Pd(II)-Catalyzed C-H Acylation of (Hetero)arenes. Recent Advances

Di(hetero)aryl ketones are important motifs present in natural products, pharmaceuticals or agrochemicals. In recent years, Pd(II)-catalyzed acylation of (hetero)arenes in the presence of an oxidant has emerged as a catalytic alternative to classical acylation methods, reducing the production of toxic metal waste. Different directing groups and acyl sources are being studied for this purpose, although further development is required to face mainly selectivity problems in order to be applied in the synthesis of more complex molecules. Selected recent developments and applications are covered in this review.This work is supported by Ministerio de Economía y Competitividad (CTQ2016-74881-P), Ministerio de Ciencia e Innovación (PID2019-104148GB-I00) and Gobierno Vasco (IT1045-16)

Heterocalixarenes part 4. Synthesis of oxocalix [1] heterocycle [2]-arenes: a unique H-bonding network in calix [1] benzimidazol-2-one [2] arene &#189; H<SUB>2</SUB>O

The Friedel.Crafts aroylation of 2-methylanisole with 3-methylbenzoyl chloride followed by NBS bromination and cyclizations with 1,3-dihydrobenzimidazol-2-one, 1,3-dihydro-5,6-dinitrobenzimidazol-2-one, uracil, 6-methyluracil and quinazoline-2,4(1H,3H)-dione provide respective oxocalix[1]heterocycle[2]arenes 5.9. The X-ray crystal structure (solid) and 1H NMR spectral (solution) studies show them to have by and large inwardly flattened partial cone conformations which vary in torsion angles between the rings. The calix[1]benzimidazol-2-one[2]arene &#189; H2O complex shows a unique array of H-bonds in which three of the four CH and the imide oxygen of the benzimidazol-2-one unit, carbonyl oxygen and water molecule are involved in H-bonding with surrounding calixarene molecules. This heterocalixarene, in contrast to earlier reported benzimidazol-2-one-based calixarenes, does not show heterocyclic &#960;-&#960; stacking

Deproto-metallation using mixed lithium-zinc and lithium-copper bases and computed CH acidity of 2-substituted quinolines

International audience2-Substituted quinolines were synthesized, and their deproto-metallation using the bases prepared by mixing LiTMP with either ZnCl2*TMEDA (1/3 equiv) or CuCl (1/2 equiv) was studied. With phenyl and 2-naphthyl substituents, the reaction occurred at the 8 position of the quinoline ring, affording the corresponding iodo derivatives or 2-chlorophenyl ketones using the lithium-zinc or the lithium-copper combination, respectively. With a 4-anisyl substituent, a dideprotonation at the 8 and 3' position was noted using the lithium-zinc base. With 3-pyridyl, 2-furyl and 2-thienyl substituents, the reaction took place on the subtituent, at a position adjacent to its heteroatom. 2-Chlorophenyl 2-phenyl-8-quinolyl ketone could be cyclized under palladium catalysis. The experimental results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method

(2,7-Dimethoxy­naphthalene-1,8-di­yl)bis­(4-fluoro­benzo­yl)dimethanone

The title compound, C26H18F2O4, is a naphthalene derivative in which the two aroyl groups at the 1- and 8-positions (peri positions) are anti to each other. There is an appreciable difference in the dihedral angles between the naphthalene ring system and the two benzene rings [66.88 (7)° and 88.09 (6)°]. In the crystal, weak C—H⋯O inter­actions involving one of the carbonyl groups and an aromatic C—H group ortho to the F atom seem to stabilize the packing of the mol­ecules

Late-Stage C-H Acylation of Tyrosine-Containing Oligopeptides with Alcohols

The selective tagging of amino acids within a peptide framework while using atom-economical C-H counterparts poses an unmet challenge within peptide chemistry. Herein, we report a novel Pd-catalyzed late-stage C-H acylation of a collection of Tyr-containing peptides with alcohols. This water-compatible labeling technique is distinguished by its reliable scalability and features the use of ethanol as a renewable feedstock for the assembly of a variety of peptidomimetics.The authors are grateful to the Ministerio de Ciencia e Innovacion (RTI2018-093721-B-I00, MCI/AEI/FEDER, UE) and the Basque Government (IT1033-16) for financial support. The authors thank the technical and human support provided by the Central Service of Analysis-SGIker of UPV/EHU and European funding (ERDF and ESF). In~aki Urruzuno thanks UPV/EHU for the postdoctoral research grant (EspDoc2020

Heterocalixarenes. Part 3: Bis-oxo-bridged calix[1]cyclicurea[3]arene and calix[1]cyclicurea[1]pyridine[2]arenes. Synthesis, X-Ray crystal structure and conformational analysis

The Friedel-Crafts aroylations of 2- and 4-methylanisole with isophthaloyl dichloride or pyridine-2,6-dicarbonyl dichloride provide respective diones, which on bromination with NBS provide corresponding bisbromomethyl derivatives that undergo simple cyclocondensations with embedded cyclicurea-containing heterocycles, viz. benzimidazol-2(1H)-one, 5-nitrobenzimidazol-2(1H)-one, 5,6-dinitrobenzimidazol-2(1H)-one, uracil and quinazoline-2,4(1H,3H)-dione to form 11 new bis-oxo-bridged heterocalix[4]arenes ( 11-19, 24, 25). The X-ray crystal structure of the 11-benzene complex, 1H-1H COSY spectra and energy-minimization studies assign partial cone conformations to these heterocalix[4]arenes. The variation in the cyclicurea moiety controls the flexibility of these heterocalix[4]arenes

