Search Results (23)

Lupeol, a naturally occurring pentacyclic triterpenoid widely distributed in various medicinal plants, has attracted significant attention due to its diverse pharmacological properties. In this study, we report the synthesis and structural modification of 14 lupeol derivatives through selective functionalizations at C3 and C30 positions of the lupane skeleton, via the sequential chemoselective introduction of carbonyl moieties and the addition of organometallics. Emphasis has been given to the stereoselective alkylation at C3 using a range of carbanions, including organolithiums, organomagnesiums and organoindiums. The C30 position was modified through oxidative pathways to introduce several functionalities. Full article

Many linear diarylpentanoids and diarylheptanoids contain a β-hydroxy ketone or 1,3-diol functionality as the structural motif. Reported herein is the asymmetric synthesis of (S)-daphneolone, (S)-dihydroyashabushiketol, and formal synthesis of (3S,5S)-yashabushidiol B as represented examples, employing readily accessible (3S)-hydroxy-5-phenylpentanoic acid. The (3S)-hydroxy-5-phenylpentanoic acid was conveniently prepared by the aldol addition of (R)-acetyloxazolidinone with 3-phenylpropanal affording two diastereomers which were cleanly separated by silica gel column chromatography, followed by the removal of Evans auxiliary of (3′R,4S)-imide. Then, the (S)-acid was converted to Weinreb amide as a privileged acylating agent. Three natural products with the uppermost optical purity were prepared by the treatment of organolithium or organomagnesium reagents, respectively, to the Weinreb amide used in common. We believe that this strategy provides a rapid and convergent method for constructing these classes of molecules of interest. Full article

An organolithium reagent containing a 5,6-dihydro-1,4-dithiin moiety has been herein used as homologating agent to build up a fully protected divinylcarbinol by two different synthetic procedures, respectively, based on a step-by-step approach or a tandem process. The resulting molecule contains two double bonds masked by two dithiodimethylene bridges that can be stereoselectively removed to give a E,E- or Z,Z-configured divinylcarbinol. These products could then be conveniently functionalized, for example, with hydroxyl or amino functions, for the construction of the skeleton of more complex systems. Full article

This study investigated the influence of variations in the mixing ratio of ethylene carbonate (EC) to ethyl methyl carbonate (EMC) on the composition and effectiveness of the solid electrolyte interphase (SEI) in lithium-metal batteries. The SEI is crucial for battery performance, as it prevents continuous electrolyte decomposition and inhibits the growth of lithium dendrites, which can cause internal short circuits leading to battery failure. Although the properties of the SEI largely depend on the electrolyte solvent, the influence of the EC:EMC ratio on SEI properties has not yet been elucidated. Through electrochemical testing, ionic conductivity measurements, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy, the formation of Li₂CO₃, LiF, and organolithium compounds on lithium surfaces was systematically analyzed. This study demonstrated that the EC:EMC ratio significantly affected the SEI structure, primarily owing to the promotion of the formation of a denser SEI layer. Specifically, the ratios of 1:1 and 1:3 facilitated a uniform distribution and prevalence of Li₂CO₃ and LiF throughout the SEI, thereby affecting cell performance. Thus, precise control of the EC:EMC ratio is essential for enhancing the mechanical robustness and electrochemical stability of the SEI, thereby providing valuable insights into the factors that either enhance or impede effective SEI formation. Full article

This mini-review offers a comprehensive overview of the advancements made over the last three years in utilizing highly polar s-block organometallic reagents (specifically, RLi, RNa and RMgX compounds) in organic synthesis run under bench-type reaction conditions. These conditions involve exposure to air/moisture and are carried out at room temperature, with the use of sustainable solvents as reaction media. In the examples provided, the adoption of Deep Eutectic Solvents (DESs) or even water as non-conventional and protic reaction media has not only replicated the traditional chemistry of these organometallic reagents in conventional and toxic volatile organic compounds under Schlenk-type reaction conditions (typically involving low temperatures of −78 °C to 0 °C and a protective atmosphere of N₂ or Ar), but has also resulted in higher conversions and selectivities within remarkably short reaction times (measured in s/min). Furthermore, the application of the aforementioned polar organometallics under bench-type reaction conditions (at room temperature/under air) has been extended to other environmentally responsible reaction media, such as more sustainable ethereal solvents (e.g., CPME or 2-MeTHF). Notably, this innovative approach contributes to enhancing the overall sustainability of s-block-metal-mediated organic processes, thereby aligning with several key principles of Green Chemistry. Full article

