Addition Of Organolithiums Research Articles

An approach to hyperolactone C and analogues using late stage conjugate addition on an oxonium ylide-derived spirofuranone

A stereocontrolled synthesis of norphenyl hyperolactone C together with its utility as a direct precursor to the anti-HIV agent hyperolactone C and analogues by addition of organolithiums, are described. Preliminary studies to access this key building block in a catalytic enantioselective manner are also reported.

Very Simple One-Step Synthesis of Vinylphosphonates and Enamine Phosphonates by Direct Addition of Organolithium Reagents to 1-Alkynylphosphonates

Direct addition of organolithium to 1-alkynylphosphonates (1) afforded vinylphosphonates and enamine phosphonates (2) in good to excellent yields. The reaction was carried out in dry THF at low temperature and proved to be completely stereoselective (syn addition). Alkyl, aryl, and haloalkyl groups were attached to the alkynyl entity, so the resulting vinylphosphonates contained various functional groups. The stereochemistry of the products as well as mechanism of the reaction were determined based on 1H and 13C NMR. The synthesis of enamine phosphonates in the absence of complicated, highly expensive organometallic catalysis has not been previously reported.

Thioamides and Thioformamides for Sequential Reactions with Organolithium and Grignard Reagents

Abstract Sequential reactions of thioamides and thioformamides with organolithium and Grignard reagents are described. Thioiminium salts derived from these sulfur isologues of amides readily react with lithium acetylides to lead to several types of products, including α,β-unsaturated ketones, whereas sequential additions of lithium acetylides and Grignard reagents afford propargylamines. The direct addition of organolithium and Grignard reagents to thioformamides proceeds with high efficiency to give a range of tertiary amines.

Pyridine‐Directed Organolithium Addition to an Enol Ether

AbstractA previously reported anionic rearrangement of benzyl 2‐pyridyl ethers can now be accessed by a distinct and unusual mechanism: addition of alkyllithium reagents to α‐(2‐pyridyloxy)‐styrene triggers an anionic rearrangement to afford tertiary pyridyl carbinols. The process is explained by invoking a contra‐electronic, pyridine‐directed carbolithiation of the enol ether π‐system.

ChemInform Abstract: Single Electron Transfer in the Addition of Chiral Dipole-Stabilized Organolithiums to Carbonyls. Stereochemistry of a Chiral Nucleophile as a Mechanistic Probe.

Abstract Spectroscopic and stereochemical evidence is provided which suggests that single electron transfer (SET) accounts for the difference in selectivity observed in the reaction of metalated pivalamides and oxazolines with carbonyls.

ChemInform Abstract: Boron Trifluoride-Promoted Addition of Organolithiums to Oxime Ethers. A Facile Synthesis of Substituted Hydroxylamines.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis and Conjugate Additions to E-γ-Alkoxy-α- Substituted α,β-Unsaturated Sulfones.

Abstract (E)-γ-hydroxy-α,β-unsaturated sulfones have been readily functionalized at α-position via protection of hydroxyl group, metalation with n-BuLi and subsequent reaction with electrophiles. The conjugate addition of organolithiums to (E)-γ-methoxymethoxy-α-trimethylsilyl-α,β-unsaturated phenyl sulfones in Et 2 O is highly syn-stereoselective.

ChemInform Abstract: N-tert-Butyldimethylsilyl Imines as Intermediates for the Synthesis of Amines and Ketones.

Abstract Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-TBS ketimines, which were investigated as intermediaries for the synthesis of primary amines and ketones. N-silylimines were easily obtained by an organolithium addition to benzonitrile followed by a reaction with TBSCl in CH2Cl2. In situ reduction of these imines by BH3 and 1,3,2-oxazaborolidines 1 or 2 as chiral templates afforded the corresponding amines with modest to good enantiomeric excess.

ChemInform Abstract: Organolithium Addition to Styrene and Styrene Derivatives: Scope and Limitations.

