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The continuous synthesis of organozinc reagents and their immediately following subsequent also continuous consumption in catalyzed and noncatalyzed coupling reactions were investigated. In the fir...

The continuous synthesis of organozinc reagents and their immediately following subsequent also continuous consumption in catalyzed and noncatalyzed coupling reactions were investigated. In the first step, a bed of Zn turnings at variable liquid throughputs and concentrations of organic halide solutions was used, and the formed Zn organometallics were analyzed for quality control. They were then directly pumped into a second step, namely, Reformatsky, Saytzeff, and Negishi coupling reactions. In the organozinc halides' formation, a novel process window was employed by using a large molar excess of Zn turnings and investigating mechanical as well as chemical Zn activation. Subsequent couplings of the freshly prepared Zn organometallics were done using examples of a Reformatsky, Saytzeff, and Negishi coupling reaction. For the Zn organometallics' formation, a laboratory-scale reactor setup previously built for Grignard reagent formation was evaluated including a Zn replenishing unit; the same reactor was also used in the metal-catalyzed subsequent step (Negishi coupling). The main objective of this work was to establish the scalable continuous formation of Zn organometallic reagents enabling fast and safe process optimization, analyze the reagents for their purity, and then immediately consume them in various follow-up steps, always only leaving a very small amount of reactive and sensitive organometallic reagent in the setup. It was found that full conversion of the employed halides could be achieved within a single passage through the reactor with organozinc yields of 82-92%, as well as being able to successfully perform subsequent non- and metal-catalyzed coupling steps with yields of up to 92%. A pilot-scale setup allowing a liquid throughput of up to 3-5 L/h has also been built and is ready to be tested with the synthesis as established here.

The Negishi cross-coupling reaction is the nickel- or palladium-catalyzed coupling of organozinc compounds with various halides or triflates (aryl, alkenyl, alkynyl, and acyl).

The TaCl 5 -mediated reaction between monosubstituted alkenes and Et 2 Zn affords 3-(R-substituted)-n-butylzincs in high yield (up to 92%) and regioselectivity. Organozinc reagents bearing a longer alkyl chain (R = Pr n , Bu n , Am n , Hex n, ) react with 1-alkenes in the presence of TaCl 5 as the catalyst to give two types of organozinc compound having iso -alkyl structure. The probable mechanism of the carbozincation reaction implies the formation of β-substituted and β,β'-disubstituted tantalacyclopentanes as the key intermediates. The thermodynamic probability of the mechanistic elementary stages for the ethylzincation of terminal alkenes has been estimated using DFT PBE/SBK method Keywords : Catalysis; Organozin с compounds; 1-Alkenes; Carbozincation; Tantalacyclopentanes; DFT calculations 1. Introduction ∗ Corresponding author. Tel./fax: +7 347 2842750. E-mail address: Sultanov55@mail.ru (R.M. Sultanov). Leave this area blank for abstract info. The tantalum-catalyzed carbozincation of 1-alkenes with zinc dialkyls

The reactions of ZnEt2 with NNN-tridentate pincer type pyrrolyl ligands, 2,5-bis((dimethylamino)methylene)-1H-pyrrole (HL1), 2,5-bis((pyrrolidin-1-yl)methylene)-1H-pyrrole (HL2) and 2,5-bis((piperidino)methylene)-1H-pyrrole (HL3), afford zinc ethyl compounds [C4H2N(2,5-CH2NMe2)2]ZnC2H5 (1), [C4H2N(2,5-CH2N(CH2)4)2]ZnC2H5 (2), and [C4H2N(2,5-CH2N(CH2)5)2]ZnC2H5 (3) in high yield. Subjecting 1, 2, 3 with one equivalent of tert-butylphenol in THF generated {[C4H2N(2,5-CH2NMe2)2]Zn(O–C6H4-4-tBu)}2 (4), {[C4H2N(2,5-CH2N(CH2)4)2]Zn(O–C6H4-4-tBu)}2 (5), {[C4H2N(2,5-CH2N(CH2)5)2]Zn(O–C6H4-4-tBu)}2 (6), respectively. Each has been characterized by satisfactory C, H and N microanalysis, NMR spectroscopy at ambient temperature, and single crystal X-ray structural analysis. The compounds Et6Zn6O2[C4H2N(2,5-CH2N(CH2)4)2]2 (7) and Et6Zn6O2[C4H2N(2,5-CH2N(CH2)5)2]2 (8) obtained accidentally from zinc ethyl compounds with traces of water. Each of compound 1–6 has been used as initiator for cyclotrimerization of isocyanate, and the organozinc compound 3 shows moderate reactivity toward the cyclotrimerization of isocyanate in Et2O solvent under mild conditions.