This work reports the one-pot synthesis of sterically demanding aniline derivatives from aryllithium species utilising trimethylsilyl azide to introduce amine functionalities and conversions to new examples of a common N,N′-chelating ligand system. The reaction of TripLi (Trip = 2,4,6-iPr₃-C₆H₂) with trimethylsilyl azide afforded the silyltriazene TripN₂N(SiMe₃)₂ in situ, which readily reacts with methanol under dinitrogen elimination to the aniline TripNH₂ in good yield. The reaction pathways and by-products of the system have been studied. The extension of this reaction to a much more sterically demanding terphenyl system suggested that TerLi (Ter = 2,6-Trip₂-C₆H₃) slowly reacted with trimethylsilyl azide to form a silyl(terphenyl)triazenide lithium complex in situ, predominantly underwent nitrogen loss to TerN(SiMe₃)Li in parallel, which afforded TerN(SiMe₃)H after workup, and can be deprotected under acidic conditions to form the aniline TerNH₂. TripNH₂ was furthermore converted to the sterically demanding β-diketimines ^RTripnacnacH (=HC{RCN(Trip)}₂H), with R = Me, Et and iPr, in one-pot procedures from the corresponding 1,3-diketones. The bulkiest proligand was employed to synthesise the magnesium hydride complex [{(^iPrTripnacnac)MgH}₂], which shows a distorted dimeric structure caused by the substituents of the sterically demanding ligand moieties. Full article

Two novel Sb(III) and Sb(V) peri-substituted acenaphthene phosphorus−antimony compounds were prepared. The Sb(III) compound, 1, was prepared via reacting the organolithium precursor with dichloro(p-tolyl)Stibine, and 2 was prepared by the chlorination of 1. Both 1 and 2 were characterized by multinuclear (¹H, ¹³C and ³¹P) NMR spectroscopy, and their molecular structures resolved by single-crystal X-ray diffraction. Both compounds show a dative P−Sb interaction with the antimony being the acceptor group in both cases owing to its Lewis acidity. Full article

The stereocontrolled synthesis of 1-substituted homotropanones, using chiral N-tert-butanesulfinyl imines as reaction intermediates, is described. The reaction of organolithium and Grignard reagents with hydroxy Weinreb amides, chemoselective N-tert-butanesulfinyl aldimine formation from keto aldehydes, decarboxylative Mannich reaction with β-keto acids of these aldimines, and organocatalyzed L-proline intramolecular Mannich cyclization are key steps of this methodology. The utility of the method was demonstrated with a synthesis of the natural product (−)-adaline, and its enantiomer, (+)-adaline. Full article

A chiral glycerol derivative, namely 3-amino-1,2-propanediol, was employed for as the hydrogen bond donor (HBD) in the design of a new deep eutectic solvent (DES) with choline chloride acting as the hydrogen bond acceptor (HBA). The novel mixture was characterized and unambiguously classified as a DES. Furthermore, its synthetic usefulness was demonstrated in the room-temperature n-butyllithium-addition under air to carbonyl compounds and benzyl chloride. In some cases, pure products (100% conversion) were obtained by a simple extractive work-up in up to 72% isolated yield, thus suggesting the potential practical usefulness of this procedure as a green alternative to the classical Schenk procedure in volatile organic solvents for the synthesis of tertiary alcohols. The chirality of the HBD, bearing an interesting basic primary amino group, is an intriguing feature currently under investigation for further exploitation. Full article

Aromatic heterocycles can be found in many molecules endowed with specific properties, in particular for applications in the fields of medicinal chemistry and materials science. In this group, we notably develop synthetic methodologies to selectively introduce iodine onto aromatic compounds and to use this heavy halogen in order to build heterocycles of interest. While we sometimes employed direct iodinations on electron-enriched aromatic compounds, we mainly optimized deprotometallation–iodolysis sequences to functionalize substrates sensitive to nucleophilic attacks. In particular, hindered lithium amide–metal trap tandems have been designed to overcome the low tolerance of some functional groups (e.g., ketones or sensitive diazines) toward organolithiums. The aromatic iodides generated in these ways have been involved in transition metal–catalyzed cross-couplings to access original scaffolds (oxazoloquinoxalines, pyrazinoisatins, pyrazinocarbazoles, etc.). We specifically developed the use of aromatic iodides in the copper-mediated N-arylation of anilines, e.g., to reach triarylamines. Combined with subsequent cyclizations, these reactions allowed access to numerous heterocyclic compounds (such as acridones, acridines, other aza-aromatic polycycles and helicene-like structures) with potential applications. From some of the scaffolds obtained, biological evaluation in the frame of collaborations allowed properties of interest to be discovered (e.g., specific inhibition of protein kinases GSK-3 or PIM, related to cancer development). Full article

