131 research outputs found
Combined experimental and computational investigations of rhodium-catalysed C-H functionalisation of pyrazoles with alkenes
Detailed experimental and computational studies have been carried out on the oxidative coupling of the alkenes C(2)H(3)Y (Y=CO(2)Me (a), Ph (b), C(O)Me (c)) with 3-aryl-5-R-pyrazoles (R=Me (1 a), Ph (1 b), CF(3) (1 c)) using a [Rh(MeCN)(3)Cp*][PF(6)](2)/Cu(OAc)(2)â
H(2)O catalyst system. In the reaction of methyl acrylate with 1 a, up to five products (2 aaâ6 aa) were formed, including the trans monovinyl product, either complexed within a novel Cu(I) dimer (2 aa) or as the free species (3 aa), and a divinyl species (6 aa); both 3 aa and 6 aa underwent cyclisation by an aza-Michael reaction to give fused heterocycles 4 aa and 5 aa, respectively. With styrene, only trans mono- and divinylation products were observed, whereas with methyl vinyl ketone, a stronger Michael acceptor, only cyclised oxidative coupling products were formed. Density functional theory calculations were performed to characterise the different migratory insertion and ÎČ-H transfer steps implicated in the reactions of 1 a with methyl acrylate and styrene. The calculations showed a clear kinetic preference for 2,1-insertion and the formation of trans vinyl products, consistent with the experimental results
Understanding electronic effects on carboxylate-assisted C-H activation at ruthenium:the importance of kinetic and thermodynamic control
Meta-and para-substituted 1-phenylpyrazoles (R-phpyz-H) react with [RuCl2(p-cymene)]2 in the presence of NaOAc to form cyclometallated complexes [M(R-phpyz)Cl(p-cymene)] (where R = NMe2, OMe, Me, H, F, CF3 and NO2). Experimental and DFT studies indicate that product formation can be reversible or irreversible depending on the substituents and the reaction conditions. Competition experiments show that the kinetic selectivity favours electron-donating substituents and correlate well with the Hammett parameter, giving a negative slope (Ï =-2.4) that is consistent with a cationic transition state. However, surprisingly, the thermodynamic selectivity is completely opposite, with substrates featuring electron-withdrawing groups being favoured. These trends are reproduced with DFT calculations that locate a rate-limiting transition state dominated by Ru-O bond dissociation and minimal C-H bond elongation. Detailed computational analysis of these transition states shows that C-H activation proceeds by an AMLA/CMD mechanism through a synergic combination of a C-HâRu agostic interaction and C-HâŻO H-bonding. NBO calculations also highlight a syndetic bonding term, and the relative weights of these three components vary in a complementary fashion depending on the nature of the substituent. With meta-substituted ligands H/D exchange experiments signal kinetically accessible ortho-C-H activation when R = NMe2, OMe and Me. This is also modelled computationally and the calculations highlight the kinetic relevance of the HOAc/Cl exchange that occurs post C-H bond cleavage, in particular with the bulkier NMe2 and Me substituents. Our study highlights that the experimental substituent effects are dependent on the reaction conditions and so using such studies to assign the mechanism of C-H activation in either stoichiometric or catalytic reactions may be misleading.</p
Easy access to nucleophilic boron through diborane to magnesium boryl metathesis
Organoboranes are some of the most synthetically valuable and widely used intermediates in organic and pharmaceutical chemistry. Their synthesis, however, is limited by the behaviour of common boron starting materials as archetypal Lewis acids such that common routes to organoboranes rely on the reactivity of boron as an electrophile. While the realization of convenient sources of nucleophilic boryl anions would open up a wealth of opportunity for the development of new routes to organoboranes, the synthesis of current candidates is generally limited by a need for highly reducing reaction conditions. Here, we report a simple synthesis of a magnesium boryl through the heterolytic activation of the BâB bond of bis(pinacolato)diboron, which is achieved by treatment of an easily generated magnesium diboranate complex with 4-dimethylaminopyridine. The magnesium boryl is shown to act as an unambiguous nucleophile through its reactions with iodomethane, benzophenone and N,NâČ-di-isopropyl carbodiimide and by density functional theory
Mixing and matching N, N - and N, O -chelates in anionic Mg( i ) compounds: synthesis and reactivity with RN 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 C NR and CO â
Reduction of [Mg(NON)]2 ([NON]2â = [O(SiMe2NDipp)2]2â, Dipp = 2,6-iPr2C6H3) affords Mg(i) species containing NON- and NNO-ligands ([NNO]2â = [N(Dipp)SiMe2N(Dipp)SiMe2O]2â). The products of reactions with iPrNCNiPr and CO are consistent with the presence of reducing Mg(i) centres. Extraction with THF affords [K(THF)2]2[(NNO)MgâMg(NNO)] with a structurally characterised MgâMg bond that was examined using density functional theory
