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Cannabinol (CBN), an oxidation product of THC, is a minor cannabinoid that displays a wide range of medicinal properties with less psychoactive effects. Traditionally, CBN derivatives are synthesized from terpenoids and resorcinol derivatives using a complex multistep process, involving Friedel-Crafts alkylation, cyclization, and aromatization. In this study, we propose that iodine could serve as both a Lewis acid catalyst and an aromatization agent. As a result, a convenient one-pot iodine-mediated reaction between (1 S ,4 R)- p -menthadienol and substituted resorcinol was developed. Various reaction parameters were explored, and the yields were assessed using quantitative 1H NMR. The optimized conditions gave a 71 % isolated yield of 3-(1′,1′-dimethylheptyl)cannabinol (DMH-CBN) as a model substrate. Further investigation of the substrate scope demonstrated that this one-pot iodine-mediated synthesis could provide alkyl-substituted CBN derivatives in isolated yields ranging from 28 % to 63 %, including the C3-unsubstituted CBN, which could undergo bromination to give novel 4-bromo and 2,4-dibromo derivatives in high yields. Citral was also successfully used in place of (1 S ,4 R)- p -menthadienol as an inexpensive alternative starting material to give the natural CBN in 22 %. These newly synthesized CBN derivatives were studied for their protective effects on the intestinal epithelial barrier using the transepithelial electrical resistance (TER) assay, suggesting that the 2,4-diethyl, 4-bromo, and 2,4-dibromo derivatives of C3-unsubstituted CBN exhibited superior activity compared to natural CBN with low toxicity. This indicates their potential as novel candidates in the cannabinoid series, contributing to the anti-inflammatory activity. [Display omitted] • A simple, one-pot synthesis of cannabinol (CBN) and derivatives was developed. • Iodine acts as both a Lewis acid catalyst and aromatizing agent. • CBN derivatives were synthesized in 1 h with isolated yields ranging from 28 % to 71 %. • New CBN derivatives were identified as potential anti-inflammatory candidates with low toxicity. [ABSTRACT FROM AUTHOR]

An efficient Brønsted acid catalyzed formal (3 + 2) annulation reactions of 3-hydroxy-3-phenacyloxidole derivatives with 2-naphthols and activated phenols has been developed. This formal (3 + 2) annulation involved a dehydration/Friedel-Crafts alkylation/hemiketalization/dehydration cascade process, and afforded a variety of highly functionalized oxindolyl-naphthofurans with good yields. Moreover, some of the obtained products were tested against a panel of cancer cell lines, and one compound was identified to inhabit the proliferation of some cancer cell lines, thus indicating that such skeletons might server as leading compounds with antitumor activity. [Display omitted] • A formal (3 + 2) annulation reaction of 3-hydroxy-3-phenacyloxidole derivatives with 2-naphthols and activated phenols was established by the Brønsted acid catalyst. • This formal (3 + 2) annulation involved a dehydration/Friedel-Crafts alkylation/hemiketalization/dehydration cascade process, the strategy allowed the preparation of highly functionalized oxindolyl-naphthofuran scaffolds. • Moreover, we have done the bioactivity evaluation of the compounds, and one of the obtained products was identified to inhibit the proliferation of some cancer cell lines, thus indicating that such skeletons might serve as leading compounds for the development of antitumor drugs. • In situ construction of diverse oxindolyl-naphthofuran scaffolds with moderate to high yields. One of the products can inhibit the proliferation of some cancer cell lines. [ABSTRACT FROM AUTHOR]

β-Pinene, unlike α-pinene, is easily and quantitatively metalated with butyllithium/TMEDA. The resulting allyllithium•TMEDA is easily isolated, with the racemic material crystallizing preferentially, even from 92 % ee solutions. The complex is indefinitely stable in C 6 D 6 , and has been fully characterized. Reaction with formaldehyde favors alkylation at the less substituted allyl position with modest regioselectivity (2:1), and the corresponding Grignard reagent (made by transmetalation with MgBr 2) reacts very regioselectively at the more substituted position with formaldehyde and diphenyl disulfide (99-92 %, resp.). The two phenyl sulfide isomers are observed to equilibrate when exposed to heat or UV light. This easy metalation provides access to a versatile chiral-pool-derived allyl nucleophile. [Display omitted] • Readily accessible chiral (92 % ee) allylmetallic. • Dramatic regiochemical outcomes between Li and MgX. • Unexpected equilibration of allyl phenyl sulfide regioisomers. [ABSTRACT FROM AUTHOR]