Styrene and a range of aryl-substituted styrene derivatives are shown to undergo efficient carbolithiation–trapping reactions in diethyl ether at −78 to −25 °C. The reactivities of different types of organolithium reagents were found to be: tertiary, secondary > primary; ≫ alkenyl, methyl, phenyl. Electron donating groups (e.g. methoxy and dialkylamino) at the ortho- or para- positions of the benzene ring deactivate the double bond towards organolithium addition, but their reactions with butyllithium can be facilitated by using TMEDA as co-solvent. 2-Benzyloxystyrene and 2-allyloxystyrene undergo efficient carbolithiation at −78 °C, but at room temperature alkyl transfer occurs, generating the corresponding alkylated phenol. 2-Vinylnaphthalene also undergoes carbolithiation–carboxylation in reasonable yield.

ChemInform Abstract: Fluorine-Containing Butanolides and Butenolides. Vinylic Fluorine Displacement in 4,4-Dialkyl-2,3-difluoro-2-buten-4-olides and a Novel Rearrangement Induced by Organolithium Addition to a Carbonyl Group.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Low-Temperature Addition of Organolithiums to Functionalized Vinylsilanes under Formation of Secondary α-Lithiated Alkylsilanes

At -78 degrees C and in apolar solvents, the presence and quality of a coordinating side arm in vinylsilanes dictates both their reactivity toward alkyllithiums and the structural motif in the solid state, deciding whether a defined carbolithiation, slow polymerization or no reaction at all occurs. The crystal structures of the carbolithiation products of two vinylsilanes and methyllithium are presented, and the energetic barriers of the addition step with different alkyllithiums are investigated.

A convenient synthesis of 2-substituted indoles by the reaction of 2-(chloromethyl)phenyl isocyanides with organolithiums

The reaction of 2-(chloromethyl)phenyl isocyanides, readily available by dehydration of the respective N-[2-(chloromethyl)phenyl]formamides, with organolithiums produced 2-substituted indoles in satisfactory yields through addition of organolithiums to the isocyano carbon followed by intramolecular substitution reaction of the resulting imidoyl anion intermediates.

Stereoselective Synthesis of α-Arylalkylamines by Glycosylation-induced Asymmetric Addition of Organometallic Compounds to Imines

Activation of imines of aromatic aldehydes by N-glycosylation with O-pivaloyl-galactopyranosyl bromide (pivalobromogalactose) and subsequent addition of organotin, organolithium, Grignard, or organozinc reagents afforded α-arylalkylamines with moderate to high diastereoselectivity.

Gold Catalysis and Chiral Sulfoxides: Enantioselective Synthesis of Dihydroisoindol‐4‐ols

AbstractFurfurals and enantomerically pure sulfinamides have been condensed to N‐sulfinylimines. Addition of organolithium or ‐magnesium compounds to these imines allowed a 1,2‐induction. After propargylation, the sulfinamides gave low conversion with gold catalysts. Oxidation to chiral sulfonamides, propargylation and gold‐catalysed cycloisomerization to the phenol delivered non‐racemic dihydroisoindol‐4‐ols in good yields. In situ NMR studies prove the intermediacy of the arene oxide even with the AuCl3 catalyst.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Reactivity of the Triple Ion and Separated Ion Pair of Tris(trimethylsilyl)methyllithium with Aldehydes: A RINMR Study

Low-temperature rapid-injection NMR (RINMR) experiments were performed on tris(trimethylsilyl)methyllithium. In THF/Me2O solutions, the separated ion (1S) reacted faster than can be measured at -130 degrees C with MeI and substituted benzaldehydes (k >/= 2 s -1), whereas the contact ion (1C) dissociated to 1S before reacting. Unexpectedly, the triple ion reacted faster with electron-rich benzaldehydes relative to electron-deficient ones. The addition of HMPA had no effect on the rate of reaction of the triple ion with p-diethylaminobenzaldehyde, and the immediate product of the reaction was the HMPA-solvated separated ion 1S, with the Peterson product forming only slowly. Thus, the aldehyde is catalyzing the dissociation of the triple ion. HMPA greatly decelerated the reaction of 1S (<10 -10), providing an estimate of the Lewis acid activating effect of a THF-solvated lithium cation in an organolithium addition to an aldehyde.

