Arylation Of Sp3 Research Articles

Iridium(III) complexes with cyclometalated imidazolylidene ligands: sp2 phenyl C[sbnd]H activation vs sp2 benzyl C[sbnd]H activation and catalytic transfer hydrogenation reactions

Cyclometalated N-heterocyclic carbene (NHC) complexes possess fascinating electronic and catalytic properties. A series of cyclometalated iridium(III) complexes have been synthesized from the corresponding imidazolium salts via the aryl sp2 CH bond activation at the N1-phenyl/N3-benzyl wingtips of the imidazolylidene moiety. The electronic tuning towards the competitive formation of cyclometalated complexes (sp2 phenyl CH activation vs sp2 benzyl CH activation) has been discussed. These complexes have been utilized for the transfer hydrogenation (TH) reaction of 4-bromobenzaldehyde and 4-bromoacetophenone. These complexes showed excellent yields of the aryl-alcohols from 4-bromobenzaldehyde or 4-bromoacetophenone.

Mono and di ortho-C-H acetoxylation of 2-aryloxyquinoline-3-carbaldehydes.

2-Aryloxyquinolines are well known for various biological activities. In this report, we have developed a novel protocol for introducing an acetoxy functional group on the aryl sp2 carbon of 2-aryloxyquinoline-3-carbaldehyde using a palladium catalyst for the first time. Interestingly, this C-H acetoxylation reaction is highly chemo- and site-selective. By modifying the reaction conditions, mono or di ortho-C-H acetoxylation products have been synthesized selectively with good yields and with good functional group tolerance.

Electrochemical 1,2‐Diarylation of Alkenes Enabled by Direct Dual C–H Functionalizations of Electron‐Rich Aromatic Hydrocarbons

A cobalt-promoted electrochemical 1,2-diarylation of alkenes with electron-rich aromatic hydrocarbons via direct dual C-H functionalizations is described, which employs a radical relay strategy to produce polyaryl-functionalized alkanes. Simply by using graphite rod cathode instead of platinum plate cathode, chemoselectivity of this radical relay strategy is shifted to the dehydrogenative [2+2+2] cycloaddition via 1,2-diarylation, annulation, and dehydrogenation cascades leading to complex 11,12-dihydroindolo[2,3-a]carbazoles. Mechanistical studies indicate that a key step for the radical relay processes is transformations of the aromatic hydrocarbons to the aryl sp2 -hybridized carbon-centered radicals via deprotonation of the corresponding aryl radical cation intermediates with bases.

Visible Light-Induced Oxidative Chlorination of Alkyl sp3 C-H Bonds with NaCl/Oxone at Room Temperature.

A visible light-induced monochlorination of cyclohexane with sodium chloride (5:1) has been successfully accomplished to afford chlorocyclohexane in excellent yield by using Oxone as the oxidant in H2O/CF3CH2OH at room temperature. Other secondary and primary alkyl sp3 C-H bonds of cycloalkanes and functional branch/linear alkanes can also be chlorinated, respectively, under similar conditions. The selection of a suitable organic solvent is crucial in these efficient radical chlorinations of alkanes in two-phase solutions. It is studied further by the achievement of high chemoselectivity in the chlorination of the benzyl sp3 C-H bond or the aryl sp2 C-H bond of toluene.

Iron and Manganese Catalysts for the Selective Functionalization of Arene C(sp2)−H Bonds by Carbene Insertion

AbstractThe first examples of the direct functionalization of non‐activated aryl sp2 C−H bonds with ethyl diazoacetate (N2CHCO2Et) catalyzed by Mn‐ or Fe‐based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are FeII or MnII complexes bearing the tetradentate pytacn ligand (pytacn= 1‐(2‐pyridylmethyl)‐4,7‐dimethyl‐1,4,7‐triazacyclononane). When using alkylbenzenes, the alkylic C(sp3)−H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp2 C−H bonds.

ChemInform Abstract: Intermolecular Oxidative C—N Bond Formation under Metal‐Free Conditions: Control of Chemoselectivity Between Aryl sp2 and Benzylic sp3 C—H Bond Imidation.

AbstractArenes undergo efficient imidation in the presence of Ph‐I(OAc)2.

Direct Benzylic Alkylation via Ni-Catalyzed Selective Benzylic sp3 C−O Activation

This article demonstrates the first cross coupling of benzyl ether with Grignard reagents via Ni-catalyzed benzylic sp3 C−O activation with high efficiency and excellent chemoselectivity. Benzylic sp3 C−O and aryl sp2 C−O were differentiated, controlled by ligands.

Direct Arylation of Aryl(azaaryl)methanes

The authors report a new repertoire of direct arylation of sp3 C-H bonds and direct arylation of diarylmethanes providing triarylmethanes. Treatment of chlorobenzene with 2-benzylpyrimidine in the presence of cesium hydroxide under PdCl2/tricyclohexylphosphine (PCy3) catalysis in refluxing xylene provided 2-(diphenylmethyl)pyrimidine in high yield. A variety of aryl chlorides underwent the arylation reaction. Unfortunately, attempted reactions of electron-deficient azaarylmethanes resulted in incomplete conversions.