The chiral pool material carvone available in both enantiomer forms have been extensively used in total syntheses of various natural products. Different strategies have been developed considering the available structural features in both the enantiomers of carvone. The enone present has been remarkably used for epoxidation, conjugate addition, γ-oxygenation, reductive alkylation, etc. The six-membered ring has been contracted for arriving at the functionalized 5-membered ring moiety present in many natural products. Further, the carvone skeleton has been readily modified to advanced intermediates available for Friedel-Crafts alkylation, annulations, coupling reactions, metathesis and both inter- and intramolecular cyclizations. This review focused on various strategies developed using the carvone scaffold in total syntheses of different natural products in the period 2016 to 2023. [Display omitted] [ABSTRACT FROM AUTHOR]

A method for synthesizing polycyclic quinazolinone derivatives with ketoalkyl substitutions has been developed through strong acid-catalyzed radical tandem alkylation/cyclization of unactivated alkenes with readily available ketones under microwave irradiation. The transformation offers several advantages, including wide functional group compatibility, operational simplicity, and moderate to good yields. This methodology offers an appealing approach to obtaining keto-containing polycyclic quinazolinones with pharmaceutical value. [Display omitted] A method for synthesizing polycyclic quinazolinone derivatives with ketoalkyl substitutions has been developed through strong acid-catalyzed radical tandem alkylation/cyclization of unactivated alkenes with readily available ketones under microwave irradiation. The mechanistic studies revealed that the strong acid-catalyzed tandem alkylation/cyclization occurs through a radical pathway. This approach provides a potential route for the functionalization of quinazolinones that may find wide applications in pharmaceutical preparation. [ABSTRACT FROM AUTHOR]

The synthesis of cyclopropanes by the cyclization of allylic diazoesters is well-known. In prior studies toward the sesquiterpenoid euonyminol, we attempted to carry out an intramolecular cyclopropanation of an allylic diazoester containing an electronically-unbiased alkene embedded in a 6-oxa-bicyclo[3.2.1]-oct-3-ene skeleton. We obtained exclusively a product arising from 1,2-addition of oxygen and carbon (oxyalkylation) to the alkene. While oxyalkylation products have been reported when electron-rich alkenes (e.g. enol ethers) are employed, oxyalkylation products derived from electronically-unbiased alkenes are rare. Here, we establish that the oxyalkylation is general for a range of 6-oxa-bicyclo[3.2.1]-oct-3-ene substrates and show that these products form competitively in the cyclization of simpler α-diazo-β-ketoesters. Our data suggest increasing charge separation in the transition state for the addition promotes the oxyalkylation pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

The Enolates of hexahydro-3,4-dioxa-8a-aza- as -indacen-2-ones can react with electrophiles in a substrate-controlled fashion to create a new stereogenic center positioned beta to the N-pyrrolidinyl moiety. Preferential diastereoselective reactions predominantly proceeded from the convex face of the enolates, yielding stereospecific alkylated or halo-substituted products with high yields and exceptional diastereoselectivities. Di-substituted compounds were obtained by the alkylation or halogenation of the enolates of the corresponding mono-substituted compounds. Total synthesis of (−)-indolizidine 195G was also accomplished. © 2024 Elsevier Science. All rights reserved. [Display omitted] [ABSTRACT FROM AUTHOR]

In this work, a recyclable and highly regioselective 1,6-hydroarylation of para -quinone methides (p -QMs) with N -heteroarenes has been developed under mild conditions. 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) as a solvent plays a significant role in this transformation to achieve a wide assortment of unsymmetrical triarylmethanes with high yields and excellent regioselectivity. This novel reaction is featured a very broad substrate scope and outstanding functional group tolerance and could also be scaled-up. Moreover, this Friedel-Crafts alkylation pathway is further supported by replacing HFIP with trifluoroethanol (TFE) in the control reactions. A highly regioselective 1,6-hydroarylation of para -quinone methides (p -QMs) with N -heteroarenes has been developed under mild conditions. 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) as a solvent plays a significant role in this transformation to achieve a wide assortment of unsymmetrical triarylmethanes with high yields and excellent regioselectivity. Moreover, this transformation can be easily extended to a gram scale-synthesis level. [Display omitted] [ABSTRACT FROM AUTHOR]

