organolithium

We describe an organophotoredox-catalyzed sp3 C-S coupling of N -sulfinylamines with bench-stable alkyltrifluoroborates as a latent nucleophilic counterpart en route to alkylsulfinamides in high efficiency. In contrast to the two-electron reactivity of traditional organometallic reagents, this catalytic method reports the single-electron process of an organometallic reagent with N -sulfinylamines in C-S coupling. This mild and scalable protocol offers operational simplicity and exceptional functional group compatibility, including ketone, ester, amide, nitrile, and halides, that is vulnerable to organolithium or Grignard reagents...

The development of new molecules for the treatment of calmodulin related cardiovascular or neurodegenerative diseases is an interesting goal. In this work, we introduce a novel strategy with four main steps: (1) chemical synthesis of target molecules, (2) Förster Resonance Energy Transfer (FRET) biosensor development and in vitro biological assay of new derivatives, (3) Cheminformatics models development and in vivo activity prediction, and (4) Docking studies. This strategy is illustrated with a case study...

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)...

The synthesis of group 4 metal 1-metallacyclobuta-2,3-dienes as organometallic analogues of elusive 1,2-cyclobutadiene has so far been limited to SiMe3 substituted examples. We present the synthesis of two Ph substituted dilithiated ligand precursors for the preparation of four new 1-metallacyclobuta-2,3-dienes [rac-(ebthi)M] (M=Ti, Zr; ebthi=1,2-ethylene-1,10-bis(η5-tetrahydroindenyl)). The organolithium compounds [Li2(RC3Ph)] (1b: R = Ph, 1c: R = SiMe3) as well as the metallacycles of the general formula [rac-(ebthi)M(R1C3R2)] (2b: M=Ti, R1=R2=Ph, 2c: M=Ti, R1=Ph, R2=SiMe3; 3b: M=Zr, R1=R2=Ph; 3c: M=Zr, R1=Ph, R2=SiMe3) were fully characterised...

Linkage chemistry and functional molecules derived from the stereogenic sulfur(VI) centre have important applications in organic synthesis, bioconjugation, drug discovery, agrochemicals and polymeric materials. However, existing approaches for the preparation of optically active S(VI)-centred compounds heavily rely on synthetic chiral S(IV) pools, and the reported linkers of S(VI) lack stereocontrol. A modular assembly method, involving sequential ligand exchange at the S(VI) centre with precise control of enantioselectivity, is appealing but remains elusive...

A simple and effective organolithium approach to the synthesis of 2-substituted benzo[cd]indoles from peri-dihalonaphthalenes and nitriles has been developed. The reaction proceeds via a surprisingly easy intramolecular aromatic nucleophilic substitution facilitated by the "clothespin effect". The discovered transformation provides good isolated yields, allows usage of an extensive range of nitriles, and demonstrates a good substituents tolerance. UV-absorption and NMR spectra of the obtained benzo[cd]indoles and their protonated forms demonstrated exclusive protonation to indole nitrogen atom even in the presence of two NMe2 groups in positions 5 and 6 (i...

For the first time through quantum chemistry methods, the effective use of 1 J CLi spin-spin coupling constants as descriptors for assessing the formation of strained metallacycles is demonstrated. Both acyclic organolithiums and 3- to 7-membered metallacycles are examined. 80 organolithium compounds, including both monomeric and dimeric species, with ligands containing fluorine, nitrogen, oxygen, and carbon (in the form of carbanions), are tested. In general, the 1 J CLi values below 12 Hz for monomeric species and below 6 Hz for dimeric species serve as clear indicators of strained monomeric metallacycle formation (for 6 Li nuclei)...

A Cu-catalyzed asymmetric synthesis of silicon-stereogenic benzoxasiloles has been realized via intramolecular Si-O coupling of [2-(hydroxymethyl)phenyl]silanes. Cu(I)/difluorphos is found to be an efficient catalytic system for enantioselective Si-C bond cleavage and Si-O bond formation. In addition, kinetic resolution of racemic substituted [2-(hydroxymethyl)phenyl]silanes using Cu(I)/ PyrOx (pyridine-oxazoline ligands) as the catalytic system is developed to afford carbon- and silicon-stereogenic benzoxasiloles...

Non-covalent interactions such as coordination of an organolithium reagent by a directing group and steric repulsion of substituents strongly affect the halogen-lithium exchange process. Here we present the manifestation of the "buttressing effect" - an indirect interaction between two substituents issued by the presence of a third group - and its influence on the ease and selectivity of the bromine-lithium exchange and the reactivity of formed aryllithiums. The increase of the size of the "buttressing" substituent strongly affects the conformation of a NMe2 group, forcing it to hinder ortho-bromine and thus slowing down the exchange...