In this work it is demonstrated that enantiomerically enriched N-alkyl 2-oxazolinylazetidines undergo exclusive α-lithiation, and that the resulting lithiated intermediate is chemically stable but configurationally labile under the given experimental conditions that afford enantioenriched N-alkyl-2,2-disubstituted azetidines. Although this study reveals the configurational instability of the diastereomeric lithiated azetidines, it points out an interesting stereoconvergence of such lithiated intermediates towards the thermodynamically stable species, making the overall process highly stereoselective (er > 95:5, dr > 85:15) after trapping with electrophiles. This peculiar behavior has been rationalized by considering the dynamics at the azetidine nitrogen atom, the inversion at the C-Li center supported by in situ FT-IR experiments, and DFT calculations that suggested the presence of η³-coordinated species for diastereomeric lithiated azetidines. The described situation contrasted with the demonstrated stability of the smaller lithiated aziridine analogue. The capability of oxazolinylazetidines to undergo different reaction patterns with organolithium bases supports the model termed “dynamic control of reactivity” of relevance in organolithium chemistry. It has been demonstrated that only 2,2-substituted oxazolinylazetidines with suitable stereochemical requirements could undergo C=N addition of organolithiums in non-coordinating solvents, leading to useful precursors of chiral (er > 95:5) ketoazetidines. Full article

The new complexes [Rh(Me)(trop₃P)] (2) and [Rh(Ph)(trop₃P)] (3) (trop = 5H-dibenzo[a,d]cyclohepten-5-yl) were synthesised by addition of organolithium reagents (MeLi and PhLi) to the parent pentacoordinated chloride complex [RhCl(trop₃P)]. The compounds have a trigonal bipyramidal structure with olefin-only ligands in the equatorial position and the methyl or phenyl substituent in the axial position. Oxidation of complexes 2 and 3 leads to the liberation of methyl and phenyl radicals, which were indirectly detected by reaction with common spin trapping reagents. Full article

N,N-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective to amide carbonyl at a low (−78 °C) temperature. These ketones, in reaction with organolithium reagents, give symmetrical and unsymmetrical aziridinyl carbinols. The usage of excess phenyllithium may serve as a special N-Boc-protecting group cleavage method for acid-sensitive substrates. Full article

The addition of functionalized organolithium compounds derived from 5-chloro-2-methoxy-1-pentene and 6-chloro-2-methoxy-1-hexene to N-tert-butanesulfinyl aldimines imines, and a subsequent hydrolysis of the enol ether moiety, yielded different δ- and ε-amino ketone derivatives, respectively, in moderate yields and diastereoselectivities. The application of these compounds in organic synthesis was demonstrated by the preparation of 2-substituted 6-methylpiperidines in a stereoselective manner, among them natural alkaloids (+)- and (−)-isosolenopsin A. Full article

The simple and efficient method was developed for the one-pot synthesis of B-substituted aryl derivatives of ortho-carborane with functional groups sensitive to organolithium and organomagnesium reagents using 9-iodo-ortho-carborane and generated in situ organozinc compounds. The method proposed was used to prepare a series of 9-aryl-ortho-carboranes, including those containing nitrile and ester groups, 9-RC₆H₄-1,2-C₂B₁₀H₁₁ (R = p-Me, p-NMe₂, p-OCH₂OMe, o-OMe, p-OMe, o-CN, p-CN, o-COOEt, m-COOEt, and p-COOEt). It was demonstrated that the same approach can be used for synthesis of diaryl derivatives of ortho-carborane 9,12-(RC₆H₄)₂-1,2-C₂B₁₀H₁₀ (R = H, p-Me). The solid-state structures of 9-RC₆H₄-1,2-C₂B₁₀H₁₁ (R = p-NMe₂, p-OCH₂OMe, o-OMe, o-CN, p-CN, m-COOEt, and p-COOEt) and 9,12-(p-MeC₆H₄)₂-1,2-C₂B₁₀H₁₀ were determined by single crystal X-ray diffraction. Full article