Lewis Acid–Base Interaction‐Controlled ortho‐Selective C−H Borylation of Aryl Sulfides

An iridium/bipyridine‐catalyzed ortho ‐selective C−H borylation of aryl sulfides was developed. High ortho ‐selectivity was achieved by a Lewis acid–base interaction between a boryl group of the ligand and a sulfur atom of the substrate. This is the first example of a catalytic and regioselective C−H transformation controlled by a Lewis acid–base interaction between a ligand and a substrate. The C−H borylation reaction could be conducted on a gram scale, and with a bioactive molecule as a substrate, demonstrating its applicability to late‐stage regioselective C−H borylation. A bioactive molecule was synthesized from an ortho ‐borylated product by converting the boryl and methylthio groups of the product.     

Ligand‐Enabled Auxiliary‐Free meta‐C−H Arylation of Phenylacetic Acids

The meta ‐C−H arylation of free phenylacetic acid was realized using 2‐carbomethoxynorbornene (NBE‐CO₂Me) as a transient mediator. Both the modified norbornene and the mono‐protected 3‐amino‐2‐hydroxypyridine type ligand are crucial for this auxiliary‐free meta ‐C−H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta ‐arylated products in high yields.     

Ruthenium‐Catalyzed para‐Selective C−H Alkylation of Aniline Derivatives

The para ‐selective C−H alkylation of aniline derivatives furnished with a pyrimidine auxiliary is herein reported. This reaction is proposed to take place via an N−H‐activated cyclometalate formed in situ. Experimental and DFT mechanistic studies elucidate a dual role of the ruthenium catalyst. Here the ruthenium catalyst can undergo cyclometalation by N−H metalation (as opposed to C−H metalation in meta ‐selective processes) and form a redox active ruthenium species, to enable site‐selective radical addition at the para position.     

4‐Amino‐7‐(2‐de­oxy‐2‐fluoro‐β‐d‐arabinofuranos­yl)‐5‐fluoro‐7H‐pyrrolo[2,3‐d]pyrimidine: a bis‐fluorinated analogue of 2′‐deoxy­tubercidin

The title compound, C₁₁H₁₂F₂N₄O₃, exhibits an anti glycosylic bond conformation, with a torsion angle χ = −117.8 (2)°. The sugar pucker is N‐type (C4′‐exo, between ³T₄ and E₄, with P = 45.3° and τ_m = 41.3°). The conformation around the exocyclic C—C bond is −ap (trans), with a torsion angle γ = −177.46 (15)°. The nucleobases are stacked head‐to‐head. The crystal structure is characterized by a three‐dimensional hydrogen‐bond network involving N—H⋯O, O—H⋯O and O—H⋯N hydrogen bonds.     

Ruthenium(II)‐Catalyzed meta C−H Mono‐ and Difluoromethylations by Phosphine/Carboxylate Cooperation

Ruthenium(II)‐catalyzed meta ‐selective C−H (di)fluoromethylation was accomplished by phosphine and carboxylate cooperation. The remote C−H functionalization was characterized by ample substrate scope, thereby setting the stage for meta ‐(di)fluoromethylation through facile C−H cleavage.     

Intra‐ and Intermolecular H‐Bonds of Alcohols in DMSO, 1H‐NMR Analysis of Inter‐Residue H‐Bonds in Selected Oligosaccharides: Cellobiose,Lactose, N,N′‐Diacetylchitobiose,Maltose, Sucrose,Agarose, and Hyaluronates

Inter‐residue H‐bonds of oligosaccharides in (D₆)DMSO have been assigned on the basis of a combined interpretation of the chemical shift (δ(OH)), coupling constant (J(H,OH)), and temperature dependence (Δδ(OH)/ΔT) of OH signals. Cellobiose, lactose, and N,N′‐diacetylchitobiose possess a completely persistent C(3)OH⋅⋅⋅OC(5′) H‐bond. Maltose is characterised by flip‐flop H‐bonds between HO−C(3) and HO−C(2′), and agarose by two weakly persistent inter‐residue H‐bonds. Sucrose forms an equilibrium of differently H‐bonded species, and hyaluronates possess four strong inter‐residue H‐bonds.     