A facile and efficient method for the synthesis of chromone-containing triarylmethane derivatives via a HFIP promoted tandem alkylation/annulation protocol of o -hydroxyaryl enaminones with chlorohydrocarbon is described. Employing DCM/HFIP as solvent, the reactions proceed smoothly at room temperature without any transition-metal catalyst, providing a variety of chromone-containing triarylmethanes in moderate to good yields. Moreover, the developed protocol reveals a broad substrate scope and good group tolerance. [Display omitted] [ABSTRACT FROM AUTHOR]

A mild and efficient catalyst system for asymmetric Friedel-Crafts alkylation of indoles with trifluoropyruvates was reported. The chiral ligands took the advantages of both the proline and the binaphthyl moieties, and the in situ prepared Cu(II) catalyst showed good substrate tolerance in the reactions. Indoles bearing different substituents could be tolerated, and the desired products could be obtained in up 99 % yields and up to 98 % ee. Especially, the reactions could be carried out in gram scale without the loss of stereoselectivity, and some of products were able to achieve 99 % ee after simple crystallization. [Display omitted] • New catalyst system combining the advantages of both the binaphyl and the proline moieties. • Good scalability. • Mild reaction conditions. • High yields and high enantioselectivities. [ABSTRACT FROM AUTHOR]

This article describes the synthesis of optically pure four N -Boc and N -Cbz-protected (R) - and (S) - isomers of Garner's aldehyde. The key step involves TiCl 4 -catalyzed Evans' aldol reaction of the uncommon chiral synthon "glycine enolate equivalent" of N-(N -Boc/Cbz-glycinyl) oxazolidinone with gaseous formaldehyde. The chromatographically separable Evans and non-Evans adduct formation takes place through the installation of hydroxymethyl functionality on chiral glycine enolate in good yields. The orthogonality of the reaction was maintained via the "reverse addition" in the aldol reaction on Evans chiral auxiliary. This method provides a promising opportunity for the synthesis of expensive (R)-Garner's aldehyde evading the use of unnatural d -serine. Moreover, asymmetric alkylation of Li-enolate of N-(N- Boc-glycinyl) oxazolidinone is a promising opportunity for the formation of an exclusive single isomer of (R)-Garner's aldehyde. [Display omitted] [ABSTRACT FROM AUTHOR]

The development of a nickel-catalyzed C–H alkylation of aromatic substrates with unactivated alkyl halides is described. This carbocyclization facilitates the synthesis of diverse fused ring systems from simple aromatic substrates and is an attractive alternative to traditional polar or radical-mediated ring formations. The present system uses unactivated primary and secondary alkyl bromides and chlorides, while avoiding the use of precious palladium catalysts and more reactive alkyl halides commonly used in related C–H alkylations. Image 1 [ABSTRACT FROM AUTHOR]

Aliphatic acid anhydrides are the versatile building blocks and the new method for the conversion of anhydrides is thus of great significance. Herein, we report the decarboxylative alkylation of aryl triflates with aliphatic acid anhydrides via nickel catalysis. This novel method provides a facile access to construct Csp2-Csp3 bond. In addition, this method is compatible with a broad array of functional groups and exhibits good substrates scope. Image 1 [ABSTRACT FROM AUTHOR]

A chemoselective domino annulation reaction of β-naphthols with methyl aryldiazoacetate is described. The gold catalyst promoted C–H functionalization of β-naphthols, whereas a rhodium or copper complex led to O–H insertion reactions. Consecutive intramolecular lactonization occurred after site-selective alkylation at the 1-position of β-naphthol, providing functionalized naphthofuranone derivatives. The product was transformed into a chiral molecule bearing an all-carbon quaternary stereogenic center with high enantioselectivity. Image 1 [ABSTRACT FROM AUTHOR]

