Recent advances in radical-mediated fluorination through C–H and C–C bond cleavage

The C–H and C–C bonds are abundant in organic compounds, yet generally inert in chemical transformations. Therefore, direct functionalization of inert chemical bonds remains challenging. The fluorine-containing compounds are of special interest for their uses in medicinal chemistry. Direct fluorination of C–H and C–C bonds undoubtedly represents one of the most ideal and attractive approaches to incorporate fluorine atom into complex molecules. Herein, we summarize the recent advances in radical-mediated C–H and C–C bond fluorination. Three types of transformations are discussed: (1) direct C–H abstraction/fluorination of alkanes; (2) decarboxylative fluorination of alkyl carboxylic acids; (3) ring-opening fluorination.     

Cu(I) metal organic framework catalyzed C–C and C–N coupling reactions

DABCO (1,4-diazabicyclo[2.2.2]octane) based Cu(I) metal organic framework (here after represented as Cu(I)-MOF) catalyzed Sonogashira cross-coupling reaction of iodobenzene and phenylacetylene was conducted smoothly to afford diphenylacetylene in excellent yield under N₂ atmosphere. For comparative study, piperidine based Cu(I) clusters were also investigated. Among these catalysts, Cu(I)-MOF exhibited higher activity with good selectivity for the C–C cross-coupled product. Cu(I) catalysts investigated in this study exhibited similar activity in the C–C homo-coupling reaction of phenylacetylene in O₂ atmosphere. Application of these catalysts was extended in the C–N coupling reactions between phenylboronic acid and aromatic/aliphatic/heterocyclic amines. Cu(I)-MOF can be readily recovered from the reaction mixture and reused for several cycles without loss in the catalytic activity.     

Experimental study of Fe–C–O based system above 1,000 °C

The paper deals with the study of phase transformation temperatures of the model Fe–C–O based metallic alloys in the high temperature region (above 1,000 °C). Six model alloys with graded carbon and oxygen content were prepared and studied. Temperatures of phase transitions were obtained using DTA method (differential thermal analysis). The Setaram SETSYS 18? (TG/DTA/DSC/TMA) modular experimental system was used for measurements. Influence of composition change (carbon and oxygen content) on shift of phase transformation temperatures is investigated in this paper. New original data (phase transformation temperatures) were obtained in this study. Controlled heating of the alloys was conducted at the rates of 2, 4, 7, 10, 15 and 20 °C min^?1. Comparison of the obtained experimental data with the data presented in the literature was also carried out. It follows from comparison of the obtained results with the data accessible in the literature that a lack of experimental data exists, and these available data significantly differ.     

Experimental study of Fe–C–O based system below 1000 °C

The paper deals with the study of phase transformation temperatures of Fe (Fe–C–O) based metallic alloys. Six model alloys with graded carbon and oxygen content were used for experimental investigation. Low-temperature region (<1000 °C) was the investigated area. Phase transformation temperatures were obtained using Differential thermal analysis and Setaram Setsys 18_TM laboratory system. Controlled heating was conducted at the rates of 2, 4, 7, 10, 15, 20 °C min^?1. Region of eutectoid transformation (Fe_α(C) + Fe₃C → Fe_γ(C)), alpha–gamma (Fe_α(C) → Fe_γ(C)) and transformation Fe_α(O) + Fe_0.92O → Fe_γ(O) + Fe_0.92O was studied. New original data (phase transformation temperatures) were obtained in this study. The relationship between shift of phase transformation temperatures and chemical composition (mainly carbon and oxygen content) is investigated in this paper. To achieve good approximation to the equilibrium conditions, the extrapolation of the obtained phase transformation temperatures to the zero heating rate was performed. The influence of experimental conditions (heating rate) on temperatures of phase transformations was studied as well. Comparison of the obtained experimental data with the data presented in the accessible literature and IDS calculations (Solidification Analysis Package) was carried out. It follows from literature search that there is a lack of thermo-physical and thermo-dynamical data on Fe–C–O system.     

Stereoselective synthesis of C3–C17 and C18–C34 subunits of bullatanocin utilizing α-chloro sulfide intermediates

A convergent synthesis of bullatanocin is envisaged by the union of C18–C34, C3–C17 and the butenolide subunits. The synthesis of the C3–C17 and C18–C34 subunits is disclosed that takes advantage of the chirality of tartaric acid for 1,2-asymmetric induction, chloro sulfides for carbon chain elongation and [2,3] sigmatropic shift for the preparation of 1,4-diol moiety via efficient 1,3-chirality transfer. The THF ring is elaborated by intramolecular displacement.     

Stereoselective synthesis of C12–C21 common fragment of thermolides 1–5

A highly stereoselective synthesis of C12–C21 common fragment of thermolides 1–5 has been described. The salient features of the synthesis are the utilization of desymmetrization protocol, Barton-McCombie reaction, Brown’s asymmetric allylation and Wacker oxidation.     

