Alkanes Research Articles

Decarboxylative Radical Sulfilimination via Photoredox, Copper, and Brønsted Base Catalysis

AbstractSulfilimines, the aza‐variants of sulfoxides, are key structural motifs in natural products, pharmaceuticals, and agrochemicals; and sulfilimine synthesis is therefore important in organic chemistry. However, methods for radical sulfilimination remain elusive, and as a result, the structural diversity of currently available sulfilimines is limited. Herein, we report the first protocol for decarboxylative radical sulfilimination reactions between sulfenamides and N‐hydroxyphthalimide esters of primary, secondary, and tertiary alkyl carboxylic acids, which were achieved via a combination of photoredox, copper, and Brønsted base catalysis. This novel protocol provided a wide variety of sulfilimines, in addition to serving as an efficient route for the synthesis of S‐alkyl/S‐aryl homocysteine sulfilimines and S‐(4‐methylphenyl) homocysteine sulfoximine. Moreover, it could be used for late‐stage introduction of a sulfilimine group into structurally complex molecules, thereby avoiding the need to preserve labile organosulfur moieties through multistep synthetic sequences. A mechanism involving photocatalytic substrate transformation and copper‐mediated C(sp3)−S bond formation is proposed.

Kinetically-Controlled Ni-Catalyzed Direct Carboxylation of Unactivated Secondary Alkyl Bromides without Chain Walking.

Herein, we report the direct carboxylation of unactivated secondary alkyl bromides enabled by the merger of photoredox and nickel catalysis, a previously inaccessible endeavor in the carboxylation arena. Site-selectivity is dictated by a kinetically controlled insertion of CO2 at the initial C(sp3)-Br site by the rapid formation of Ni(I)-alkyl species, thus avoiding undesired β-hydride elimination and chain-walking processes. Preliminary mechanistic experiments reveal the subtleties of stereoelectronic effects for guiding the reactivity and site-selectivity.

Decarboxylative Radical Sulfilimination via Photoredox, Copper, and Brønsted Base Catalysis.

Sulfilimines, the aza-variants of sulfoxides, are key structural motifs in natural products, pharmaceuticals, and agrochemicals; and sulfilimine synthesis is therefore important in organic chemistry. However, methods for radical sulfilimination remain elusive, and as a result, the structural diversity of currently available sulfilimines is limited. Herein, we report the first protocol for decarboxylative radical sulfilimination reactions between sulfenamides and N-hydroxyphthalimide esters of primary, secondary, and tertiary alkyl carboxylic acids, which were achieved via a combination of photoredox, copper, and Brønsted base catalysis. This novel protocol provided a wide variety of sulfilimines, in addition to serving as an efficient route for the synthesis of S-alkyl/S-aryl homocysteine sulfilimines and S-(4-methylphenyl) homocysteine sulfoximine. Moreover, it could be used for late-stage introduction of a sulfilimine group into structurally complex molecules, thereby avoiding the need to preserve labile organosulfur moieties through multistep synthetic sequences. A mechanism involving photocatalytic substrate transformation and copper-mediated C(sp3 )-S bond formation is proposed.

Psychedelic-like Activity of Norpsilocin Analogues.

Primary metabolites of mushroom tryptamines, psilocybin and baeocystin (i.e., psilocin and norpsilocin), exhibit potent agonist activity at the serotonin 2A receptor (5-HT2A) in vitro but differ in their 5-HT2A-mediated effects in vivo. In particular, psilocin produces centrally mediated psychedelic effects in vivo, whereas norpsilocin, differing only by the loss of an N-methyl group, is devoid of psychedelic-like effects. These observations suggest that the secondary methylamine group in norpsilocin impacts its central nervous system (CNS) bioavailability but not its receptor pharmacodynamics. To test this hypothesis, eight norpsilocin derivatives were synthesized with varied secondary alkyl-, allyl-, and benzylamine groups, primarily aiming to increase their lipophilicity and brain permeability. Structure-activity relationships for the norpsilocin analogues were evaluated using the mouse head-twitch response (HTR) as a proxy for CNS-mediated psychedelic-like effects. HTR studies revealed that extending the N-methyl group of norpsilocin by a single methyl group, to give the corresponding secondary N-ethyl analogue (4-HO-NET), was sufficient to produce psilocin-like activity (median effective dose or ED50 = 1.4 mg/kg). Notably, N-allyl, N-propyl, N-isopropyl, and N-benzyl derivatives also induced psilocin-like HTR activity (ED50 = 1.1-3.2 mg/kg), with variable maximum effects (26-77 total HTR events). By contrast, adding bulkier tert-butyl or cyclohexyl groups in the same position did not elicit psilocin-like HTRs. Pharmacological assessments of the tryptamine series in vitro demonstrated interactions with multiple serotonin receptor subtypes, including 5-HT2A, and other CNS signaling proteins (e.g., sigma receptors). Overall, our data highlight key structural requirements for CNS-mediated psychedelic-like effects of norpsilocin analogues.

