Search Results (13)

While organolithium reactions hold great promise in synthetic chemistry, their high reactivity, strong exothermicity, and the instability of intermediates often limit their application, making the effective control of reaction processes difficult in traditional batch reactors. This review systematically summarizes the latest advances in utilizing flow chemistry technology to address process challenges related to organolithium reactions from 2014 to 2025. From a process perspective, we systematically discuss the literature cases regarding three key themes: the synthesis of organic compounds applied in the pharmaceutical field, the development of novel methods centered on effective process control (reaction temperature, residence time, phase state, multi-step reaction sequence, and safety), and fundamental process research on continuous flow organolithium reactions. Analysis shows that continuous flow systems provide a powerful platform for fully realizing the potential of organolithium chemistry by enhancing heat/mass transfer and precisely controlling reaction parameters. This review emphasizes how flow chemistry technology not only improves process safety and efficiency but also enables transformations and process scaling that are difficult or impossible in batch modes, thus providing a novel process intensification method for modern synthetic chemistry. 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

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

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

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

This mini-review summarizes the syntheses and functionalizations of dithieno[1,4]thiazines and bis[1]benzothieno[1,4]thiazines, both electron density-enriched congeners of phenothiazines with remarkable electronic properties. Diversity-oriented, straightforward, and efficient syntheses, including versatile one-pot processes, have been developed for the anellated 1,4-thiazines as well as various functionalization for the expansion of the π-systems. Thereby, syntheses of different regioisomers depending on the (benzo)thieno-thiazine anellation are discussed, which exert a deep impact on the electronic properties. The tunable photophysical and electrochemical properties of dithieno[1,4]thiazines and bis[1]benzothieno[1,4]thiazines outscore phenothiazines on many points and promise an enormous potential in molecular electronics and applications beyond. Full article

Polyolefins (POs) are the most abundant polymers. However, synthesis of PO-based block copolymers has only rarely been achieved. We aimed to synthesize various PO-based block copolymers by coordinative chain transfer polymerization (CCTP) followed by anionic polymerization in one-pot via conversion of the CCTP product (polyolefinyl)₂Zn to polyolefinyl-Li. The addition of 2 equiv t-BuLi to (1-octyl)₂Zn (a model compound of (polyolefinyl)₂Zn) and selective removal or decomposition of (tBu)₂Zn by evacuation or heating at 130 °C afforded 1-octyl-Li. Attempts to convert (polyolefinyl)₂Zn to polyolefinyl-Li were unsuccessful. However, polystyrene (PS) chains were efficiently grown from (polyolefinyl)₂Zn; the addition of styrene monomers after treatment with t-BuLi and pentamethyldiethylenetriamine (PMDTA) in the presence of residual olefin monomers afforded PO-block-PSs. Organolithium species that might be generated in the pot of t-BuLi, PMDTA, and olefin monomers, i.e., [Me₂NCH₂CH₂N(Me)CH₂CH₂N(Me)CH₂Li, Me₂NCH₂CH₂N(Me)Li·(PMDTA), pentylallyl-Li⋅(PMDTA)], as well as PhLi⋅(PMDTA), were screened as initiators to grow PS chains from (1-hexyl)₂Zn, as well as from (polyolefinyl)₂Zn. Pentylallyl-Li⋅(PMDTA) was the best initiator. The M_n values increased substantially after the styrene polymerization with some generation of homo-PSs (27–29%). The M_n values of the extracted homo-PS suggested that PS chains were grown mainly from polyolefinyl groups in [(polyolefinyl)₂(pentylallyl)Zn]⁻[Li⋅(PMDTA)]⁺ formed by pentylallyl-Li⋅(PMDTA) acting onto (polyolefinyl)₂Zn. Full article

Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research. Resistance of a nitroxide group bearing an unpaired electron to chemical reduction with low-molecular-weight antioxidants and enzymatic systems is of critical importance for these applications. The redox properties of nitroxides are known to depend on the ring size (for cyclic nitroxides) and electronic and steric effects of the substituents. Here, two highly strained nitroxides, 5-(tert-butyl)-5-butyl-2,2-diethyl-3-hydroxypyrrolidin-1-oxyl (4) and 2-(tert-butyl)-2-butyl-5,5-diethyl-3,4-bis(hydroxymethyl)pyrrolidin-1-oxyl (5), were prepared via a reaction of the corresponding 2-tert-butyl-1-pyrroline 1-oxides with butyllithium. Thermal stability and kinetics of reduction of the new nitroxides by ascorbic acid were studied. Nitroxide 5 showed the highest resistance to reduction. Full article

The synthetic route for introduction of fluorophenylalkyl (compounds 5, 7, 14 and 15) and fluorophenylalkenyl (compounds 4E and 13) side chains at C-6 of the pyrimidine nucleus involved the lithiation of the pyrimidine derivatives 1, 2 and 11 and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with 2-fluorophenylacetone, 4-fluoroacetophenone or ethyl 4-fluorobenzoate as electrophiles. The structures of novel compounds were confirmed by ¹H-, ¹⁹F- and ¹³C-NMR and MS. Compounds 8 and 10 containing unsaturated fluorophenylalkyl side chains showed better inhibitory effect than their saturated fluorophenylalkylated pyrimidine counterparts 7 and 9. A conformational study based on NOE enhancements showed the importance of the double bond and substitution in the side chain for the conformational preferences in relation to inhibitory activity. Among all tested compounds, C-5 furyl (12) and phenyl (13 and 15) substituted pyrimidine derivatives showed significant cytostatic activities against all tested tumor cell lines. Full article