C–H...O and C–H...N interactions in RNA structures

Small molecule studies indicate that C–H...X interactions (X: O,N) constitute weak H-bonds. We have performed a comprehensive analysis of their occurrence and geometry in RNA structures. Here, we report on statistical properties of the total set of interactions identified and discuss selected motifs. The distance/angle distribution of all interactions exhibits an excluded region where the allowed C–H...X angle range increases with an increasing H...X distance. The preferred short C–H...X interactions in RNA are backbone-backbone contacts between neighbour nucleotides. Distance/angle distributions generated for various interaction types can be used for error recognition and modelling. The axial C2′(H)...O4′ and C5′(H)...O2′ interactions connect two backbone segments and form a seven-membered ring that is specific for RNA. An AA base pair with one standard H-bond and one C–H...N interaction has been identified in various structures. Despite the occurrence of short C–H...X contacts their free energy contribution to RNA stability remains to be assessed. Received: 17 May 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998     

Transition metals catalyzed C–C and C–O bonds formation: facile synthesis of flavans and benzoxepines

A simple and practical method has been developed based on intermolecular [Pd]-catalyzed C–C and an intramolecular [Cu]-catalyzed C–O bond formations for the synthesis of flavans and benzoxepines. Interestingly, the method is amenable for the synthesis of a wide variety of flavans and benzoxepines with dense functionalities on aromatic moieties. Significantly, flavans and benzoxepines are present as core/part-structures in many biologically active natural products.     

Recent strategic advances for the activation of benzylic C–H bonds for the formation of C–C bonds

Alkylarenes, obtained from abundant hydrocarbon feedstock sources, are an attractive starting material for the formation of complex molecular architectures. Conventional activation strategies of the relatively inert sp³-hybridized benzylic C–H bonds usually require relatively harsh conditions and are difficult to apply to the synthesis of fine chemicals. The present review describes recent strategic advances for the activation of benzylic C–H bonds for the catalytic formation of C–C bonds. In particular, two activation methods, i.e., strategies that generate benzylic radicals or benzyl anions, are discussed.     

Liquid–liquid equilibria of alkane (C10–C14)+octylbenzene+sulfolane

The liquid–liquid equilibria (LLE) data are presented for mixtures of alkane (C10/C12/C14)+octylbenzene+sulfolane at 323.15, 348.15 and 373.15 K. The addition of octylbenzene to sulfolane is found to increase the solubility of alkanes in the order of decane>dodecane>tetradecane. The tie line data were correlated with the well-known UNIQUAC and NRTL models. The calculated values based on the UNIQUAC model were found to be better than those based on the NRTL model. The values of selectivity and distribution coefficient were derived from the equilibrium data.     

Discovery of redox system enabling C–N–C bonds formation: Unprecedented Aza-Cannizzaro reaction

A novel reaction involving in situ redox conversion of glyoxylate esters to glycine is described. Simple starting materials and mild conditions for the synthesis of glycine derivatives probably indicate a pathway towards prebiotic chemistry. This proceeds analogous to Cannizzaro reaction involving ammonia therefore it can be termed as intramolecular Aza-Cannizzaro type reaction. This reaction is examined in detail with an aid of computational analysis to corroborate the proposed mechanism.     

Carbon–hydrogen (C–H) bond activation at PdIV: a Frontier in C–H functionalization catalysis

The direct functionalization of carbon–hydrogen (C–H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C–H bond activation, catalytic processes that utilize a Pd^II/Pd^IV redox cycle are increasingly common. The C–H activation step in most of these catalytic cycles is thought to occur at a Pd^II centre. However, a number of recent reports have suggested the feasibility of C–H cleavage occurring at Pd^IV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at Pd^II. This mini review highlights proposed examples of C–H activation at Pd^IV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.     

C–C Bond Rupture in the Oxidation of Lower (C2–C6) Alcohols with Hydrogen Peroxide Mediated by Iron-Containing Compounds

C–C bond rupture upon the oxidation of alcohols in the Fe(ClO₄)₃+ H₂O₂system in aqueous acetonitrile at room temperature is found. The relative yield of the products of C–C bond rupture is 20–30% under standard conditions for C₂and C₃alcohols and decreases in the series C₂> C₃> C₄> C₆. The alkyl radical and carboxylic acid are the products of C–C bond rupture in alcohol oxidation. Cyclohexane is a competitive inhibiting agent for C–H bond oxidation in 1-propanol, and it does not affect the yield of the products of C–C bond rupture. When H₂O₂is replaced by tert-BuOOH, the fraction of the products of C–C bond rupture decreases by an order of magnitude. Our data suggest that a non-radical intermediate, likely Fe(III) hydroperoxo complex, is responsible for C–C bond rupture in alcohol under the reaction conditions.     