Abstract In this review, cross-coupling reactions by cooperative Pd/Cu or Ni/Cu catalysis based on catalytically generated organocopper nucleophiles are summarized. Compared to conventional methods based on the use of stoichiometric amounts of pre-synthesized organometallic reagents, these methods are powerful tools for the alkynylation, arylation, alkenylation, and alkylation of organic electrophiles, especially as they can be carried out in a highly step-economical manner with readily available starting materials based on simple arenes, carboxylic acids, alkenes, and alkynes as pre-nucleophiles. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract Two procedures for the synthesis of barely accessible 8-chloro-3,4-dihydroisoquinoline were investigated. The first approach is based on a directed ortho -lithiation of N -pivaloyl meta -chlorophenylethylamine, followed by formylation and subsequent ring closure under acidic conditions. In the second, more advantageous variant, the N -hydroxyethyl ortho -chlorobenzylamine intermediate undergoes a Friedel-Crafts reaction, and the resulting tetrahydro derivative is oxidized with N -bromosuccinimide. The 8-chloro-3,4-dihydroisoquinoline key intermediate is then applied in Suzuki reactions to give various 8-aryl-3,4-dihydroisoquinolines, which are finally treated with alkyl or aryllithiums to give 1-substituted 8-aryl-1,2,3,4-tetrahydroisoquinolines. These novel 1,2,3,4-tetrahydroisoquinoline derivatives can be used as building blocks in the synthesis of potential drug candidates. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

We have developed a FeCl 3 -catalyzed protocol for the Friedel-Crafts alkylation of 2-substituted furans with 2-nitrobenzhydrols. The described method allows for synthesizing 2-(2-nitrobenzyl)furans in good to high yields. We also demonstrated the synthetic utility of obtained 2-(2-nitrobenzyl)furan, which could be used for the synthesis of substituted oxazino[2,3- a ]indole. [Display omitted] [ABSTRACT FROM AUTHOR]

A synthesis route which passes through a trans -4-arylchroman-3-ol intermediate en route to the total synthesis of the marine natural product ammonificin A was designed and pursued. Initial model studies were focused on the development of suitable method for constructing trans -4-arylchroman-3-ol core and then its conversion into cis -3-aryloxy-4-arylchromane scaffold. In this context, a new strategy has been developed to prepare trans -4-arylchroman-3-ols bearing ortho / para -EDG in the C-4 aryl group via intramolecular dehydrative Friedel–Crafts alkylation of 3-aryloxy-1-arylpropane-1,2-diols. A number of attempts to convert trans -4-arylchroman-3-ols into cis -3-aryloxy-4-arylchromans failed. This problem was successfully overcome using diphenyliodonium tetrafluoroborate for the O -arylation of a cis -4-arylchroman-3-ol intermediate. Notwithstanding these noteworthy accomplishments, the first total synthesis of ammonificin A remained elusive as the planned applications of these two newly developed methodologies for the total synthesis was disastrous because commonly used reaction conditions unexpectedly thwarted the deprotection of an acetonide moiety of early-stage intermediates. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract The synthesis of a 1,2,9,9a-tetrahydrocyclopropa[ c ]benz[e]indol-4-one (CBI)-adenine adduct via regioselective N-3 alkylation of adenine with a 1-(iodomethyl)-2,3-dihydro-1 H -benzo[e]indol-5-ol (I-seco-CBI)-containing precursor is described. Spectroscopic analyses of the unlabeled and adenine-C8 carbon-13 labeled adducts utilizing ROESY NMR techniques allowed structural assignment of the alkylation product as the adenine N-3 substituted regioisomer. A stable-isotopically labeled version of the N-3 adduct incorporating six carbon-13 labels was also prepared by this method for use as an LC-MS internal standard. The cyclized CBI-containing compound was also found to alkylate adenine at elevated temperatures to produce the N-3 adduct albeit at a significantly slower rate than that observed for the I-seco-CBI precursor. Adenine alkylation with an I-seco-CBI precursor offers scalable and facile access to a CBI-adenine adduct facilitating its use as an efficacy marker for the development of duocarmycin-based ADCs. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract A novel and efficient Ni-catalyzed aryl- and alkyl-selenation of imidazo[1,2-α]pyridines employing selenium powder has been developed for the first time. The significant advantages of this protocol are that it is an inexpensive nickel catalyst and exhibits broad functional-group compatibility and good reaction yields. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract During our research looking for novel inverse agonists of RORγt, we identified a potent sulfoximine-based modulator as one of our pre-clinical candidates for the topical treatment for psoriasis. Herein, we describe the various routes we evaluated during the lead generation and optimization phases and the final route chosen for scale-up to deliver the first 100 g of API. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract An expedient approach for the intermolecular C-H functionalization of pyrazines and other heteroarenes by the radical chemistry of xanthates is reported. Incorporation of a multitude of functional alkyl groups onto these heteroarenes proceeds in good yield and good to excellent regioselectivity, leading to highly functionalized heteroaromatics. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract A sustainable route for the N -1 alkylation of imidazole and benzimidazole derivatives has been developed under volatile organic solvent free condition in alkaline water-SDS system. Incorporation of SDS in the reaction medium enhances the reaction rate by suppressing the solubility issue that arises for different substrates. This method provides high yield of the alkylated product in a shorter reaction time. For reactive alkyl halides reaction proceeds at ambient temperature whereas in the cases of less reactive alkyl halides require 55–60 °C to complete alkylation process. N -alkylation induced ring opening of the heterocyclic ring in benzimidazole derivatives to multifunctional aromatic compounds were noticed at 60 °C when more than two equivalents of alkyl halide was used. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract We report the rapid synthesis of various cycloheptane-fused chromones and an oxepine fused flavone in 5 steps from the corresponding 2-hydroxy acetophenone. Furthermore, we describe the synthesis of xanthones, in moderate to good yield, from 2,3-disubstituted flavones using a Friedel Crafts alkylation strategy. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

