Alkynyl Lithium Research Articles

Synthesis and Photophysical Properties of Charge-Transfer-Based Pyrimidine-Derived α-Amino Acids.

The four-step synthesis of fluorescent pyrimidine-derived α-amino acids from an l-aspartic acid derivative is described. The key synthetic steps involved preparation of ynone intermediates via the reaction of alkynyl lithium salts with a Weinreb amide, followed by an ytterbium-catalyzed heterocyclization reaction with amidines. Variation of substituents at the C2- and C4-position of the pyrimidine ring allowed tuning of the photoluminescent properties of the α-amino acids. This revealed that a combination of highly conjugated or electron-rich aryl substituents with the π-deficient pyrimidine motif resulted in fluorophores with the highest quantum yields and overall brightness. Further analysis of the most fluorogenic α-amino acid demonstrated solvatochromism and sensitivity to pH.

Stereoselective synthesis of functionalized allenes from tartaric acid

Desymmetrization of the C 2 -symmetric bis -dimethylamide derived from tartaric acid by controlled addition of alkynyl lithium reagents furnished the mono alkynyl ketones which on reduction produced the corresponding propargyl alcohols with good diastereoselectivity. The propargyl alcohols were transformed to allenes using Claisen rearrangement. The formed allenes serve as a precursor for the synthesis of one of the THP units of the natural product sorangicin and for the synthesis of the polyhydroxy unit present in natural product anamarine. • Alkynyl ketones derived from tartaric acid were reduced to yield the corresponding propargyl alcohols with good selectivity (up to dr 90:10). • The propargyl alcohols were transformed to the allenes using microwave mediated Claisen rearrangement. • A masked tetrol and a functionalized tetrahydropyran were prepared using AuCl 3 catalyzed reaction.

Synthesis of allenylzinc reagents by 1,2-rearrangement of alkynyl(disilyl)zincates derived from acetylenic epoxides and acetylenic aziridines

Abstract Lithium alkynyl(disilyl)zincates obtained from metalated ethynyloxiranes, as well as from N - tert -butanesulfinyl(ethynyl)aziridines or N - tert -butanesulfonyl(ethynyl)aziridines, undergo 1,2-migration of the organosilyl group with ring opening of the oxirane or aziridine ring by S N i displacement. A developed protocol that involves n BuLi for the metalation step offers a straightforward approach to the corresponding δ-oxy- and δ-amino α-silyl allenylzinc intermediates. The reagents derived from the epoxides are amenable to subsequent in situ condensation with aldehydes or ketones to provide 1,3-diols but not those derived from aziridines that only react sluggishly in similar condensations.

Synthesis and Structural Characterization of a Lithium Alkynyl(hydrazinediido)zirconate and its Protonolysis to an Alkynylhydrazido(1–)zirconium Complex

AbstractReaction of the hydrazinediido complex 1 with lithiated phenylacetylene selectively gave the lithium alkynyl(hydrazinediido)zirconate [(N2TBSNpy)Zr{μ‐NNPh2‐1κN:2κN}{μ‐PhCC‐1κC:2κC}‐Li(py)] (2), which reacted with one molar equivalent of TMEDA to give the corresponding Li‐TMEDA derivative [(N2TBSNpy)Zr{μ‐NNPh2‐1κN:2κN}{μ‐PhCC‐1κC:2κC}‐Li(TMEDA)] (3). The details of the molecular structure of complex 3 were established by single‐crystal X‐ray structure analysis. The lithium hydrazinediidozirconate 2 was treated with triethylammonium hydrochloride yielding the corresponding alkinylzirconium hydrazido(1‐) complex 4 as a mixture of two diastereomers.

Scalable synthesis of the pink gypsy moth Lymantria mathura sex pheromone (–)-mathuralure

Mathuralure (1) is the major sex pheromone component of the pink gypsy moth Lymantria mathura, a potentially devastating invasive species to North America. To support population monitoring of this moth, a gram-scale synthesis of (–)-mathuralure (1) was developed. This process relies on coupling an alkynyl lithium species with a chloroepoxide and provides access to the natural product in a 10% yield over 10 steps.

Reactivity of the ester group attached isoxazoline, benzisoxazole, and isoxazole: a facial preparation of 3-acyl-substituted these heterocycles

A facile preparation of 3-acyl-substituted isoxazolines, benzisoxazoles, and isoxazoles from the corresponding 3-carboxylate esters is described. The process, involving reaction of the ester derivative of 3-carboxylic acid substituted heterocycles with Grignard or alkynyl lithium reagents, leads to direct generation of the corresponding 3-acyl heterocycle. The presence of α-imino ester moieties in the heterocyclic substrates for the reactions is thought to be a key feature governing the nature of these transformations. The synthetic utility of the new methodology is demonstrated by its application in a two-step route for the preparation of novel linked bis-heterocycles.