2′‐De­oxy‐2‐fluoro­tubercidin

In the title compound [systematic name: 7‐(2‐de­oxy‐β‐d ‐erythro‐pentofuranos­yl)‐2‐fluoro‐7H‐pyrrolo[2,3‐d]pyrimidin‐2‐amine], C₁₁H₁₃FN₄O₃, the conformation of the N‐glycosylic bond is between anti and high‐anti [χ = −110.2 (3)°]. The 2′‐deoxy­ribofuranosyl unit adopts the N‐type sugar pucker (₄T³), with P = 40.3° and τ_m = 39.2°. The orientation of the exocyclic C4′—C5′ bond is −ap (trans), with a torsion angle γ = −168.39 (18)°. The nucleobases are arranged head‐to‐head. The crystal structure is stabilized by four inter­molecular hydrogen bonds of types N—H⋯N, N—H⋯O and O—H⋯O.     

Practical Alkoxythiocarbonyl Auxiliaries for Iridium(I)‐Catalyzed C−H Alkylation of Azacycles

The development of new and practical 3‐pentoxythiocarbonyl auxiliaries for Ir^I‐catalyzed C−H alkylation of azacycles is described. This method allows for the α‐C−H alkylation of a variety of substituted pyrrolidines, piperidines, and tetrahydroisoquinolines through alkylation with alkenes. While the practicality of these simple carbamate‐type auxiliaries is underscored by the ease of installation and removal, the method's utility is demonstrated in its ability to functionalize biologically relevant l ‐proline and l ‐trans ‐hydroxyproline, delivering unique 2,5‐dialkylated amino acid analogues that are not accessible by other C−H functionalization methods.     

1H‐NMR Analysis of Intra‐ and Intermolecular H‐Bonds of Alcohols in DMSO: Chemical Shift of Hydroxy Groups and Aspects of Conformational Analysis of Selected Monosaccharides,Inositols, and Ginkgolides

The interpretation of ¹H‐NMR chemical shifts, coupling constants, and coefficients of temperature dependence (δ(OH), J(H,OH), and Δδ(OH)/ΔT values) evidences that, in (D₆)DMSO solution, the signal of an OH group involved as donor in an intramolecular H‐bond to a hydroxy or alkoxy group is shifted upfield, whereas the signal of an OH group acting as acceptor of an intramolecular H‐bond and as donor in an intermolecular H‐bond to (D₆)DMSO is shifted downfield. The relative strength of the intramolecular H‐bond depends on co‐operativity and on the acidity of OH groups. The acidity of OH groups is enhanced when they are in an antiparallel orientation to a C−O bond. A comparison of the ¹H‐NMR spectra of alcohols in CDCl₃ and (D₆)DMSO allows discrimination between weak and strong intramolecular H‐bonds. Consideration of IR spectra (CHCl₃ or CH₂Cl₂) shows that the rule according to which the downfield shift of δ(OH) for H‐bonded alcohols in CDCl₃ parallels the strength of the H‐bond is valid only for alcohols forming strong intramolecular H‐bonds. The combined analysis of J(H,OH) and δ(OH) values is illustrated by the interpretation of the spectra of the epoxyalcohols 14 and 15 (Fig. 3). H‐Bonding of hexopyranoses, hexulopyranoses, alkyl hexopyranosides, alkyl 4,6‐O‐benzylidenehexopyranosides, levoglucosans, and inositols in (D₆)DMSO was investigated. Fully solvated non‐anomeric equatorial OH groups lacking a vicinal axial OR group (R=H or alkyl, or (alkoxy)alkyl) show characteristic J(H,OH) values of 4.5 – 5.5 Hz and fully solvated non‐anomeric axial OH groups lacking an axial OR group in β‐position are characterized by J(H,OH) values of 4.2 – 4.4 Hz (Figs. 4 – 6). Non‐anomeric equatorial OH groups vicinal to an axial OR group are involved in a partial intramolecular H‐bond (J(H,OH)=5.4 – 7.4 Hz), whereas non‐anomeric equatorial OH groups vicinal to two axial OR form partial bifurcated H‐bonds (J(H,OH)=5.8 – 9.5 Hz). Non‐anomeric axial OH groups form partial intramolecular H‐bonds to a cis‐1.3‐diaxial alkoxy group (as in 29 and 41 : J(H,OH)=4.8 – 5.0 Hz). The persistence of such a H‐bond is enhanced when there is an additional H‐bond acceptor, such as the ring O‐atom ( 43 – 47 : J(H,OH)=5.6 – 7.6 Hz; 32 and 33 : 10.5 – 11.3 Hz). The (partial) intramolecular H‐bonds lead to an upfield shift (relative to the signal of a fully solvated OH in a similar surrounding) for the signal of the H‐donor. The shift may also be related to the signal of the fully solvated, equatorial HO−C(2), HO−C(3), and HO−C(4) of β‐D ‐glucopyranose ( 16 : 4.81 ppm) by using the following increments: −0.3 ppm for an axial OH group, 0.2 – 0.25 ppm for replacing a vicinal OH by an OR group, ca. 0.1 ppm for replacing another OH by an OR group, 0.2 ppm for an antiperiplanar C−O bond, −0.3 ppm if a vicinal OH group is (partially) H‐bonded to another OR group, and −0.4 to −0.6 for both OH groups of a vicinal diol moiety involved in (partial) divergent H‐bonds. Flip‐flop H‐bonds are observed between the diaxial HO−C(2) and HO−C(4) of the inositol 40 (J(H,OH)=6.4 Hz, δ(OH)=5.45 ppm) and levoglucosan ( 42 ; J(H,OH)=6.7 – 7.1 Hz, δ(OH)=4.76 – 4.83 ppm; bifurcated H‐bond); the former is completely persistent and the latter to ca. 40%. A persistent, unidirectional H‐bond C(1)−OH⋅⋅⋅O−C(10) is present in ginkgolide B and C, as evidenced by strongly different δ(OH) and Δδ(OH)/ΔT values for HO−C(1) and HO−C(10) (Fig. 9). In the absence of this H‐bond, HO−C(1) of 52 resonates 1.1 – 1.2 ppm downfield, while HO−C(10) of ginkgolide A and of 48 – 50 resonates 0.5 – 0.9 ppm upfield.     