The title compounds were synthesized from the selectively protected N -acylated d -glucosamine derivatives, containing α-halo carboxylic acid moieties, via intramolecular 3- O -alkylation. It was found that if the starting compound contains asymmetric electrophilic center, isomuramic acid derivatives were mainly formed, regardless of the configuration of the electrophilic carbon atom. An explanation for the observed stereochemical results was proposed on the basis of the analysis of steric interactions in the molecules of the starting compounds, as well as using the concept of anchimeric assistance. It was shown that N -acetylation of the obtained lactam derivatives and subsequent methanolysis under mild conditions led to the selective cleavage of δ-lactam ring resulting in the formation of the corresponding ester derivatives of N -acetylmuramic acid or its analogues in high yields. [ABSTRACT FROM AUTHOR]

A convenient, practical and highly efficient one-pot method has been developed for the synthesis of triaryl- and triheteroarylmethane derivatives by Bi(OTf) 3 -catalyzed Friedel-Crafts alkylation of trialkyl orthoformates in combination with a wide variety of arenes/heteroarenes at room temperature under solvent-free conditions and in an air atmosphere. The methodology offers an operational simplicity, high atom economy and environmentally benign procedure. Furthermore, selected compound 3k showed promising anti-inflammatory activity with inhibition nitric oxide and did not exhibit significant cytotoxic effects on macrophage cells. [ABSTRACT FROM AUTHOR]

We report herein the intramolecular α- tert -alkylation of unsaturated β-ketoesters which gives rise to highly functionalized cyclopentanes. This transformation is characterized by its operational simplicity, mild reaction conditions and the use of scandium (III) triflate as a Lewis acid catalyst. Of interest, cyclopentanes bearing heterocycles, sites for post reaction functionalization and spirocyclic architectures are accessible with this strategy. [ABSTRACT FROM AUTHOR]

Friedel-Crafts reaction of 1-( N -acylamino)alkyltriarylphosphonium salts with arenes or heteroarenes without the need for any catalyst provided access to a wide range of biologically interesting N -(1-arylalkyl)amides or 1-arylalkylphosphonium salts which can be of great interest in the chemistry of ylides and phosphonium ionic liquids. Depending on reaction conditions and substrate structure, the reaction can be conducted selectively with high yields toward each of the above-mentioned products. Mechanistic aspects of the above transformations were also considered. [ABSTRACT FROM AUTHOR]

An I 2 -mediated Friedel-Crafts alkylation/oxidative coupling reaction of indoles and salicylaldehydes was developed. With the developed protocol, a series of indolylchromeno[2,3- b ]indoles were obtained in good yields (up to 88%) under mild reaction conditions. Two possible reaction mechanisms were tentatively brought forward to account for the formation of the products in light of some control experiments. [ABSTRACT FROM AUTHOR]