Chemistry of Cyclic Ketene-N,O-Acetals

A cyclic ketene acetal is an olefin that is substituted at one end by two electrondonating hetero atoms, like O, N, S, where these heteroatoms are connected together by a chain. Delocalization of the lone pair electrons of the two hetero atoms to the double bond makes the β-carbon (the exocyclic methylene carbon) electron rich and nucleophilic. A major goal of cyclic ketene acetal chemistry is to provide functionalized cyclic ketene acetal monomers as precursors to polymers of desired properties. The cyclic ketene-N,O-acetal 3-methyl-2-methylene-oxazolidine, generated in situ from 2-methyl-2-oxazolinium iodide and triethylamine, reacted with aryl isocyanates in refluxing THF to give α,α-bis(N-arylamido) lactams via the iodide-catalyzed rearrangement of β,β–bis(N-arylamido) cyclic ketene-N,O-acetal intermediates. However, similar β,β–bis(N-arylamido) cyclic ketene-N,O-acetals having two methyl substituents at C-4, did not rearrange due to hindrance of the iodide attack on C-5. 3,4,4-Trimethyl-2-methylene-oxazolidine reacted with aryl chloroformates to form both mono- and di-aryloxycarbonylation adducts. The two methyl groups at C-4 Template Created By: Damen Peterson 2009 hindered the alternative polymerization route. 3-Methyl-2-methylene-oxazolidine, which does not have two methyl groups at C-4, underwent cationic polymerization under identical conditions. Benzoylation of 2-methyl-2-oxazoline with benzoyl chloride gave a ring-opened N,C,O-trisbenzoylation product via O-benzoylation of the N,C-bisbenzoylated intermediate, followed by chloride attack on C-5. The N,C,O-trisbenzoylated product underwent N,O-double debenzoylation by KOH to give the cyclic ketene-N,O-acetal, 2- oxazolidin-2-ylidene-1-phenylethanone. This compound (an ambident nucleophile), upon deprotonation, reacted with benzoyl chloride to give the β,β-bisbenzoylated cyclic ketene-N,O-acetal, and reacted with phenyl chloroformate to give a novel heterocycle, [1,3]oxazine-2,4-dione. The benzoylation of 2-methyl-2-oxazine gave a similar ringopened N,C,O-trisbenzoylation product. Reactions of 2-methyl-2-oxazoline, 2,4,4-trimethyl-2-oxazoline and 2-methyl-2- thiazoline with trifluoroacetyl anhydride gave C-trifluoroacetylated cyclic ketene-N,O(S)- acetals. However, trifluoroacetylation of 2-methyl-2-oxazine gave the β,β- bistrifluoroacetylated cyclic ketene-N,O-acetal. In summary, a novel iodide-catalyzed rearrangement of β,β–bis(N- arylamido)- cyclic ketene-N,O-acetals was found. The [1,3]oxazine-2,4-dione heterocycle synthesized during this research also demonstrates the synthetic potential of cyclic ketene acetal chemistry in pharmaceutical industry. Functionalization of cyclic ketene acetals based on the chemistry developed in this work will find applications in polymer industry

The synthesis of furanones via rhodium-catalyzed carbonylative addition reactions of arylboronic acids to alkynes

Thesis (Master)--İzmir Institute of Technology, Chemistry, İzmir, 2008Includes bibliographical references (leaves: 65-73)Text in English; Abstract: Turkish and Englishxii, 242 leavesThis study reveals that 5-Aryl-2(5H)-furanones can be synthesized by rhodiumcatalyzed reaction of arylboronic acids with internal alkynes under a CO atmosphere.In this thesis, relatively mild and simple method for synthesis of 2(5H)-furanones was developed. Our method was found to be applicable for various arylboronic acids and alkynes.The methodology of this study is well applicable for ortho-, para- and metasubstituted phenylboronic acids. But slightly higher yields were obtained with parasubstituted phenylboronic acids than ortho- or meta- substituted ones.It was found that when an asymmetric alkyne is used under the optimized conditions, aroylation occurs more on the electron deficient acetylenic carbon as compared with electron rich acetylene when aroylrhodium(I) species undergoes 1,2-addition to the carbon-carbon triple bond in the reaction. That affects the ratio of isomeric yields of furanones which were produced in the reactions of asymmetric alkynes with phenylboronic acid.2(5H)-Furanones that we synthesized can be used in many areas such as food manufacturing, perfume and medicinal industries

A Palladium-Catalyzed 4CzIPN-Mediated Decarboxylative Acylation Reaction of O-Methyl Ketoximes with α-Keto Acids under Visible Light.

This work presents a palladium-catalyzed oxime ether-directed ortho-selective benzoylation using benzoylformic acid as the acyl source with a palladium catalyst and 4CzIPN as the co-catalyst under light. Various non-symmetric benzophenone derivatives were obtained in moderate to good yields. A preliminary mechanism study revealed that the reaction proceeds through a free radical pathway

Site-Selective C - H Functionalization of Amino Acids and Peptides Upon Radical Chemistry

224 p.El objetivo de esta Tesis Doctoral ha sido desarrollar nuevas metodologías de modificación selectiva decompuestos peptídicos. Por un lado, hemos estudiado metales alternativos como el cobalto para lamodificación C-H selectiva de N-aril glicinas mediante procesos CDC (Cross-DehydrogenativeCoupling). Por otra parte, también hemos desarrollado nuevas metodologías para la diversificación deenlaces C ¿ H de aminoácidos con ramificaciones aromáticas como la fenilalanina (Phe) y tirosina (Tyr).Para ello se introdujeron grupos directores exógenos de tipo piridina en las estructuras peptídicas quepermitieron llevar a cabo la acilación selectiva de enlaces C-H con aldehídos mediante procesosradicalarios en presencia de catalizadores de paladio. Esta aproximación sintética ofrece múltiplesventajas frente a métodos más convencionales, donde generalmente se requieren sustratosprefuncionalizados y la generación de residuos halogenados es inevitable