para‐Selective C−H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis

para ‐Selective C−H borylation of benzamides and pyridines has been achieved by cooperative iridium/aluminum catalysis. A combination of iridium catalysts commonly employed for arene C−H borylation and bulky aluminum‐based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C−H borylation to give variously substituted (hetero)arylboronates, which are versatile synthetic intermediates for complex multi‐substituted aromatic compounds.     

Iridium‐Catalyzed,Silyl‐Directed,peri‐Borylation of C−H Bonds in Fused Polycyclic Arenes and Heteroarenes

peri‐Disubstituted naphthalenes exhibit interesting physical properties and unique chemical reactivity, due to the parallel arrangement of the bonds to the two peri‐disposed substituents. Regioselective installation of a functional group at the position peri to 1‐substituted naphthalenes is challenging due to the steric interaction between the existing substituent and the position at which the second one would be installed. We report an iridium‐catalyzed borylation of the C−H bond peri to a silyl group in naphthalenes and analogous polyaromatic hydrocarbons. The reaction occurs under mild conditions with wide functional group tolerance. The silyl group and the boryl group in the resulting products are precursors to a range of functional groups bound to the naphthalene ring through C−C, C−O, C−N, C−Br and C−Cl bonds.     

Hydroarylation of 2‐Aryloxybut‐1‐en‐3‐ynes via Pd/Acid‐Catalyzed C−H Bond Activation: A Concise Synthesis of 2,3‐Bismethylene‐2,3‐dihydrobenzofurans

An intramolecular exo ‐hydroarylation of 2‐aryloxy‐1,4‐disilylbut‐1‐en‐3‐ynes via ortho ‐C−H bond activation under palladium(0) and acid catalysis was found to give 2,3‐bis(silylmethylidene)‐2,3‐dihydrobenzofurans. The two silyl groups present probably promoted the reaction and played a key role in stabilizing the diene moiety in the product. The products readily led to functionalized condensed cycles by a Diels–Alder reaction.     

