This review is focused on the analysis of current data on new methods of alkenylation of arenes and heteroarenes with alkynes by transition metal catalyzed reactions, Bronsted/Lewis acid promoted ...transformations, and others. The synthetic potential, scope, limitations, and mechanistic problems of the alkenylation reactions are discussed. The insertion of an alkenyl group into aromatic and heteroaromatic rings by inter- or intramolecular ways provides a synthetic route to derivatives of styrene, stilbene, chalcone, cinnamic acid, various fused carbo- and heterocycles, etc.
Predominantly, carbon atoms of various species function as acceptors of noncovalent interactions when they are part of a π-system. Here, we report on the discovery of a halogen bond involving the ...isocyano carbon lone pair. The co-crystallization or mechanochemical liquid-assisted grinding of model mesityl isocyanide with four iodoperfluorobenezenes leads to a series of halogen-bonded adducts with isocyanides. The obtained adducts were characterized by single-crystal and powder X-ray diffraction, solid-state IR and
C NMR spectroscopies, and also by thermogravimetric analysis. The formation of the halogen bond with the isocyano group leads to a strong reduction of the isocyanide odor (3- to 46-fold gas phase concentration decrease). This manipulation makes isocyanides more suitable for laboratory storage and usage while preserving their reactivity, which is found to be similar between the adducts and the parent isocyanide in some common transformations, such as ligation to metal centers and the multi-component Ugi reaction.
► Acyclic diaminocarbenes (ADCs). ► ADC-based catalysts for organic transformations.
Starting from the first reported application of complexes bearing acyclic diaminocarbene (ADC) ligands as ...catalysts ca. 5 years ago, these compounds have been successfully employed for several useful organic transformations, viz. cross-coupling reactions (Suzuki–Miyaura, Heck, Sonogashira, Buchwald–Hartwig, and Kumada) and some cyclizations/additions to substrates having the CC and CC bonds. In these processes, ADC–metal complexes behave as an attractive alternative to extremely popular N-heterocyclic carbenes (NHCs). This review attempts to systematize studies published until now and to explain various observations and initial ideas on mechanisms and driving forces of ADC-based catalysts as well as to draw attention to the potential and the advantages that application of ADCs gives to synthetic organometallic and organic chemistry.
1,2,4-Oxadiazole is an essential motif in drug discovery represented in many experimental, investigational, and marketed drugs. This review covers synthetic methods that allow the conversion of ...different types of organic compounds into 1,2,4-oxadiazole at ambient temperature and the practical application of the latter approaches for the preparation of pharmaceutically important molecules. The discussed methods are divided into three groups. The first combines two-stage protocols requiring the preliminary preparation of
-acylamidoximes followed by cyclization under the action of organic bases. The advantages of this route are its swiftness, high efficiency of the cyclization process, and uncomplicated work-up. However, it requires the preparation and isolation of
-acylamidoximes as a separate preliminary step. The second route is a one-pot synthesis of 1,2,4-oxadiazoles directly from amidoximes and various carboxyl derivatives or aldehydes in aprotic bipolar solvents (primarily DMSO) in the presence of inorganic bases. This recently proposed pathway proved to be highly efficient in the field of medicinal chemistry. The third group of methods consists of diverse oxidative cyclizations, and these reactions have found modest application in drug design thus far. It is noteworthy that the reviewed methods allow for obtaining 1,2,4-oxadiazoles with thermosensitive functions and expand the prospects of using the oxadiazole core as an amide- or ester-like linker in the design of bioactive compounds.
A series of
-pyridyl ureas bearing 1,2,4- (
,
, and
) and 1,3,4-oxadiazole moiety (
,
,
) was prepared and characterized by HRMS,
H and
C NMR spectroscopy, as well as X-ray diffraction. The ...inspection of the crystal structures of (
-
)
,
and the Hirshfeld surface analysis made possible the recognition of the (oxadiazole)···(pyridine) and (oxadiazole)···(oxadiazole) interactions. The presence of these interactions was confirmed theoretically by DFT calculations, including NCI analysis for experimentally determined crystal structures as well as QTAIM analysis for optimized equilibrium structures. The preformed database survey allowed the verification of additional examples of relevant (oxadiazole)···π interactions both in Cambridge Structural Database and in Protein Data Bank, including the cocrystal of commercial anti-HIV drug Raltegravir.