Organocatalytic Asymmetric Synthesis of Si-Stereogenic Siloxanols.

We report the organocatalytic synthesis of Si-stereogenic compounds via desymmetrization of a prochiral silanediol with a chiral imidazole-containing catalyst. This metal-free silylation method affords high yields with enantioselectivity up to 98:2 for various silanediol and silyl chloride substrate combinations (including secondary alkyl, vinyl, and H groups), accessing products with potential for further elaboration. NMR and X-ray studies reveal insight into the H-bonding interactions between the imidazole organocatalyst and the silanediol and the dual activating role of the Lewis basic imidazole to account for the high enantioselectivity.

Synthesis and properties of secondary alkyl sulfonates

Currently, there are totaling two production methods of sodium secondary alkyl sulfonate SAS 60, that are, sulfochlorination and sulfoxidation. These two methods involving SO2 (the first one is also Cl2) may be harmful to the enviroment. In this paper, sodium secondary alkyl sulfonate was synthesized by NaHSO3 addition reaction of dodecane’s double bond with azodiisobutyronitrile as catalyst, and the yield was over 95% within 2 h. The reaction avoids SO2 and Cl2, with the preparation process being simple and safe. The target product β-sodium dodecyl sulfonate was characterized by FT-IR, mass spectrometry,1H NMR and 13C NMR characterization. The physical and chemical properties such as surface tension, contact angle, wettability, emulsification, foaming and decontamination were tested. The results demonstrate that the Krafft point for the determination of sodium secondary alkyl sulfonate is 26 °C, with its CMC of 2.93 × 10−3 mol/L and γcmc of 27.06 mN/m according to γ-lgc curve. The results of thermodynamic parameters depict that micellization of the surfactants is a spontaneous process. Compared with conventional SAS 60, sodium secondary alkyl sulfonate is an anionic surfactant with excellent emulsifying ability, favorable foam performance and corking foam stability.

Photoexcitation of (diarylmethylene)amino benziodoxolones for alkylamination of styrene derivatives with carboxylic acids.

The alkylamination of alkenes using pristine carboxylic acids was achieved by the photoexcitation of (diarylmethylene)amino benziodoxolones (DABXs), which serve as both an oxidant and an aminating reagent (an iminyl radical precursor). The developed method is a simple photochemical reaction without the need for external photosensitizers and shows a broad substrate scope for aliphatic carboxylic acids leading to the formation of primary, secondary, and tertiary alkyl radicals, thus enabling the facile synthesis of various structurally complex amines. Mechanistic investigations including transient absorption spectroscopy measurements using a laser flash photolysis (LFP) method disclosed the unique photochemical reactivity of DABXs, which undergoes homolysis of their I-N bonds to give an iminyl radical and ortho-iodobenzoyloxy radical, the latter of which participates in the single-electron oxidation of carboxylates.

Catalytic tert-alkylation of enamides via C-C bond cleavage under photoredox conditions.

Efficient C-C bond cleavage is recognized as a persistent challenge in the field of synthetic methodology. In this study, we found that tertiary alkyl radicals are smoothly formed from tertiary alkylated dienones (BHT adducts) via SET, using PDI as a photocatalyst. Resulting tert-alkyl radicals could be applied to the tert-alkylation of enamides. The driving force of this C-C bond cleavage reaction is the mesolytic cleavage of the BHT adducts. The mechanistic study revealed that PDI anion radical is the key active species during the catalytic cycle.