Palladium‐Catalyzed Methylation and Arylation of sp2 and sp3 C—H Bonds in Simple Carboxylic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Multinuclear NMR studies and ab initio structure calculations of hindered phencyclone diels‐alder adducts from symmetrical cyclic dienophiles: Cyclohexene, vinylene carbonate, vinylene trithiocarbonate and two N‐aryl maleimides

AbstractA series of hindered Diels‐Alder adducts have been prepared from phencyclone, 1, with various unusual symmetrical cyclic dienophiles, including cyclohexene, 2a; vinylene carbonate, 2b; vinylene trithiocarbonate, 2c; and the N‐aryl maleimides: N‐(4‐dimethylamino‐3,5‐dinitrophenyl)maleimide (“Tuppy's maleimide”), 2d; and N‐[3,5‐bis(trifluoromethyl)phenyl]maleimide, 2e. The highly hindered adducts, 3a‐e, respectively, were extensively characterized by one‐ and two‐dimensional NMR methods, observing proton, carbon‐13 and fluorine‐19. High resolution COSY45 spectra permitted rigorous proton NMR assignments. The 2D heteronuclear C‐H chemical shift correlation spectra (HETCOR, XHCORR) were obtained for adducts 3a‐d, allowing specific assignments for protonated carbons. Corrections to earlier proton NMR assignments for the vinylene carbonate adduct are given; results of the gated decoupling 13C NMR experiment for this adduct supported endo adduct stereochemistry. Relative proton chemical shifts for bridgehead phenyls of adduct 3c appeared anomalous relative to other adducts, suggesting possible special anisotropic interactions (with endocyclic sulfur or other anisotropic groups in the product) due to the unusual calculated orientation of the phenyls. The unsubstituted bridgehead phenyls in all adducts were shown to exhibit slow exchange limit (SEL) 1H and 13C spectra on the NMR timescales at ambient temperatures (7 tesla) showing slow rotations about the C(sp3)‐C(aryl sp2) bonds. The rapid rotation of the N‐aryl rings of the maleimide adducts was indicated by fast exchange limit spectra, suggesting that ortho substitution of the N‐aryl ring may be necessary to slow this rotation to the SEL regime. Ab initio geometry optimizations at the Hartree‐Fock level were carried out for each adduct, with the 6‐31G* basis sets. Appreciable geometry differences were seen in calculated structures, and significant NMR chemical shift differences were experimentally observed, depending on the nature of the groups attached to the (Z)‐HC=CH moiety of the dienophiles.

Selective and Catalytic Arylation of N-Phenylpyrrolidine: sp3 C−H Bond Functionalization in the Absence of a Directing Group

We herein describe our studies on arylation of N-phenylpyrrolidine, which led to the development of a new transformation for the direct and selective arylation of sp3 C-H bonds in the absence of a directing group. In this method, Ru(H)2(CO)(PCy3)3 4 was used as the catalyst, and preliminary mechanistic studies suggested that Ru(Ph)(I)(CO)(PCy3)2 5 is the key intermediate of the catalytic cycle. A large kinetic isotope effect (kH/kD = 5.4) was observed, which supports the proposal that C-H bond metalation is the slow step. Preliminary examination of the substrate scope showed that in addition to N-phenylpyrrolidine, N-methyl- and N-benzylpyrrolidine, as well as N-benzoylpyrrolidine, were arylated under the reaction conditions.

NMR Studies of Crowded Diels–Alder Adducts of 3,6‐Dibromophencyclone with N‐(2,6‐Dialkylphenyl)maleimides. Hindered Rotations and Magnetic Anisotropy. Ab Initio Calculations for Optimized Structures of the Precursor Maleimides and Their Adducts with Phencyclone and 3,6‐Dibromophencyclone

6,9‐Dibromo‐1,3‐diphenyl‐2H‐cyclopenta[l]phenanthren‐2‐one (commonly known as 3,6‐dibromophencyclone), 1b, reacted with N‐(2,6‐dimethylphenyl)maleimide, 2a; with N‐(2,6‐diethylphenyl)maleimide, 2b; and with N‐(2,6‐diisopropylphenyl)maleimide, 2c, respectively, to yield the corresponding Diels–Alder adducts, 4a–c. The adducts were extensively characterized by NMR (7 T) at ambient temperatures using one‐ and two‐dimensional (1D and 2D) proton and carbon‐13 techniques for assignments. Slow exchange limit (SEL) spectra were observed, demonstrating slow rotations on the NMR timescales, for the unsubstituted bridgehead phenyl groups [C(sp3)–C(aryl sp2) bond rotations] and for the 2,6‐dialkylphenyl groups [N(sp2)–C(aryl sp2) bond rotations]. Substantial magnetic anisotropic shifts were seen in the adducts. For example, in the N‐(2,6‐dialkylphenyl) moieties of the adducts, one of the alkyl groups is directed “into” the adduct cavity, toward the phenanthrenoid portion, and these “inner” alkyl proton NMR signals were shifted upfield. Thus, in CDCl3, the inner methyl of adduct 4a exhibits a proton resonance at −0.05 ppm, upfield of tetramethylsilane (TMS); the inner ethyl group signals from 4b appear at 0.09 ppm (CH2, quartet) and −0.11 ppm (CH3, triplet); and the inner isopropyl group from 4c is seen at −0.10 ppm (methine, approx. septet) and, −0.28 ppm (CH3, doublet). Ab initio molecular modeling results are presented for the precursor maleimides, 2, and their adducts, 3, from the parent phencyclone, 1a, at the restricted Hartree–Fock level using the 6‐31G* basis set. Results for the dibromoadducts, 4, used the LAV3P* basis set.