A useful and efficient method to construct diversely substituted 1,2,3,4-tetrahydroquinolines in good to excellent yields has been developed through a catalyst-free Domino Mannich and intramolecular Friedel-Crafts alkylation reactions of N -arylamines with paraformaldehyde and electron-rich olefins via the formation of N -aryl- N -alkylmethyleneiminium ions as the key intermediates to afford the target products. Nine of the new compounds were evaluated in the US National Cancer Institute (NCI), where compound 5f (R1 = 6-MeO, R2 =  p -ClC6H4 and X = pyrrolidin-2-onyl) presented a remarkable activity against 57 cancer cell lines, with the most important GI50 values ranging from 1.46 to 8.28 μM from in vitro assays. Further studies performed over the active compound 5f on HCT116 colon cancer cells indicated that its effect on cell death is exerted through a cell cycle arrest (S phase) in a dose dependent manner, as well as suppression on the cell proliferation process. [ABSTRACT FROM AUTHOR]

Birch's reductive alkylation of biphenyl-4-carbonitrile ( 1 ) provides alkylated 1,4-dihydroderivatives of various structural types: 4-alkyl-4-phenylcyclohexa-2,5-dienone, 1,4-dialkyl-4-phenylcyclohexa-2,5-dienecarbonitrile (with the same or different alkyl fragments), and 4-(1-alkylcyclohexa-2,5-dienyl)benzonitrile. Each of these products become dominant depending on the nature of long-living anionic form generated from 1 , namely, the stable product of two-electrons reduction – dianion ( 1 2− ); 1-alkyl-4-cyano-1-phenylcyclohexa-2,5-dien-4-yl anion ( 1-Alk 1 – ), originated due to the alkylation of dianion 1 2− at the position 1 of biphenyl moiety; or 1-(4-cyanophenyl)cyclohexa-2,5-dien-1-yl anion ( 1-H 4’ – ), being the product of dianion 1 2− protonation at position 4′ by protonating reagent (MeOH or NH 4 Cl). The orientation of alkyl fragment incorporation into biphenyl-4-carbonitrile scaffold is in agreement with calculated electronic structure of the anionic species under investigation. The dominating type of their reactivity towards alkyl halides proved to be nucleophilic ( S N 2 mechanism). [ABSTRACT FROM AUTHOR]

Phenoxathiin-based thiacalix[4]arene, obtained by the acid-catalysed rearrangement of the corresponding spirodienone derivative, was immobilized using the alkylation with chloroacetonitrile to yield three (out of four theoretically possible) stereoisomers. As the conformational outcome of the reaction could not be unambiguously assigned using standard NMR techniques, the method of Residual Dipolar Coupling constants (RDCs) was applied. The measuring of an anisotropic through-space dipole-dipole interactions in the lyotropic liquid crystalline alignment medium (PELG, poly-γ-ethyl- l -glutamate, and PBLG, poly-γ-benzyl- l -glutamate) enabled the assignment of the individual conformers. The usefulness of this approach was finally confirmed by the X-ray crystallography data. [ABSTRACT FROM AUTHOR]

This paper includes the synthesis of 2-(1,3-dioxane-2-yl)ethyl substituted benzimidazole substituted N -heterocyclic carbenes precursors and their ruthenium complexes. Synthesized compounds were characterized by elemental analysis and NMR spectroscopy. All complexes have been tested in the alkylation of pyrrolidine and morpholine with alcohols, showing an excellent activity in this reaction. [ABSTRACT FROM AUTHOR]

The reaction of methyl iodide with tert -butylphenylsulfide in DMF leads to a transalkylation that produces methylphenylsulfide. This transalkylation reaction was further studied by 1 H NMR spectroscopy. The polarity of the solvent, the electron density on the sulfur atom, and the strength of the alkylating agent (MeI, EtI, BuI, dimethyl sulfate, or dimethyl carbonate) played important roles in the reaction. The suggested mechanism of the reaction involves the formation of a dialkyl aryl sulfonium salt that subsequently eliminates the radical. This mechanism was supported by the observation of higher conversion rates for compounds with more branched alkyl groups on the sulfur atom, which may lead to the formation of more stable radicals. [ABSTRACT FROM AUTHOR]