2‐Amino‐8‐(2‐deoxy‐2‐fluoro‐β‐d‐arabinofuranosyl)imidazo[1,2‐a][1,3,5]triazin‐4(8H)‐one monohydrate,a 2′‐deoxyguanosine analogue with an altered Watson–Crick recognition site

The title compound, C₁₀H₁₂FN₅O₄·H₂O, shows an anti glycosyl orientation [χ = −123.1 (2)°]. The 2‐deoxy‐2‐fluoroarabinofuranosyl moiety exhibits a major C2′‐endo sugar puckering (S‐type, C2′‐endo–C1′‐exo, ²T₁), with P = 156.9 (2)° and τ_m = 36.8 (1)°, while in solution a predominantly N conformation of the sugar moiety is observed. The conformation around the exocyclic C4′—C5′ bond is −sc (trans, gauche), with γ = −78.3 (2)°. Both nucleoside and solvent molecules participate in the formation of a three‐dimensional hydrogen‐bonding pattern via intermolecular N—H...O and O—H...O hydrogen bonds; the N atoms of the heterocyclic moiety and the F substituent do not take part in hydrogen bonding.     

Transition‐metal‐free Chemoselective Oxidative C−C Coupling of the sp3 C−H Bond of Oxindoles with Arenes and Addition to Alkene: Synthesis of 3‐Aryl Oxindoles,and Benzofuro‐ and Indoloindoles

A transition‐metal (TM)‐free and halogen‐free NaOt Bu‐mediated oxidative cross‐coupling between the sp³ C−H bond of oxindoles and sp² C−H bond of nitroarenes has been developed to access 3‐aryl substituted and 3,3‐aryldisubstituted oxindoles in DMSO at room temperature in a short time. Interestingly, the sp³ C−H bond of oxindoles could also react with styrene under TM‐free conditions for the practical synthesis of quaternary 3,3‐disubstituted oxindoles. The synthesized 3‐oxindoles have also been further transformed into advanced heterocycles, that is, benzofuroindoles, indoloindoles, and substituted indoles. Mechanistic experiments of the reaction suggests the formation of an anion intermediate from the sp³ C−H bond of oxindole by tert ‐butoxide base in DMSO. The addition of nitrobenzene to the in‐situ generated carbanion leads to the 3‐(nitrophenyl)oxindolyl carbanion in DMSO which is subsequently oxidized to 3‐(nitro‐aryl) oxindole by DMSO.     

Selective Palladium(II)‐Catalyzed Carbonylation of Methylene β‐C−H Bonds in Aliphatic Amines

Palladium(II)‐catalyzed C−H carbonylation reactions of methylene C−H bonds in secondary aliphatic amines lead to the formation of trans ‐disubstituted β‐lactams in excellent yields and selectivities. The generality of the C−H carbonylation process is aided by the action of xantphos‐based ligands and is important in securing good yields for the β‐lactam products.     

Ligand‐Promoted Rhodium(III)‐Catalyzed ortho‐C−H Amination with Free Amines

Ligand development for rhodium(III)‐catalyzed C−H activation reactions has largely been limited to cyclopentadienyl (Cp) based scaffolds. 2‐Methylquinoline has now been identified as a feasible ligand that can coordinate to the metal center of Cp*RhCl to accelerate the cleavage of the C−H bond of N ‐pentafluorophenylbenzamides, providing a new structural lead for ligand design. The compatibility of this reaction with secondary free amines and anilines also overcomes the limitations of palladium(II)‐catalyzed C−H amination reactions.     

2′‐Deoxy‐7‐propynyl‐7‐deaza­adenosine: a DNA duplex‐stabilizing nucleoside

In the title compound, 2′‐deoxy‐7‐propynyl‐7‐deaza­adenosine, C₁₄H₁₆N₄O₃, the torsion angle of the N‐glycosylic bond is anti [χ = −130.7 (2)°]. The sugar pucker of the 2′‐deoxy­ribo­furanosyl moiety is C2′‐endo–C3′‐exo, ²T₃ (S‐type), with P = 185.9 (2)° and τ_m = 39.1 (1)°, and the orientation of the exocyclic C4′—C5′ bond is −ap (trans). The 7‐substituted propynyl group is nearly coplanar with the heterocyclic base moiety. Mol­ecules of the nucleoside form a layered network in which the heterocyclic bases are stacked head‐to‐tail with a closest distance of 3.197 (1) Å. The crystal structure of the nucleoside is stabilized by three inter­molecular hydrogen bonds of types N—H⋯ O, O—H⋯ N and O—H⋯ O.     

