Kingston, Ontario 1985 MSc (Eng), The Technical University of Denmark 1988 PhD with Anders Kjær, The Technical University of Denmark 1988–1989 postdoctoral work with Guy Ourisson, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette 1989—1990 postdoctoral work with Klaus Bock, The Carlsberg Laboratory, Copenhagen 1990–1992 postdoctoral work with David Grierson, Institut de Chimie des Substances Naturelles Awards: 2002 Torkil Holm Research Award for Chemistry, Danish Academy for Technical Sciences (ATV); 2008 elected to the Royal Danish Academy of Sciences; 2012 Danish knighthood Current research interests: Transition-metal catalysis; reactor design; cross-coupling reactions; isotopic labeling; PET chemistry; mechanistic investigations Hobbies: Road biking, playing the guitar (bluegrass, blues, …) My favorite place on earth is at home, especially after finishing a trip. I chose chemistry as a career because of an inspiring chemistry teacher in first-year chemistry at Queen's University. If I could have dinner with three famous scientists from history, they would be Niels Bohr, Marie Curie, and Albert Einstein (true heroes of modern science!). The most important thing I learned from my parents is to spend time with your children and show an interest in what they do. I learned this the hard way as a child. My not-so-secret passion is chocolate, especially from a “haute chocolaterie” from Belgium! I lose track of time when we have discussions about new research projects. It is always so exciting! The best advice I have ever been given is to be patient, although it can be hard sometimes. I would have liked to have discovered cycloaddition reactions. Such cool transformations for carbon—carbon coupling in synthetic organic chemistry. Cross coupling reactions are not bad either! What I look for first in a publication is the applicability of the science. I like to read papers whereby the science provides solutions for real-life problems. My 5 top papers: References 1“A Highly Stereoselective Route to 1,2-trans-C-Glycosides via Glycosyl Samarium(III) Reagents”: D. Mazéas, T. Skrydstrup, J.-M. Beau, Angew. Chem. Int. Ed. 1995, 34, 909; Angew. Chem. 1995, 107, 990. (Generation of stable organosamarium reagents at the anomeric position of hexoses.) 2“Heck Coupling with Nonactivated Alkenyl Tosylates and Phosphates. Examples of Effective 1,2-Migrations of the Alkenyl Palladium(II) Intermediates”: A. L. Hansen, J.-P. Ebran, M. Ahlquist, P.-O. Norrby, T. Skrydstrup, Angew. Chem. Int. Ed. 2006, 45, 3349; Angew. Chem. 2006, 118, 3427. (An unusual rearrangement in the Heck coupling.) 3“In Situ Generated Bulky Palladium Hydride Complexes as Catalysts for the Efficient Isomerization of Olefins. Selective Transformation of Terminal Alkenes to 2-Alkenes”: D. Gauthier, A. T. Lindhardt, E. P. K. Olsen, J. Overgaard, T. Skrydstrup, J. Am. Chem. Soc. 2010, 132, 7998. (The title complex can selectively promote one-carbon migrations of terminal olefins.) 4“Ex Situ Generation of Stoichiometric and Substoichiometric 12CO and 13CO and its Efficient Incorporation in Palladium-Catalyzed Aminocarbonylations”: P. Hermange, A. T. Lindhardt, R. Taaning, K. Bjerglund, D. Lupp, T. Skrydstrup, J. Am. Chem. Soc. 2011, 133, 6061. (Our first work with two-chamber reactors in combination with a CO-releasing molecule for carbonylation chemistry.) 5“Efficient Fluoride-Catalyzed Conversion of CO2 to CO at Room Temperature”: C. Lescot, D. U. Nielsen, I. Marakov, A. T. Lindhardt, K. Daasbjerg, T. Skrydstrup, J. Am. Chem. Soc. 2014, 136, 6142. (CO2 reduction coupled to our two- and three-chamber reactors for the synthesis of pharmaceuticals.) Volume56, Issue18April 24, 2017Pages 4914-4914 ReferencesRelatedInformation

ChemInform Abstract: Visible Light‐Induced Carbonylation Reactions with Organic Dyes as the Photosensitizers

AbstractReview: [15 refs.

Visible Light‐Induced Carbonylation Reactions with Organic Dyes as the Photosensitizers

Dyes can CO do it: Organic dyes and pigments are usually applied in textile dyeing, which can be dated back to the Neolithic period. Interestingly, the possibility to use organic dyes as photoredox catalysts has also been noticed by organic chemists and applied in organic synthesis. Carbonylation reactions as a powerful procedure in carbonyl-containing compound preparation have also been studied. In this manuscript, the recent achievements in using organic dyes as visible-light sensitizers in carbonylation chemistry are summarized and discussed.