A CuBr 2 -catalyzed alkylation of furans with a broad scope of benzyl alcohols and benzaldehydes is reported. Reaction proceeds efficiently under mild reaction conditions requiring no inert atmosphere or other precautions. Moreover, it is shown that CuBr 2 catalyzes domino reactions of furans with benzyl alcohols or benzaldehydes bearing a nucleophilic moiety in the ortho -position. These protocols offer a practical approach to densely substituted heterocyclic motifs from easily available furans. [ABSTRACT FROM AUTHOR]

Herein, we report the first examples of the Mitsunobu alkylation of β -alkoxycarbonyl 2-nitrobenzenesulfones. Wang resin was acylated with α-halocarboxylic acids followed by the reaction with 2-nitrothiophenols. After oxidation with m -chloroperbenzoic acid, the immobilized β -alkoxycarbonyl 2-nitrobenzensulfones were subjected to alkylation with various alcohols. The reaction outcome strongly depended on the selection of the alkylating species. After the reduction of the nitro group, acid-mediated cleavage and subsequent cyclization, the C 2 -(di)substituted benzothiazin-3(4 H )-one 1,1-dioxides were obtained in high crude purities and good overall yields. [ABSTRACT FROM AUTHOR]

The rhodium(III)-catalyzed C−H alkylations of indolines with enones and enals is described. This reaction can proceed through 1,4-conjugate addition and protonation process providing β-indolinic ketone compounds, which are known to be crucial scaffolds of biologically active compounds. [ABSTRACT FROM AUTHOR]

A selective N -alkylation reaction of 2-pyridones and related heterocycles via intermolecular alkene hydroamination is reported. The reaction utilizes palladium(II) acetate as a catalyst and employs a bidentate directing group to dictate the regioselectivity for both unactivated terminal and internal alkenes. High functional group tolerance is observed across a widerange of electronically diverse 2-pyridones and other aza-heterocycles, including 1-hydroxyisoquinoline, 2-hydroxyquinoline, pyridazinone, pyrimidinone, and pyrazinone. [ABSTRACT FROM AUTHOR]

Structural revision of glabramycin B, which is an antibacterial 10-membered lactone isolated from a fermentation broth of Neosartorya glabra , was achieved by enantioselective synthesis of our proposed structure. The correct structure of glabramycin B was presumed on comparison with related compounds, and synthesis of it was succeeded via dianion alkylation, Shiina's lactonization and Stille cross-coupling. By this synthesis, we were able to correct the reported structural misassignment, and to confirm the relative configuration of glabramycin B to be 10 S *,11 S *,15 R *,20 S *. [ABSTRACT FROM AUTHOR]

An efficient catalytic system containing [RuCl 2 (η 6 -p-cymene)] 2 and one P,N ligand, N-diphenylphosphino-2-aminopyridine ( L1 ) was loaded in catalyzing the alkylation of ketones with primary alcohols for a diverse array of substrates. Other five P,N ligands based on pyridin-2-amine and pyrimidin-2-amine were also examined in this reaction to explore the influence of steric hindrance and electronic effects. Monitoring by 1 H NMR and ESI-MS reveals a stable cationic L1 -coordinated ruthenium hydride intermediate, identified as [Ru(η 6 -p-cymene)(κ 2 - L1 )H] + . Organic intermediates consistent with a three-step dehydrogenation, alkylation and hydrogenation pathway were also observed. The final step in this reaction, the ruthenium-catalysed transfer hydrogenation reduction of α,β-unsaturated ketone with benzyl alcohol was performed separately. [ABSTRACT FROM AUTHOR]

Simple pyrazole based palladacycle-phosphine with a high turnover has been developed and applied for the N-alkylation of amines and sulfanilamide using alcohols as substrates by hydrogen borrowing strategy. N-alkylation of primary and secondary amines resulted in high isolated yields at 100–130 °C, under solvent free conditions. More challenging secondary aliphatic as well as aromatic alcohols were also successfully utilized as alkylating agents under similar reaction conditions. The turn over number reached up to 43000 for N-benzylation of aniline using benzyl alcohol. Notably, regioselective N-alkylation of 2-aminobenzothiazole and 4-aminobenzenesulfonamide to the corresponding 2-N-(alkylamino)azoles and 4-amino-(N-alkyl)benzenesulfonamides using alcohols as alkylating agents have been achieved using our new pre-catalyst-phosphine system. [ABSTRACT FROM AUTHOR]