NMR Studies of Crowded Diels–Alder Adducts of Phencyclone with N‐(2,6‐Dialkylphenyl)maleimides. Hindered Rotations and Magnetic Anisotropy

Phencyclone, 1, reacted with N‐(2,6‐dimethylphenyl)maleimide, 2a; with N‐(2,6‐diethylphenyl)maleimide, 2b; and with N‐(2,6‐diisopropylphenyl)maleimide, 2c, respectively, to yield the corresponding Diels–Alder adducts, 3a–c. The adducts were extensively characterized by NMR (7 T) at ambient temperatures using one‐ and two‐dimensional (1D and 2D) proton and carbon‐13 techniques for assignments. Slow exchange limit (SEL) spectra were observed, demonstrating slow rotations on the NMR timescales, for the unsubstituted bridgehead phenyl groups [C(sp3)–C(aryl sp2) bond rotations] and for the 2,6‐dialkylphenyl groups [N(sp2)–C(aryl sp2) bond rotations]. Substantial magnetic anisotropic shifts were seen in the adducts. For example, in the N‐(2,6‐dialkylphenyl) moieties of the adducts, one of the alkyl groups is directed “into” the adduct cavity, toward the phenanthrenoid portion, and these “inner” alkyl proton NMR signals were shifted upfield. Thus, in CDCl3, the “inner” methyl of adduct 3a exhibits a proton resonance at −0.13 ppm, upfield of tetramethylsilane (TMS); the “inner” ethyl group signals from 3b appear at 0.026 ppm (CH2, quartet), and −0.21 ppm (CH3, triplet); and the “inner” isopropyl group from 3c is seen at −0.06 ppm (methine, approx. septet) and −0.39 ppm (CH3, doublet). Proton NMR of the crude N‐(2,6‐dialkylphenyl)maleamic acids (used as precursors of the maleimides, 2a–c) exhibited two sets of AB quartet signals, suggesting possible conformers from hindered rotation in the amide groups about the HN–C˭O bonds.

1H, 13C, and 19F NMR studies of phencyclone adducts of N-(polyhalophenyl)maleimides: evidence for dynamic NMR in maleamic acidsAb initio calculations for optimized structures

Abstract NMR methods, including one- and two-dimensional techniques (at 7.05 T) for 1H, 13C and 19F, have been applied to studies of hindered rotations and magnetic anisotropy in some crowded Diels–Alder adducts of phencyclone (1). Symmetrically substituted N-aryl maleimides (2) bearing numerous halogens on the N-aryl ring, were employed as dienophiles to form the target adducts (3). The maleimides included: N-(4-bromo-2,6-difluorophenyl)maleimide (2a); N-(2,3,5,6-tetrafluorophenyl)maleimide (2b); N-(4-bromo-2,3,5,6-tetrafluorophenyl)maleimide (2c); N-(2,3,4,5,6-pentachlorophenyl)maleimide (2d); and N-(2,4,6-tribromophenyl)maleimide (2e). Maleimides (2a–2c) were prepared from the precursor N-aryl maleamic acids (5a–5c). Ambient temperature fluorine-19 NMR of these maleamic acids in d6-acetone showed substantial unusual peak broadening consistent with intermediate exchange rate processes, which may correspond to the N-aryl rotation process. Maleimides (2d) and (2e) were produced in one step from pentachloroaniline or 2,4,6-tribromoaniline, respectively, and maleic anhydride with anhydrous ZnCl2 at ca. 200 °C. For the adducts (3), we observed slow exchange limit spectra on the 1H, 13C, [and 19F, for (3a–3c)] NMR timescales for the rotation of the unsubstituted bridgehead phenyls about the C(sp3) C(sp2) bonds, and for the rotations of the N-aryl rings about the N(sp2) C(aryl sp2) bonds. Ab initio calculations for geometry optimizations at the Hartree–Fock level with 6-31G* (or LACVP*) basis sets were performed for the adducts. We believe that this is the first report of detailed 1H, 13C, and 19F NMR data for a substantial collection of N-aryl maleamic acids, maleimides and their phencyclone adducts bearing multiple fluorines or other halogens directly on the N-aryl ring, together with complementary quantitative geometric parameters from high-level HF/6-31G* (or LACVP*) calculations.