Preferred Functionalization of Metallic and Small‐Diameter Single‐Walled Carbon Nanotubes by Nucleophilic Addition of Organolithium and ‐Magnesium Compounds Followed by Reoxidation

Covalent sidewall addition to single-walled nanotubes (SWNTs) of a series of organolithium and organomagnesium compounds (nBuLi, tBuLi, EtLi, nHexLi, nBuMgCl, tBuMgCl) followed by reoxidation is reported. The functionalized R(n)-SWNTs were characterized by Raman and NIR emission spectroscopy. The reaction of SWNTs with organolithium and magnesium compounds exhibits pronounced selectivity: in general, metallic tubes are more reactive than semiconducting ones. The reactivity of SWNTs toward the addition of organometallic compounds is inversely proportional to the diameter of the tubes. This was determined simultaneously and independently for both metallic and semiconducting SWNTs. The reactivity also depends on the steric demands of the addend. Binding of the bulky t-butyl addend is less favorable than addition of primary alkyl groups. Significantly, although tBuLi is less reactive than, for example, nBuLi, it is less selective toward the preferred reaction with metallic tubes. This unexpected behavior is explained by fast electron transfer to the metallic SWNTs having low-lying electronic states close to the Fermi level, a competitive initial process. The NIR emission of weakly functionalized semiconducting SWNTs, also reported for the first time, implies interesting applications of functionalized tubes as novel fluorescent reporter molecules.

Stereoselective conjugate addition of organolithium reagents to unprotected 4-hydroxy-2-cyclopentenones

The stereoselective conjugate addition reaction of organolithium reagents to unprotected 4hydroxycyclopentenones is reported. The OH group on the substrate is transformed into the corresponding magnesium alkoxide, which has been used to control the regioselectivity of the organolithium addition. Following this procedure, the conjugate addition reaction was obtained instead of the products of direct addition to the carbonyl group usually found in other organolithium additions to similar starting materials. Additionally, the OH group controls the cisstereochemistry of the final products. Both aspects, regioand stereoselectivity, can be understood by means of a chelation-controlled addition.

Regioselectivity, scope, and limitations of the addition of organolithium and allylmagnesium reagents to 1 H-pyridine-2-thiones; access to 3,4-, 3,6-, and 5,6-dihydropyridine-2-thiones

Organolithium and lithium allyldibutylmagnesate reagents add to readily available NH, NMe, NBn, and NPh substituted pyridine-2-thiones yielding 4- and/or 6-substituted 3,4- or 3,6-dihydropyridine-2-thiones, respectively. The regioselectivity of the addition is dependent on the solvent, temperature, substituent at the nitrogen, and the type or organometallic reactant used, and allows tailoring of both systems. A simple conversion of 6-substituted β,γ-unsaturated δ-thiolactams into their α,β-unsaturated isomers makes the above processes a highly versatile synthetic methodology to access 6-substituted 5,6-dihydropyridine-2-thiones—valuable Michael acceptors.

Preparation of Substituted Hydroquinones and Benzofurans from 1,4‐Quinone Monoketals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Diastereoselective Addition of Organolithium to Ferrocene-Carboxaldehyde Imines Derived from (R)- and (S)-1-Phenylethylamine: The Effect of External Additives

An efficient and flexible asymmetric synthesis of chiral ferrocenylamines 3a-c via diastereoselective addition of organolithium compounds to chiral imines is described. High diastereoselectivity(93% de) was observed with ferrocenecarboxaldehyde imine 2b in the presence of the Lewis acids BF3oOEt2. Keywords: Ferrocene, optically active amines, ferrocenecarboxaldehyde imine, asymmetric addition, organolithium, compounds, chiral synthesis