Regioselective synthesis of N-containing polycyclic compounds via radical annulation cyclization of 1,7-dienes with aldehydes.

A convenient method for oxidant-promoted radical cascade acylation or decarbonylative alkylation of 1,7-dienes with aldehydes has been established. This method allows for the rapid construction of N-containing polycyclic skeletons in a highly regio- and stereoselective manner. This transformation provides a simple and efficient method for the preparation of a range of tetrahydro-6H-indeno[2,1-c]quinolinone derivatives by sequential formation of three new carbon-carbon bonds. Additionally, this radical cascade cyclization can selectively convert aldehydes into aroyl/primary aliphatic acyl radicals and secondary or tertiary alkyl radicals.

Metal- and light-free decarboxylative direct C-H alkylation of heteroarenes at room temperature.

This study reports a metal- and light-free decarboxylative C-H alkylation of heteroarenes at room temperature. The reaction generates various primary, secondary, and tertiary alkyl radicals and functionalizes seven different privileged scaffolds widely present in bioactive molecules. During this process, one equivalent of hypervalent iodine(III) carboxylates (HICs) plays dual roles as an alkyl radical precursor and an oxidant.

Photoredox-catalyzed radical-radical cross coupling of ketyl radicals with unstabilized primary alkyl radicals.

Herein, a novel protocol dealing with the preparation of sterically hindered alcohols has been successfully developed via radical-radical coupling reactions enabled by mild and redox-neutral photocatalysis. With alkylsilicates as the radical precursors, a range of primary alkyl radicals bearing various functional groups could couple with a range of phthalimides and activated ketones.

Iodine-promoted transfer of dihydrogen from ketones to alkenes, triphenylmethyl, and diphenylmethyl derivatives.

Herein, a novel class of transfer hydrogenation agent, cycloheptanone, was successfully employed in metal-free hydrogenation facilitated by iodine. A series of alkenes, triphenylmethyl derivatives, and diphenylmethyl derivatives were reduced to the desired compounds in moderate to excellent yields. The transfer hydrodeuteration of alkenes using α-deuterated cyclododecanone exhibited high regioselectivity. Preliminary mechanism studies confirmed the origins of the two hydrogen atoms involved in the reduction of alkenes. The current study paves the way for the use of ketones as unique transfer hydrogenation agents in chemical synthesis.

Discrimination of Diptera order insects based on their saturated cuticular hydrocarbon content using a new microextraction procedure and chromatographic analysis.

The nature and proportions of hydrocarbons in the cuticle of insects are characteristic of the species and age. Chemical analysis of cuticular hydrocarbons allows species discrimination, which is of great interest in the forensic field, where insects play a crucial role in estimating the minimum post-mortem interval. The objective of this work was the differentiation of Diptera order insects through their saturated cuticular hydrocarbon compositions (SCHCs). For this, specimens fixed in 70 : 30 ethanol : water, as recommended by the European Association for Forensic Entomology, were submitted to solid-liquid extraction followed by dispersive liquid-liquid microextraction, providing preconcentration factors up to 76 for the SCHCs. The final organic extract was analysed by gas chromatography coupled with flame ionization detection (GC-FID), and GC coupled with mass spectrometry was applied to confirm the identity of the SCHCs. The analysed samples contained linear alkanes with the number of carbon atoms in the C9-C15 and C18-C36 ranges with concentrations between 0.1 and 125 ng g-1. Chrysomya albiceps (in its larval stage) showed the highest number of analytes detected, with 21 compounds, while Lucilia sericata and Calliphora vicina the lowest, with only 3 alkanes. Non-supervised principal component analysis and supervised orthogonal partial least squares discriminant analysis were performed and an optimal model to differentiate specimens according to their species was obtained. In addition, statistically significant differences were observed in the concentrations of certain SCHCs within the same species depending on the stage of development or the growth pattern of the insect.