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•Palladium-amino(hydrazido)carbene complexes as catalysts for Sonogashira reaction.•Catalytic system generates internal alkynes in 75–96% yields (TONs of up to 104).•Mechanism of the ...process proposed upon identification of key intermediates.•Catalyst deactivation is accompanied by the generation of small palladium clusters.
Metal-mediated coupling of one isocyanide in cis-PdCl2(CNR1)2 (R1=C6H11 (Cy) 1, tBu 2, 2,6-Me2C6H3 (Xyl) 3, 2-Cl-6-MeC6H34) and various carbohydrazides R2CONHNH2 R2=Ph 5, 4-ClC6H46, 3-NO2C6H47, 4-NO2C6H48, 4-CH3C6H49, 3,4-(MeO)2C6H310, naphth-1-yl 11, fur-2-yl 12, 4-NO2C6H4CH213, Cy 14, 1-(4-fluorophenyl)-5-oxopyrrolidine-3-yl 15, (pyrrolidin-1-yl)C(O) 16, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propane-1-yl 17, EtNHC(O) 18 or sulfohydrazides R3SO2NHNH2 R3=Ph 19, 4-MeC6H420 led to a series of (hydrazido)(amino)carbene complexes cis-PdCl2{C(NHNHX)N(H)R1}(CNR1); X=COR2, SO2R3(21–48, isolated yields 60–96%). All prepared species were characterized by elemental analyses (C, H, N), HR ESI+-MS, IR, 1H and 13C{1H} NMR spectroscopy, and by a single-crystal X-ray diffraction for 38. Complexes 21–48 demonstrated excellent activity as catalysts in copper-free Sonogashira coupling of aryl iodides and a variety of aromatic terminal alkynes. Catalytic system runs in environmentally benign EtOH ensuring product yields of up to 75–96% and TONs of up to 104. Mechanism of the copper-free Sonogashira catalytic cycle involving 21–48 as catalysts was proposed upon identification of key intermediates using HRESI-mass.
The
- and
-isomers of 6-(3-(3,4-dichlorophenyl)-1,2,4-oxadiazol-5-yl)cyclohex-3-ene-1-carboxylic acid (
-
and
-
) were obtained by the reaction of 3,4-dichloro-
'-hydroxybenzimidamide and
...-1,2,3,6-tetrahydrophthalic anhydride. Cocrystals of
-
with appropriate solvents (
-
‧½(1,2-DCE),
-
‧½(1,2-DBE), and
-
‧½C
H
) were grown from 1,2-dichloroethane (1,2-DCE), 1,2-dibromoethane (1,2-DBE), and a
-hexane/CHCl
mixture and then characterized by X-ray crystallography. In their structures,
-
is self-assembled to give a hybrid 2D supramolecular organic framework (SOF) formed by the cooperative action of O-H⋯O hydrogen bonding, Cl⋯O halogen bonding, and π⋯π stacking. The self-assembled
-
divides the space between the 2D SOF layers into infinite hollow tunnels incorporating solvent molecules. The energy contribution of each noncovalent interaction to the occurrence of the 2D SOF was verified by several theoretical approaches, including MEP and combined QTAIM and NCIplot analyses. The consideration of the theoretical data proved that hydrogen bonding (approx. -15.2 kcal/mol) is the most important interaction, followed by π⋯π stacking (approx. -11.1 kcal/mol); meanwhile, the contribution of halogen bonding (approx. -3.6 kcal/mol) is the smallest among these interactions. The structure of the isomeric compound
-
does not exhibit a 2D SOF architecture. It is assembled by the combined action of hydrogen bonding and π⋯π stacking, without the involvement of halogen bonds. A comparison of the
-
structures with that of
-
indicated that halogen bonding, although it has the lowest energy in
-
-based cocrystals, plays a significant role in the crystal design of the hybrid 2D SOF. The majority of the reported porous halogen-bonded organic frameworks were assembled via iodine and bromine-based contacts, while chlorine-based systems-which, in our case, are structure-directing-were unknown before this study.