Base metal-catalyzed alcohol C–C couplings under hydrogen transfer conditions

Comparing to classical Grignard-type carbonyl additions, transfer hydrogenative C–C bond-forming reactions using alcohols as carbonyl precursors have shown remarkable advantages from the perspective of atom economy, step economy and redox economy. The significant drawbacks of conventional method, such as the use of multi-step reactions, the premetalated reagents, and stoichiometric oxidants and reductants, can be avoided by using hydrogen transfer processes. Moreover, the development of reactions employing earth-abundant and eco-friendly base metal as catalysts is an important objective in modern sustainable chemistry. In this review, we summarized recent advances in base metal-catalyzed C–C coupling of alcohols under hydrogen transfer conditions.     

Radical cascade reactions of unsaturated C–C bonds involving migration

During the past few years, with the rapid development of mild methods for the generation of radical species, great progress in radical cascade reactions of unsaturated C–C bonds has been made. Many radical cascade reactions involve functional groups migration, which leads structurally much more diverse, complex and valuable compounds not easily obtained through other methods. In this review, the recent achievements in unsaturated C–C bonds radical cascade reactions involving migration are summarized.     

Cobalt-catalyzed direct C–C bond formation between tetrahydrofuran and alkynes

We aimed to describe an efficient CoCl₂-catalyzed direct C–C bond formation of tetrahydrofuran (THF) with various alkynes in the presence of tert-butyl hydroperoxide and catalytic amount of acid to obtain vinyl-substituted THFs. Mono- and di-substituted alkynes were suitable for this transformation.     

Activation of propane C–H and C–C bonds by a diplatinum cluster: potential energy surfaces and reaction mechanisms

The activation mechanism of C₃H₈ catalyzed by the homonuclear bimetallic Pt₂ cluster has been detailedly explored on the singlet and triplet potential energy surfaces at BPW91/aug-cc-pvtz, Lanl2tz level. The C–H bond cleavage channel (dehydrogenation and the release of propylene) is kinetically predominant, whereas the C–C bond cleavage channel (demethanation and the release of ethane) should be ruled out. Furthermore, the release of propylene channel is kinetically favorable, while the dehydrogenation channel is thermodynamically preferable. Besides, both the C–H cleavage intermediate (Pt₂H₂C₃H₆b) and the C–C cleavage intermediates (CH₃HPt₂CHCH₃ and CH₃PtPtHC₂H₄) are thermodynamically preferred. The C–H cleavage intermediate (Pt₂H₂C₃H₆b) is kinetically favored, while the C–C cleavage intermediates (CH₃HPt₂CHCH₃ and CH₃PtPtHC₂H₄) are kinetically hindered. The homonuclear bimetallic Pt₂ cluster toward propane exhibits higher reactivity than the Pt atom, which is in good agreement with the experimental observation.     

An improved synthesis of the C42–C52 segment of ciguatoxin 3C

In our previously reported method for the construction of the IJKLM-ring of ciguatoxin 3C (CTX3C), the lengthy synthetic process for the intermediate C42–C52 (L-ring) segment was problematic. Therefore, a new and improved procedure for the C42–C52 segment, having modified protecting groups, was developed. The new route includes a chirality transferring Ireland-Claisen rearrangement for the construction of the vicinal dimethyl branching at C47–48, a one-pot cyclization process for the establishment of the stereocenters at C45 and C46 as well as the γ-hydroxy δ-lactone framework corresponding to the L-ring, and Brown’s asymmetric crotylboration for the installation of the stereocenters at C43 and C44. The new C42–C52 segment was successfully coupled with the previously reported C32–C41 (I-ring) segment to produce the IJKLM-ring.     

Hydrocarbons as proton donors in C–H⋯N and C–H⋯S hydrogen bonds

C–H?N and C–H?S hydrogen bonds were analyzed in complexes where acetylene, ethylene, methane and their derivatives are proton donors while ammonia and hydrogen sulfide are proton acceptors. Ab initio calculations were performed to analyze those interactions; MP2 method was applied and the following basis sets were used: 6-311++G(d,p), aug-cc-pVDZ and aug-cc-pVTZ. The results showed that hydrogen bonds for complexes with ammonia are systematically stronger than such interactions in complexes with hydrogen sulfide. If the fluorine substituted hydrocarbons are considered then F-substituents enhance the strength of hydrogen bonding. For a few complexes, mainly those where carbon atom in proton donating C–H bond possesses sp³ hybridization, the blue-shifting hydrogen bonds were detected. Additionally, Quantum Theory of ‘Atoms in Molecules’ and Natural Bond Orbitals method were applied to analyze H-bond interactions.