Elucidating metal composition–coking relationships and coke formation pathways during gas-phase oxydehydration of glycerol over clay mineral-supported Mo-V-O catalysts

Catalyst deactivation by carbon deposition (coking) remains a major obstacle in many important industrial processes, such as catalytic gas-phase oxydehydration of glycerol. Understanding the chemical nature and development of coke species during the time-on-stream (TOS) of the catalytic solids is therefore crucial for mitigating the extent of coking and in the design of regeneration process of the coked catalysts. In this study, multiple analytical techniques, including SEM, XRD, FTIR, Raman, GC-MS, XPS, and 13C solid-state MAS NMR were employed to gain insights into the coking behavior of acid-activated montmorillonite (HMMT) supported Mo-V-O catalysts with modulated metal ratios, along with soluble and insoluble coke compositions and their evolution over time. Insoluble coke was comprised of polycyclic aromatic compounds with 5 or more fused-benzene rings containing different types of oxygen-bonded groups, such as −OCH3, −COOH, −CHO, and −OH. The major chemical constituents of soluble coke were mononuclear aromatic derivatives (i.e., xylenes, 2,4-di-tert-butylphenol, and 1-hydroxycyclohexyl phenyl ketone) and paraffinic hydrocarbons with 12–18 carbon atoms. The latter coke species is thought to be formed via the deoxygenation of linear oligoglycerols. The insights presented in this study may aid in understanding the carbon deposition process during gas-phase oxydehydration of glycerol for improved design of supported Mo-V-O catalyst materials with high coking resistance.

Electron-induced hydroamination of ethane as compared to ethene: implications for the reaction mechanism.

The properties of carbonaceous materials with respect to various applications are enhanced by incorporation of nitrogen-containing moieties like, for instance, amino groups. Therefore, processes that allow the introduction of such functional groups into hydrocarbon compounds are of utmost interest. Previous studies have demonstrated that hydroamination reactions which couple amines to unsaturated sites within hydrocarbon molecules do not only proceed in the presence of suitably tailored catalysts but can also be induced and controlled by electron irradiation. However, studies on electron-induced hydroaminations so far were guided by the hypothesis that unsaturated hydrocarbons are required for the reaction while the reaction would be much less efficient in the case of saturated hydrocarbons. The present work evaluates the validity of this hypothesis by post-irradiation thermal desorption experiments that monitor the electron energy-dependent yield of ethylamine after electron irradiation of mixed C2H4:NH3 and C2H6:NH3 ices with the same composition and thickness. The results reveal that, in contrast to the initial assumption, ethylamine is formed with similar efficiency in both mixed ices. From the dependence of the product yields on the electron energy, we conclude that the reaction in both cases is predominantly driven by electron ionization of NH3. Ethylamine is formed via alternative reaction mechanisms by which the resulting NH2˙ radicals add to C2H4 and C2H6, respectively. The similar efficiency of amine formation in unsaturated and saturated hydrocarbons demonstrates that electron irradiation in the presence of NH3 is a more versatile tool for introducing nitrogen into carbonaceous materials than previously anticipated.

Relevance of shock waves derived from asteroid impacts in the atmosphere of the early Earth in the production of compounds of astrobiological interest

Abstract The generation of organic compounds relevant to the origin of living beings is easily achieved if reducing conditions exist in the environment; however, proposed models of primitive atmospheres do not favour these conditions. This work considers the quantity and possible size of the cosmic bodies that could have impacted the Earth between 4.2 and 3.8 Ga. Different atmospheres (with gases such as CO2, CO, N2, CH4) were experimentally irradiated by an Nd-YAG laser (used to simulate the energy of a shock wave produced by the interaction of a cosmic body with the atmosphere). Although the main products are short-chain, saturated and unsaturated hydrocarbons, hydrogen cyanide (HCN) is the most abundant in some atmospheres. HCN is an important precursor of the organic molecules relevant to chemical evolution. According to our calculations, between 1023 and 1025 g of HCN could have been produced by the energy released to the atmosphere from the entry of cosmic objects between 4.2 and 3.8 Ga. Therefore, this shock wave energy could play an important role in the processes of chemical evolution.

Cost-effective approach for atmospheric accretion reactions: a case of peroxy radical addition to isoprene.