The bicyclic 1,2-substituted, 1,3-diene monomer nopadiene (1 R ,5 S )-2-ethenyl-6,6-dimethylbicyclo[3.1.1]hept-2-ene was successfully polymerized by anionic and catalytic polymerization. Nopadiene is produced either through a facile one-step synthesis from myrtenal via Wittig-olefination or via a scalable two-step reaction from nopol (10-hydroxymethylene-2-pinene). Both terpenoids originate from the renewable β-pinene. The living anionic polymerization of nopadiene in apolar and polar solvents at 25 °C using organolithium initiators resulted in homopolymers with well-controlled molar masses in the range of 5...

Herein, a visible-light-induced nickel-catalyzed cross-coupling of aryl bromide with nitrile has been reported. By utilization of readily available nitriles as carbonyl precursors, a range of structurally diverse aryl ketones were facilely constructed. The synthetic simplicity, mild reaction conditions, and acidic functional group tolerance would broaden the synthetic utilities of this developed protocol as an expedient alternative to Grignard/organolithium protocols.

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- i Pr3 -C6 H2 ) with trimethylsilyl azide afforded the silyltriazene TripN2 N(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...

A general and straightforward procedure for the lithiation / trapping of cyclic sulfides such as tetrahydrothiophene, tetrahydrothiopyran and a thiomorpholine is described. Trapping with a wide range of electrophiles is demonstrated, leading to more than 50 diverse α-substituted saturated sulfur heterocycles. The methodology provides access to a range of α-substituted cyclic sulfides that are not easily synthesised by the currently available methods.

Herein we report the utilization of N-heterocyclic nitrenium ions - easily prepared, bench-stable and non-oxidating nitrogen sources for the efficient electrophilic amination of aliphatic and aromatic organometallic nucleophiles, towards the facile and general preparation of primary amines. To this end, a plethora of abundant organolithium and organomagnesium reagents were combined with nitrenium salts to generate a variety of previously unexplored N -alkyl and N -aryl triazanes. Through the simple hydrogenolysis of these relatively stable triazanes, we have prepared a diverse scope of primary amines, including linear and branched aliphatic as well as (hetero)aromatic amines possessing various stereo-electronic substituents...

With their highly reactive respective C-Na and N-Na bonds, organosodium and sodium amide reagents could be viewed as obvious replacements or even superior reagents to the popular, widely utilised organolithiums. However, they have seen very limited applications in synthesis due mainly to poor solubility in common solvents and their limited stability. That notwithstanding in recent years there has been a surge of interest in bringing these sustainable metal reagents into the forefront of organometallics in synthesis...

Aryl amines are of constant interest in organic synthesis owing to their ubiquity in natural products, pharmaceuticals and organic materials. However, C-H amination or pre-functionalization frequently results in uncontrollable site selectivity, over activation and the generation of inseparable mixtures of regio-isomers. Here we present a novel metal free Dötz-type aminobenzannulation reaction that circumvents the selectivity issues inherent in aromatic chemistry, as well as the use of stoichiometric unstable organolithium reagents and toxic chromium complexes...

A family of commercially available organolithium compounds were found to effectively catalyze the heterodehydrocoupling of silanes and amines under ambient conditions. Ubiquitous n BuLi (1) was utilized as the benchmark catalyst, where an array of primary, secondary, and tertiary arylsilanes were coupled to electron-donating amines, affording aminosilanes in high conversions with short reaction times. Preliminary mechanistic analysis is consistent with a nucleophilic-type system that involves the formation of a hypervalent silicon intermediate...

The organometallic compounds of lithium ions have garnered continuous interest as indispensable precursors for the syntheses of organometallic complexes of main-group metals, transition metals, lanthanide metals, and actinide metals. In this work, we present a strategy for the preparation of a series of polynuclear lithium complexes. This methodology features the utilization of organolithium reagents both as metal sources to coordinate with the ligands and as nucleophilic reagents to undergo nucleophilic addition to the C═N bonds of the ligands...

A new method to access flavones in a convergent fashion has been developed, based on the Stork-Danheiser reaction. By this method, 4-methoxy coumarins are allowed to react with organolithium at low temperatures (-78 °C to -40 °C) and then acidic workup gives the desired flavones in 18-86% yields. This method features transition metal-free conditions, readily available starting materials, and simple operation. It is particularly efficient when rapid generation of B ring flavone derivatives is desired...

We have re-examined the reactivity of the manganese dinitrogen complex [Cp(CO)2Mn(N2)] (1, Cp = η5-cyclopentadienyl, C5H5) with phenylithium (PhLi). By combining experiment and density functional theory (DFT), we have found that, unlike previously reported, the direct nucleophilic attack of the carbanion onto coordinated dinitrogen does not occur. Instead, PhLi reacts with one of the CO ligand to provide an anionic acylcarbonyl dinitrogen metallate [Cp(CO)(N2)MnCOPh]Li (3) that is stable only below -40 °C...