2,2′‐Anhydro‐1‐(3′,5′‐di‐O‐acetyl‐β‐D‐arabinofuranosyl)uracil,a cyclouridine nucleoside with a C4′‐endo furanosyl conformation

2,2′‐Anhydro‐1‐(3′,5′‐di‐O‐acetyl‐β‐D‐arabinofuranosyl)uracil, C₁₃H₁₄N₂O₇, was obtained by refluxing 2′,3′‐O‐(methoxymethylene)uridine in acetic anhydride. The structure exhibits a nearly perfect C4′‐endo (⁴E) conformation. The best four‐atom plane of the five‐membered furanose ring is O—C—C—C, involving the C atoms of the fused five‐membered oxazolidine ring, and the torsion angle is only −0.4 (2)°. The oxazolidine ring is essentially coplanar with the six‐membered uracil ring [r.m.s. deviation = 0.012 (5) Å and dihedral angle = −3.2 (3)°]. The conformation at the exocyclic C—C bond is gauche–trans which is stabilized by various C—H...π and C—O...π interactions.     

Synthesis of Substituted 2‐Amino‐1,3‐oxazoles via Copper‐Catalyzed Oxidative Cyclization of Enamines and N,N‐Dialkyl Formamides

A facile synthesis of 2‐amino‐1,3‐oxazoles via Cu^I‐catalyzed oxidative cyclization of enamines and N ,N ‐dialkyl formamides has been developed. The reaction proceeds through an oxidative C−N bond formation, followed by an intramolecular C(sp²)−H bond functionalization/C−O cyclization in one pot. This protocol provides direct access to useful 2‐amino‐1,3‐oxazoles and features protecting‐group‐free nitrogen sources, readily available starting materials, a broad substrate scope and mild reaction conditions.     

A low‐temperature modification of hexa‐tert‐butyldisilane and a new polymorph of 1,1,2,2‐tetra‐tert‐butyl‐1,2‐diphenyldisilane

Crystals of hexa‐tert‐butyldisilane, C₂₄H₅₄Si₂, undergo a reversible phase transition at 179 (2) K. The space group changes from Ibca (high temperature) to Pbca (low temperature), but the lattice constants a, b and c do not change significantly during the phase transition. The crystallographic twofold axis of the molecule in the high‐temperature phase is replaced by a noncrystallographic twofold axis in the low‐temperature phase. The angle between the two axes is 2.36 (4)°. The centre of the molecule undergoes a translation of 0.123 (1) Å during the phase transition, but the conformation angles of the molecule remain unchanged. Between the two tri‐tert‐butylsilyl subunits there are six short repulsive intramolecular C—H...H—C contacts, with H...H distances between 2.02 and 2.04 Å, resulting in a significant lengthening of the Si—Si and Si—C bonds. The Si—Si bond length is 2.6863 (5) Å and the Si—C bond lengths are between 1.9860 (14) and 1.9933 (14) Å. Torsion angles about the Si—Si and Si—C bonds deviate by approximately 15° from the values expected for staggered conformations due to intramolecular steric H...H repulsions. A new polymorph is reported for the crystal structure of 1,1,2,2‐tetra‐tert‐butyl‐1,2‐diphenyldisilane, C₂₈H₄₆Si₂. It has two independent molecules with rather similar conformations. The Si—Si bond lengths are 2.4869 (8) and 2.4944 (8) Å. The C—Si—Si—C torsion angles deviate by between −3.4 (1) and −18.5 (1)° from the values expected for a staggered conformation. These deviations result from steric interactions. Four Si—C(t‐Bu) bonds are almost staggered, while the other four Si—C(t‐Bu) bonds are intermediate between a staggered and an eclipsed conformation. The latter Si—C(t‐Bu) bonds are about 0.019 (2) Å longer than the staggered Si—C(t‐Bu) bonds.