A bright future: The reaction of diazomethane with acid chlorides obtained from N,N,N′,N′‐tetraalkylrhodamines affords 2‐diazo‐2,3‐dihydro‐1H‐indenespiro1,9′‐9H‐xanthen‐3‐ones—a novel class of caged ...rhodamines. These dyes allow new imaging procedures based on the step‐wise activation and detection of several fluorescent markers (see picture).
The coupling of cis-PdCl2(CNXyl)2 (Xyl = 2,6-Me2C6H3) with 4-phenylthiazol-2-amine in molar ratio 2:3 at RT in CH2Cl2 leads to binuclear (diaminocarbene)PdII complex 3c. The complex was characterized ...by HRESI+-MS, 1H NMR spectroscopy, and its structure was elucidated by single-crystal XRD. Inspection of the XRD data for 3c and for three relevant earlier obtained thiazole/thiadiazole derived binuclear diaminocarbene complexes (3a EYOVIZ; 3b: EYOWAS; 3d: EYOVOF) suggests that the structures of all these species exhibit intra-/intermolecular bifurcated chalcogen bonding (BCB). The obtained data indicate the presence of intramolecular S•••Cl chalcogen bonds in all of the structures, whereas varying of substituent in the 4th and 5th positions of the thiazaheterocyclic fragment leads to changes of the intermolecular chalcogen bonding type, viz. S•••π in 3a,b, S•••S in 3c, and S•••O in 3d. At the same time, the change of heterocyclic system (from 1,3-thiazole to 1,3,4-thiadiazole) does not affect the pattern of non-covalent interactions. Presence of such intermolecular chalcogen bonding leads to the formation of one-dimensional (1D) polymeric chains (for 3a,b), dimeric associates (for 3c), or the fixation of an acetone molecule in the hollow between two diaminocarbene complexes (for 3d) in the solid state. The Hirshfeld surface analysis for the studied X-ray structures estimated the contributions of intermolecular chalcogen bonds in crystal packing of 3a–d: S•••π (3a: 2.4%; 3b: 2.4%), S•••S (3c: less 1%), S•••O (3d: less 1%). The additionally performed DFT calculations, followed by the topological analysis of the electron density distribution within the framework of Bader’s theory (AIM method), confirm the presence of intra-/intermolecular BCB S•••Cl/S•••S in dimer of 3c taken as a model system (solid state geometry). The AIM analysis demonstrates the presence of appropriate bond critical points for these interactions and defines their strength from 0.9 to 2.8 kcal/mol indicating their attractive nature.
A new route for the synthesis of quinazolin-2,4(1
3
)-diones and thieno 2,3-
pyrimidine-2,4(1
,3
)-diones substituted by pyridyl/quinolinyl moiety in position 3 has been developed. The proposed ...method concluded in an annulation of substituted anthranilic esters or 2-aminothiophene-3-carboxylates with 1,1-dimethyl-3-(pyridin-2-yl) ureas. The process consists of the formation of
-aryl-
'-pyridyl ureas followed by their cyclocondensation into the corresponding fused heterocycles. The reaction does not require the use of metal catalysts and proceeds with moderate to good yields (up to 89%). The scope of the method is more than 30 examples, including compounds with both electron-withdrawing and electron-donating groups, as well as diverse functionalities. At the same time, strong electron-acceptor substituents in the pyridine ring of the starting ureas reduce the product yield or even prevent the cyclocondensation step. The reaction can be easily scaled to gram quantities.
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