Pure rotational spectra of the 37ClZnCH3, ClZnCD3, and ClZn13CH3 isotopologues of monomeric ClZnCH3 ( X 1A1) have been recorded using millimeter-wave direct absorption techniques in the frequency range 263–303 GHz. These species were synthesized in the gas phase in a DC discharge by the reaction of zinc vapor, produced in a Broida-type oven, with 37ClCH3 (in natural chlorine abundance), ClCD3, or Cl13CH3. Five to eight rotational transitions J + 1 ← J consisting of K ladder structure were measured for each isotopologue, identifying all three species as prolate symmetric tops. The data for each isotopologue were analyzed with a symmetric top Hamiltonian and rotational and centrifugal constants determined. In combination with previous measurements of Cl64ZnCH3, Cl66ZnCH3, and Cl68ZnCH3, an rm(2) structure was determined for this organozinc compound. The bond lengths in ClZnCH3 were calculated to be rCl-Zn = 2.0831(1) A, rZn-C = 1.9085(1) A, and rC-H = 1.1806(5) A, considerably different from those established from crystal structures of related species ClZnCH2CH3 and ClZnEtTMEDA. The H C H bond angle was found to be 110.5° – slightly larger than that in methane. These data serve to benchmark future structure calculations of organozinc compounds, which are widely used in organic synthesis.

[Tris(2-pyridylthio)methyl]zinc fluoride, [κ(4)-Tptm]ZnF, the first example of an organozinc compound that features a terminal fluoride ligand, may be obtained by the reactions of either [Tptm]ZnX (X = H, OSiMe3) with Me3SnF or [κ(4)-Tptm]ZnI with [Bu(n)4N]F. Not only is the fluoride ligand of [κ(4)-Tptm]ZnF susceptible to coordination by B(C6F5)3 to give the adduct [κ(4)-Tptm]ZnFB(C6F5)3, but it is also an effective hydrogen bond and halogen bond acceptor. For example, X-ray diffraction studies demonstrate that [κ(4)-Tptm]ZnF forms an adduct with water in which hydrogen bonding between the fluoride ligands and water molecules serves to link pairs of [κ(4)-Tptm]ZnF molecules with a [F···(H-O-H)2···F] motif. Furthermore, (1)H and (19)F NMR spectroscopic studies provide evidence for hydrogen bonding and halogen bonding interactions with indole and C6F5I, respectively.

The syntheses and characterization of two organozinc compounds were accomplished by reacting phenalenyl (PLY)-based ligands with ZnMe2. Reactions of [HN(Cy),O-PLY] and [HN(Cy),N(Cy)-PLY] ligands with ZnMe2 led to the formation of the dimeric orange-colored organozinc compound [N(Cy),O-PLY-ZnMe]2 (1) and red-colored monomeric organozinc compound [N(Cy),N(Cy)-PLY-ZnMe] (2) under evolution of methane. Both 1 and 2 were characterized by NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction study. The organozinc compound 2 was tested as a catalyst for intramolecular hydroamination of both unactivated primary and secondary aminoalkenes in the presence of an externally added activator, which generated the zinc-based cation in situ. The catalytic result obtained from the present catalyst 2 was compared with the catalysts having similar structure from previous studies. The DFT calculation indicates that the stability of the in situ generated cation plays a significant role in the catalytic act...

Oxidative dissolution of zinc in the system of benzyl chloride-dimethylacetamide was investigated. The reaction stereochemistry as well as intermediates and reaction products formed were studied. The kinetic and thermodynamic parameters of the process were measured. The process was shown to follow the Langmuir-Hinshelwood mechanism with the formation of benzyl radicals and mono-solvated organozinc compound on the zinc surface. The components of mixture are adsorbed at various sites of the zinc surface, while recombination and the isomerization of the benzyl radicals occurs in solution.

The interface between the organic semiconductor and dielectric plays an important role in determining the device performance of organic field-effect transistors (OFETs). Although self-assembled monolayers (SAMs) made from organosilanes have been widely used for dielectric modification to improve the device performance of OFETs, they suffer from incontinuous and lack uniform coverage of the dielectric layer. Here, it is reported that by introduction of a solution-processed organozinc compound as a dielectric modification layer between the dielectric and the silane SAM, improved surface morphology and reduced surface polarity can be achieved. The organozinc compound originates from the reaction between diethylzinc and the cyclohexanone solvent, which leads to formation of zinc carboxylates. Being annealed at different temperatures, organozinc compound exists in various forms in the solid films. With organozinc modification, p-type polymer FETs show a high charge carrier mobility that is about two-fold larger than a control device that does not contain the organozinc compound, both for devices with a positive threshold voltage and for those with a negative one. After organozinc compound modification, the threshold voltage of polymer FETs can either be altered to approach zero or remain unchanged depending on positive or negative threshold voltage they have.