A one‐pot synthesis of alkynyl sulfides from terminal alkynes

AbstractA one‐pot synthesis of alkynyl sulfide from terminal alkyne has been reported via lithiation of the alkyne, oxidative addition of sulfur, consecutively followed by the nucleophilic substitution of lithium alkynyl thiolate to various halides. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:105–110, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20745

ChemInform Abstract: Recent Advances in Selective Organic Synthesis Mediated by Transition Metal Complexes

This short review covers some useful synthetic transformations mediated by group 6 Fischer alkoxy carbene complexes. Alkenyl carbene complexes derived from (±)-8-phenylmenthol are suitable Michael acceptors towards organolithium reagents -alkyllithium and lithium enolate derivatives-yielding ultimately b-alkyl substituted aldehydes with 80±98% enantiomeric excess. The reaction of (menthyloxy)aryl carbene complexes with sBuLi and tBuLi resulted in clean dearomatization leading to 1,4-cyclohexadiene derivatives. If alkynyl lithium, instead of alkyllithium, compounds are reacted with aryl carbene complexes different products -furans, propargyl ethers, alkoxyindenes are selectively produced. Enamines derived from (S)-methoxymethylpyrrolidine and both aldehydes and ketones react with alkenyl carbenes to afford with very high selectivity [3‡2] cycloadducts which are elaborated into useful, enantiopure 3,4-disubstituted cyclopentanones and 2,3-disubstituted 2-cyclopentenones, respectively. The [4‡3] carbocyclization occurs from alkenyl carbene complexes and 2-aminobutadiene derivatives, while the analogous heterocyclization can be accomplished from various types of azabutadienes and both alkenyl and alkynyl derivatives. Ef®cient structural modi®cations of terpenes can be done using boroxycarbene complexes via C±H insertion reactions. Finally, representative examples of cyclopropanation of electronically neutral alkenes with Fischer carbene complexes are provided.

ChemInform Abstract: Chemoselective Addition of in situ Prepared Lithium Alkynyl Borates to Aldehydes: A Practical and Transition Metal‐Free Approach Toward the Synthesis of Propargylic Alcohols.

AbstractChemInform 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.

Alkyne-Protected Ruthenium Nanoparticles

Stable ruthenium nanoparticles protected by 1-octynyl fragments were synthesized by a wet chemical method. Transmission electron microscopic measurements showed that the resulting particles exhibited an average core diameter of 2.55 ± 0.15 nm with well-defined Ru crystalline lattice fringes. Because of the formation of Ru—C≡ bonds, the C≡C vibrational stretch was found in FTIR measurements to red-shift to 1936 cm−1 from 2119 cm−1 that was observed for monomeric 1-octyne. Interestingly, the nanoparticles underwent ligand exchange reactions with alkynyl lithium (e.g., 5-phenyl-1-pentynyl lithium) for further surface functionalization, as manifested in FTIR as well as 1H and 13C NMR measurements. Optically, whereas UV−vis absorption measurements exhibited only a featureless profile, the Ru nanoparticles displayed apparent photoluminescence with an emission peak at 428 nm, which was accounted for by intraparticle charge delocalization as a consequence of the strong Ru—C≡ bonds and the conducting Ru metal cores such that the particle bound C≡C moieties behaved analogously to diacetylene derivatives. The impacts of the interfacial bonding interactions on intraparticle charge delocalization were further illustrated by Ru nanoparticles functionalized with a mixed monolayer of both octyne and ethynylferrocene ligands. At a ferrocene surface coverage of ca. 13%, electrochemical measurements depicted two pairs of voltammetric peaks with a potential spacing of 265 mV. A new NIR absorption band centered around 1687 nm also started to emerge with the addition of nitrosonium tetrafluoroborate (NOBF4) as the oxidizing reagent and the peak intensity exhibited a volcano-shape dependence on the amount of NOBF4 added. These observations strongly suggested that there existed effective intervalence charge transfer between the particle-bound ferrocene groups at mixed valence, analogous to the observation where the ferrocene moieties were bound onto the particle surface by Ru—carbene π bonds.

Chemoselective addition of in situ prepared lithium alkynyl borates to aldehydes: a practical and transition metal free approach toward the synthesis of propargylic alcohols

Abstract A convenient synthesis of functionalized propargylic alcohols arising from the 1,2-addition of lithium alkynyl-trimethyl borate onto aldehydes under transition metal free mild conditions is reported. The reaction tolerates a wide range of functional groups, is highly chemoselective and the propargylic alcohols are isolated in good to excellent yields.

Synthesis and Characterization of Alkynyl Complexes of Groups 1 and 2

The synthesis of N-heterocyclic carbene adducts of alkynyl lithium and magnesium is achieved, and different degrees of association are observed. Reaction of strontium amide nacnacSrN(SiMe(3))(2)(thf) (nacnac = CH(CMe2,6-iPr(2)C(6)H(3)N)(2)) with PhC[triple bond]CH in THF yields the dimeric alkynyl complex [nacnacSr(thf)(mu-C[triple bond]CPh)](2) which shows an interesting coordination geometry around the metal center. The compound retains the THF molecules, unlike its lighter congener, even in hydrocarbon solvents.