A Cs 2 CO 3 -catalyzed alkylation reaction of indoles with trifluoromethyl ketones was presented. Both alicyclic and aromatic trifluoromethyl ketones as well as various substituted indoles are compatible with the methodology. Good to excellent yields of the corresponding trifluoromethyl substituted tertiary alcohols 2,2,2-tritrifluoro-1-(1H-indol-3-yl)-ethan-1-ols were acquired as the sole products. [ABSTRACT FROM AUTHOR]

Flow chemistry enables the preparation of bis(indolyl)methanes from various indoles and structurally divergent aldehydes using Sc(OTf) 3 catalysis. The reaction is regioselective for C-3 functionalization of the indoles, occurring over short reaction times allowing for rapid investigation of scope with straightforward work up facilitating product isolation. [ABSTRACT FROM AUTHOR]

The synthetic utility of 2-mercaptonicotinonitriles 3 and 4 , as well as 2-mercapto-4-oxo-6-phenyl-1,4-dihydropyrimidine-5-carbonitrile 20 as building blocks for novel bis- and poly(pyridines), along with poly(pyrimidines) via alkylation with the corresponding bis- and poy(halo) compounds was investigated. Spectroscopic and theoretical studies confirmed the S -alkylation rather than the N -alkylation. [ABSTRACT FROM AUTHOR]

Base Mediated Michael addition of 1,3-dicarbonyl compounds to α-halodicyclopentadienones followed by cyclization of the intermediate Michael adducts leads to novel annulated dihydrofurans as single diastereomers. Such fused dihydrofurans, which are also oxa-triquinanes and oxa-diquinanes, undergo retro-Diels-Alder reaction to give cyclopentadiene-eliminated products in excellent yield. Certain 1,3-dicarbonyl compounds exhibited a different reactivity profile with α-halodicyclopentadienones leading to spiro-cyclopropanes fused to dicyclopentadiene skeleton. [ABSTRACT FROM AUTHOR]

Non-volatile S -Alkyl- S -phenyl-2,3,4,5-tetramethylphenylsulfonium triflate or tetrafluoroborate salts have been used to alkylate alcohols in the presence of sodium hydride. This is a simple and efficient method for the synthesis of ethers from complex alcohols and an alternative to the usual O -alkylation methods. This method was especially important for the preparation of monofluoromethyl ethers of a wide range of alcohols. Some alkylated derivatives of the precursors of some bioactive compounds were also prepared using these reagents. [ABSTRACT FROM AUTHOR]

Total synthesis of myriocin and mycestericin D was achieved using the Du Bois Rh(II)-catalyzed C H amination of a sulfamate and subsequent alkylation as a key step. The reaction of a sulfamate with PhI(OAc) 2 and MgO in the presence of Rh 2 (OAc) 4 gave oxathiazinane N , O -acetal as the sole product in high yield. Alkylation of N , O -acetal using vinylmagnesium bromide in the presence of ZnCl 2 proceeded stereoselectively to provide an oxathiazinane bearing a quaternary chiral center in high yield. Myriocin and mycestericin D were synthesized from a common synthetic intermediate. This route includes the first application of the Du Bois procedure for constructing a quaternary chiral center. [ABSTRACT FROM AUTHOR]

The asymmetric α-allylation of 3-pentanone using several different N -amino cyclic carbamate (ACC) auxiliaries is described. The level of asymmetric induction was found to range from er = 93:7 to er = 99:1. The factors that lead to compromised selectivity for the various auxiliaries have been determined. Significantly, we have established that using the easily accessible and inexpensive valine-derived ACC auxiliary, it is possible to obtain synthetically useful levels of asymmetric induction ( er = 96:4). [ABSTRACT FROM AUTHOR]

A series of diverse polycyclic heterocycles containing 3-hydroxyoxindole, and alkyliminofurochromone fused rings have been synthesized through the uncatalyzed Friedel-Crafts hydroxyalkylation of 3-(alkylamino)-9 H -furo [3,4-b]chromen-9-ones generated in situ by the [4 + 1] cycloaddition/tautomerization of alkyl isocyanides and 3-formylchromones with isatin derivatives. The method is simple and provides a new class of pharmacologically important furochromone-isatin conjugates in moderate to good yields. The products bearing two contiguous stereogenic centers and one stereogenic group were obtained in excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]