Remote C6-Selective Ruthenium-Catalyzed C-H Alkylation of Indole Derivatives via Ï-Activation
The
site-selective functionalization of an indole template offers
exciting possibilities for the derivatization of molecules with useful
biological properties. Herein, we report the remote C6-selective CâH
alkylation of indole derivatives enabled by dual cyclometalation/redox
ruthenium catalysis. Remote alkylation was achieved using <i>N</i>-pyrimidinyl indoles with an ancillary ester directing
group at the C3 position. This ancillary directing group proved pivotal
to reactivity at C6, with yields up to 92% achieved. A one-pot procedure
to install this directing group followed by remote C6 functionalization
has also been reported; both processes are shown to proceed via ruthenium
redox catalysis. Computationally calculated Fukui indices elucidated
that the C6 position was the most reactive vacant CâH site
toward potential functionalization. When this investigation was coupled
with deuterium incorporation studies, a C2-cyclometalation/remote
Ï-activation pathway was deduced
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C-H Functionalization Reactivity of a Nickel-Imide
This article discusses C-H functionalization reactivity of a Nickel-Imide
ĆœELJKO HOLJEVAC GOSPIÄ U VOJNOJ KRAJINI
A range of novel heterocyclic cations
have been synthesized by
the RhÂ(III)-catalyzed oxidative CâN and CâC coupling
of 1-phenylpyrazole, 2-phenylpyridine, and 2-vinylpyridine with alkynes
(4-octyne and diphenylacetylene). The reactions proceed via initial
CâH activation, alkyne insertion, and reductive coupling, and
all three of these steps are sensitive to the substrates involved
and the reaction conditions. Density functional theory (DFT) calculations
show that CâH activation can proceed via a heteroatom-directed
process that involves displacement of acetate by the neutral substrate
to form charged intermediates. This step (which leads to cationic
CâN coupled products) is therefore favored by more polar solvents.
An alternative non-directed CâH activation is also possible
that does not involve acetate displacement and so becomes favored
in low polarity solvents, leading to CâC coupled products.
Alkyne insertion is generally more favorable for diphenylacetylene
over 4-octyne, but the reverse is true of the reductive coupling step.
The diphenylacetylene moiety can also stabilize unsaturated seven-membered
rhodacycle intermediates through extra interaction with one of the
Ph substituents. With 1-phenylpyrazole this effect is sufficient to
suppress the final CâN reductive coupling. A comparison of
a series of seven-membered rhodacycles indicates the barrier to coupling
is highly sensitive to the two groups involved and follows the trend
CâN<sup>+</sup> > CâN > CâC (i.e., involving
the formation of cationic CâN, neutral CâN, and neutral
CâC coupled products, respectively)
[{SiNDipp}MgNa]2: A potent molecular reducing agent
The bimetallic species, [{SiNDipp}MgNa]2 [{SiNDipp} = {CH2SiMe2N(Dipp)}2; (Dipp = 2,6-i-Pr2C6H3)], is shown to be a potent reducing agent, able to effect one- or two-electron reduction of either dioxygen, TEMPO, anthracene, benzophenone, or diphenylacetylene. In most cases, the bimetallic reaction products imply that the dissimilar alkaline metal centers react with a level of cooperativity. EPR analysis of the benzophenone-derived reaction and the concurrent isolation of [{SiNDipp}Mg(OCPh2)2], however, illustrate that treatment with such reducible, but O-basic, species can also result in reactivity in which the metals provide independent reaction products. The notable E-stereochemistry of the diphenylacetylene reduction product prompted a computational investigation of the PhCâĄCPh addition. This analysis invokes a series of elementary steps that necessitate ring-opening via Mg+ â Na+ amido group migration of the SiNDipp ligand, providing insight into the previously observed lability of the bidentate dianion and its consequent proclivity toward macrocyclization
Azulene-Derived Fluorescent Probe for Bioimaging:Detection of Reactive Oxygen and Nitrogen Species by Two-Photon Microscopy
Two-photon fluorescence microscopy has become an indispensable technique for cellular imaging. Whereas most two-photon fluorescent probes rely on well-known fluorophores, here we report a new fluorophore for bioimaging, namely azulene. A chemodosimeter, comprising a boronate ester receptor motif conjugated to an appropriately substituted azulene, is shown to be an effective two-photon fluorescent probe for reactive oxygen species, showing good cell penetration, high selectivity for peroxynitrite, no cytotoxicity, and excellent photostability.This project has received funding from the European Unionâs Horizon 2020 research and innovation programme under the Marie SkĆodowska-Curie grant agreement No 665992 </p
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