Two unreported C-glycosylated amino acid structures could be prepared by addition of an amino acid organozinc on carbohydrates bearing an aldehyde function. For this purpose, a new iodinated amino acid bearing a four-carbon side chain was conveniently prepared in two steps. Conversion into the corresponding organozinc reagent was optimal in acetonitrile using zinc/copper activated with 1,2-dibromoethane and trimethylsilyl chloride. A protocol was developed for the addition of this organozinc compound to simple aldehydes in acetonitrile using BF3 · OEt2 as a Lewis acid. When applied to riboside and glucoside aldehyde derivatives, this protocol led to new C-glycosylated amino acids in acceptable yields.

Organozinc compounds formed from 1-aryl-2,2-dibromoalkanes, α,α-dibromopinacoline, and dialkyl dibromomalonates and zinc react with (3-phenylprop-2-enylidene)malonodinitriles and primary amides of 2-cyano-5-phenylpenta-2,4-dienoic acid to form 2-alkyl-2-aroyl-3-(phenylvinyl)cyclopropan-1,1-dicarboxylic acid dinitriles, N-substituted amides of 3-(phenylvinyl)-2-(2,2-dimethylpropanoyl)-1-cyanocyclopropan-1-carboxylic acids, and alkyl 3-R-6-(phenylvinyl)-2,4-dioxo-5-cyano-3-azabicyclo[3.1.0]-hexan-1-carboxylates as a single stereoisomer.

Reformatsky reagent generated from methyl 1-bromocyclohexane-1-carboxylate reacted with N-aryl-2-oxochromene-3-carboxamides and N-aryl-6-bromo-2-oxochromene-3-carboxamides to give, depending on the conditions, the corresponding N-aryl-(6-bromo)-4-(1-methoxycarbonylcyclohexyl)-2-oxochroman-3-carboxamides or 3-aryl-(9-bromo)-1,1-pentamethylene-2,3,4,4a,5,10b-hexahydro-1H-chromeno[3,4-c]pyridine-2,4,5-triones. The products were isolated as a single diastereoisomer.

Organozinc compounds obtained by treatment of dialkyl 2,2-dibromomalonates with zinc reacted with N-substituted 2-oxochromene-3-carboxamides to give dialkyl 1a-R-carbamoyl-2-oxo-1a,7b-dihydro-2H-cyclopropa[c]chromene-1,1-dicarboxylates or alkyl 2-R-1,3,4-trioxo-2,3-dihydro-1H,9bH-chromeno[3′,4′:1,3]-cyclopropa[1,2-c]pyrrole-9c-carboxylates. Reactions of N-substituted 2-oxochromene-3-carboxamides with zinc enolates derived from methyl 4,4-dibromo-3-oxoalkanoates led to the formation of the corresponding 9c-alkyl-2-R-2,3-dihydrochromeno[3′,4′:1,3]cyclopropa[1,2-c]pyrrole-1,3,4-triones.

The reaction of 1,2-o-xylyl dichloride with activated zinc in THF gives the organozinc compound [(μ-o-xyl)Zn2Cl2(THF)4], 1, where xyl = (2-methanidylphenyl)methanide. The compound is stable in the solid state but undergoes a slow decomposition in solution to generate the μ4-oxo cluster [(μ-o-xyl)2Zn4(μ-Cl)2(μ4-O)(THF)4], 3, which has been characterised in the solid state by single-crystal X-ray techniques. The organozinc complex 1 catalyses the ring-opening of THF in the presence of PCl3 to give a mixture of the two compounds [Cl(CH2)4O]PCl2 and [Cl(CH2)4O]2PCl.

Factors determining the effect of ZnII ions on the catalytic activity of the NiII complexes with 2,2"-bipyridine (bpy) in the reduction of organohalides were elucidated by cyclic voltammetry and electrolysis. The mechanism proposed involves the reduction of the NiIIbpy complex to Ni0bpy, the oxidative addition of organohalides to the Ni0bpy complex, and nickel transmetallation with the cathode-generated Zn0 to form an organozinc compound.

The diastereoselective addition of the highly functionalized organozinc compound 1 to the aldehyde 2 in the presence of the chiral amino alcohol 3 (-->4) is a key step in the first total synthesis of (+)-halichlorine. A series of protections/deprotections and a macrolaconization complete the synthesis. Halichlorine selectively inhibits the expression of the cell adhesion molecule VCAM-1. TBS=tert-butyldimethylsilyl.