We present an accurate and cost-effective method for investigating the accretion reactions between unsaturated hydrocarbons and oxidized organic radicals. We use accretion between isoprene and primary, secondary and tertiary alkyl peroxy radicals as model reactions. We show that a systematic semiempirical transition state search can lead to better transition state structures than relaxed scanning with density functional theory with a significant gain in computational efficiency. Additionally, we suggest accurate and effective quantum chemical methods to study accretion reactions between large unsaturated hydrocarbons and oxidized organic radicals. Furthermore, we examine the atmospheric relevance of these types of reactions by calculating the bimolecular reaction rate coefficients and formation rates under atmospheric conditions from the quantum chemical reaction energy barriers.

Copper(I) complexes bearing pyrrole-bridged S,N and N-donor ligands as catalysts for tandem hydroamination-alkynylation: effect of anions on product formation.

In this study, the reaction between 2-(3,5-dimethylpyrazolylmethyl)-5-(dimethylaminomethyl)pyrrole and thiophenol under heating conditions afforded the new ligand 2-(3,5-dimethylpyrazolylmethyl)-5-(phenylthiomethyl)pyrrole 2. The reaction of 2 with meta-chloroperbenzoic acid provided sulfoxide 3 and sulfone 4 group-containing ligands. The reaction of 2 with copper(I) halides provided the binuclear complexes [Cu(μ-X){μ-C4H3N-2-(CH2Me2pz)-5-(CH2SPh)-κ2-S,N}]2 (X = Cl, Br and I, 5-7) in high yields. Conversely, the analogous reaction of 4 with copper(I) halides yielded two types of complexes, three coordinate bi- and mononuclear of the type [Cu(μ-Cl){C4H3N-2-(CH2Me2pz)-5-(CH2SO2Ph)-κ1-N}]28 and [CuX{C4H3N-2-(CH2Me2pz)-5-(CH2SO2Ph)-κ1-N}2], X = Br, 9 and I, 10. When the reaction was carried out in the presence of KPF6, the two-coordinate complex [Cu{C4H3N-2-(CH2Me2pz)-5-(CH2SO2Ph)-κ1-N}2]PF6-11a was isolated, whereas its BF4- analogue 11b was synthesized by the reaction of 8 with AgBF4. The structures of these complexes were determined using single-crystal X-ray crystallography. These copper complexes catalyzed the hydroamination-alkynylation reaction between several secondary amines and alkyl and aryl terminal alkynes. Using 1 mol% of complexes 5-10 as catalysts, both tri- and tetra-substituted propargylamines were isolated. Alternatively, phenylacetylene and different secondary amines afforded the corresponding trisubstituted propargylamines as the major products and alkyl terminal alkynes gave the tetrasubstituted products in excellent yields. In addition, the role of counter anions such as TfO-, PF6-, BF4-, PO43- and Ph4B- on the product selectivity was studied. When fluorinated anions such as TfO-, PF6-, and BF4- were present with the copper complexes, the hydroamination-hydrovinylation product 1-aminodiene 23 was observed, which was not formed with PO43-, Ph4B- or halide ions. Specifically, TfO- and PF6- favored the formation of 23, while BF4- favored the tetrasubstituted product as the major product. This was further supported by the isolated copper(I) complexes containing PF6- and BF4- and by other specific reactions. The peaks for enamines and [LCu]+ species in the HRMS spectra of the reaction mixtures and the isolation of the morpholinium copper(I) salt support the proposed mechanism.

Photocatalyzed dehalogenative deuteration with silacarboxylic acids as halogen-atom transfer agents

A visible light-induced organophotocatalytic strategy for dehalogenative deuteration of a wide variety of primary, secondary, and tertiary alkyl bromides is reported.

Nickel-catalyzed C(sp2)-C(sp3) coupling via photoactive electron donor-acceptor complexes.

We have developed a novel Ni-catalyzed reductive cross-coupling reaction of aryl bromides and alkyl iodides via a photoactive electron donor-acceptor (EDA) complex. This photo-induced process enables the efficient construction of C(sp2)-C(sp3) bonds in the absence of an external photocatalyst. Electronically and structurally diverse aryl bromides, as well as secondary and primary alkyl iodides could undergo this transformation smoothly. Natural product derivatives were employed successfully, and UV-vis spectroscopy was utilized to gain mechanistic insight.