ChemInform Abstract: Copper(I)‐Mediated Oxidative Cross‐Coupling Between Functionalized Alkynyl Lithium and Aryl Magnesium Reagents.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Copper(I)‐Mediated Oxidative Cross‐Coupling between Functionalized Alkynyl Lithium and Aryl Magnesium Reagents

Copper(I)‐Mediated Oxidative Cross‐Coupling between Functionalized Alkynyl Lithium and Aryl Magnesium Reagents

Ring Opening Reaction of Epoxides under Aryl Acetylene/ZnBr2/DIEA Conditions

Recently, we have reported the usefulness of ZnBr2/DIEA (N,N-diisopropylethylamine) combination for the in situ generation of zinc acetylide species from terminal acetylenic compounds. We applied the system to the reactions with Ntosylimines, activated quinolinium salts, and carboxylic acid chlorides. The alkynylation of epoxide via ring opening with metal acetylide is an important carbon-carbon bond forming reaction. However, this useful reaction suffers from some intrinsic limitations including low yields and regioselectivity. Recently, several new methods have been suggested in order to solve these problems. Lithium acetylide in the presence of BF3 etherate 3a or Et2AlCl, 3b,3c titanium acetylides, trimethylgallium-catalyzed lithium acetylide in the presence of LiClO4 3f all afford better yields than the classical methods. The ring opening reaction of epoxide with these reagent combinations proceeded at the least hindered position without a special substituent which control the approach of the metal acetylide by chelation with the special substituent. Recently, regioselective ring opening of epoxide with lithium alkynyl trimethylaluminium ate complex in the presence of BF3 etherate was reported. 4c In these respects, we decided to examine the feasibility of the alkynylation of epoxide with ZnBr2/DIEA system. 1

Synthesis, charge distribution, and dimerization behavior of lithium alkynylselenolates

AbstractThe reactivity of alkynyl lithium compounds toward elemental gray selenium yields alkynylselenolates, which show significant interaction with the lithium counter ions, depending on solvent polarity and the electronic nature of the adjacent organic substituent. Likewise the dimerization behavior is different for alkyl‐ and aryl‐substituted alkynylselenolates. From the latter, unsymmetrical 1,3‐selenol is formed, the molecular structure of which was confirmed by X‐ray structure analysis. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:169–222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20088

에틸 2-피리딜 옥살레이트를 이용한 α-케토 에스터의 간편한 합성

α-Keto esters have attracted interest as precursors of α-keto acids, which play important roles in the biosynthesis of amino acids and enzyme inhibitors. The general methods for the synthesis of α-keto esters involve direct coupling between Grignard or organolithium reagents and derivatives of oxalic esters. The reaction of triethoxyacetonitrile with organolithium reagents leads to the formation of α-keto esters after acidic hydrolysis, but Grignard reagents provide esters. The treatment of alkyl α-oxo-1H-imidazole-1-acetates or diethyl oxalate with Grignard reagents affords the corresponding α-keto esters in mild conditions. However, these imidazolides gave low yields when alkyl Grignard reagents were used and the reaction of diethyl oxalate with Grignard reagents required excess oxalate. The preparation of α-oxo alkynoates was successful by the reaction of monoethyloxalic acidN-methoxy-N-methylamide and alkynyl lithium reagents, but the corresponding reaction was fruitless when diethyl oxalate or ethyl α-oxo-1H-imidazole-1-acetate was used. The cross-coupling reaction of methyl oxalyl chloride with organocopper reagents and the addition of Grignard reagents to 1-[N(alkoxyoxalyl) -N-methylamino]-3-methylimidazolium iodides produce the corresponding α-keto esters, but the separation of products is often tedious and the availability of these imidazolium salts is limited. It has also been reported that oxidation of dimethyl hydrazone, ozonolysis of methyl acrylate/ reduction with Ph3P 10 or ethyl 3-hydroxy acrylate derivatives, and oxidative cleavage of cyanoketophosphoranes/subsequent trapping with alcohol could produce α-keto esters, but these routes require for multi-step. In this paper we wish to report that α-keto esters can be conveniently prepared by the treatment of ethyl 2-pyridyl oxalate with Grignard reagents in a one-step.

Stereospecific and Efficient Alkynylation at the More Hindered Carbon of Trisubstituted Epoxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereospecific and efficient alkynylation at the more hindered carbon of trisubstituted epoxides.

The stereospecific and regioselective C(3) alkynylation of trisubstituted epoxides has been achieved with lithium alkynyl trimethylaluminium ate complexes in the presence of BF3 x OEt2.

Efficient coupling reactions of lithium alkynyl(triisopropoxy)borates with aryl halides: application to the antifungal terbinafine synthesis

Thermally stable lithium alkynyl(triisopropoxy)borates were reacted with several aryl halides in the presence of palladium catalysts to give the corresponding cross-coupling products in excellent yields. The present methodology has been successfully applied to the antifungal terbinafine synthesis.