The first total synthesis of the antitumor agent roseophilin 1 is reported. Its intricate macrotricyclic core 2 is obtained by means of a new palladium-catalyzed manifold for the formation of ansa-bridged pyrroles which proceeds via vinyl oxirane 8 and allyl lactone 11 as key intermediates. After conversion of the latter into pyrrolophane 14, a base-induced elimination of the sulfone group followed by the Michael addition of a zincate onto the resulting enone 18 installs the isopropyl substituent in a stereoselective manner. The pyrrolylfuran side chain 3 of roseophilin is prepared from 4-methoxy-2(5H)-furanone (24) and methyl 4-chloropyrrole-2-carboxylate (26) as the starting materials. The appropriate building blocks 25a and 28 derived thereof are combined via a sequence comprising a directed metal−halogen exchange reaction, transmetalation of the resulting lithiopyrrole to the corresponding organozinc compound, a palladium-catalyzed cross coupling of the latter, and a subsequent acid-catalyzed closure ...

Organozinc compounds obtained by treatment of dialkyl 2,2-dibromomalonates with metallic zinc reacted with N-substituted 3-aryl-2-cyanoprop-2-enoic acid amides to give alkyl 3-R-6-aryl-5-cyano-2,4-dioxo-3-azabicyclo[3.1.0]hexane-1-carboxamides as a single stereoisomer.

Organozinc reagents have been used as a reliable tool to construct new C C covalent bonds owing to their ease of availability and high chemoselectivity. In the first section of this chapter, recent advances in the catalytic asymmetric addition reactions of organozinc reagents to the C X π bonds (X=O, N) are summarized together with some applications. These are classified according to particular organozinc compound, substrate, and chiral ligand, with the aim of providing a guide to aid selection of potential chiral ligands for addition reactions. Furthermore, relatively new aspects of organozinc addition, autocatalytic, and chirality switching reactions are discussed. In the second part of the chapter, recent advances regarding Reformatsky reagents are introduced with reference to their application to asymmetric reactions. Further expansion of this reaction for the synthesis of chiral fluorinated amino acids is also presented. As a final topic, radical reactions mediated by dialkylzinc reagents, which provide unique reactivity and selectivity compared with other radical initiators, are discussed.

Novel copolymers consisting of 3,3,3-trifluoro-1,2-epoxypropane (TFEP) and N-phenylmaleimide (PMI) units were prepared by the copolymerization of TFEP with PMI initiated with an organozinc compound. Using [Zn(OCH3)2 · (C2H5ZnOCH3)4] as an initiator, the copolymer chains consisted mainly of TFEP-TFEP sequences. The TFEP-PMI sequence content in the copolymer chains was small. On the other hand, using (C2H5ZnOCH3)4 as an initiator, only low molecular weight copolymers were formed. Those copolymers were suggested to have block structure, poly(TFEP)-block-poly(PMI), by the 19F NMR analysis. The copolymers showed higher thermostability than poly-(TFEP).

A protocol for the Lewis acid mediated addition of the new amino acid organozinc compound (VI) to simple aldehydes is developed and successfully applied to the synthesis of novel C-glycosylated amino acids such as (X).

The effects of Lewis acids (ZnCl 2 , AlCl 3 , BF 3 , and TiCl 4 ) on the generation of allylzinc species from allyl bromide and unactivated zinc powder in dry tetrahydrofuran (THF) were examined by trapping the organozinc compound with benzaldehyde, that is, Grignard-type allylation of the aldehyde. Among the Lewis acids employed, AlCl 3 was found to be the promoter of choice. The allylzinc species preformed in the presence of a catalytic amount of AlCl 3 effectively allylated carbonyl compounds. Various aromatic and aliphatic aldehydes as well as ketones were converted into homoallylic alcohols in good to excellent yields. Under the reaction conditions employed, ester, hydroxy, acetal, and aromatic nitro and halide groups were tolerated. In the case of α,β-unsaturated carbonyl compounds, selective 1,2-addition was observed. Substituted allyl bromides such as prenyl, crotyl, cinnamyl, and 2-cyclohexenyl bromides were smoothly converted to the corresponding allylzinc compounds, which reacted with carbonyl compounds to give substituted homoallylic alcohols in excellent yields. The diastereoselectivity in crotylation, cinnamylation, and 2-cyclohexenylation depended upon the structures of both the organic metals and the electrophiles. The origin of the observed selectivity is discussed. The allylation of dimethyl and cyclic acetals accompanied with carbon-oxygen bond cleavage also proceeded in excellent yields provided that two equivalents of AlCl 3 was present

The reaction which takes place between a carbonyl compound such as an aldehyde, ketone, or an ester, and an alpha-haloester in the presence of zinc is commonly known as the Reformatsky reaction. It represents an extension of the reactions of carbonyl compounds with a dialkylzinc or an alkylzinc halide, but possesses the advantage that the isolation of the organozinc compound is unnecessary. The process creates a new carbon-carbon linkage and involves the following: Formation of an organozinc halide; addition to the carbonyl group of the aldehyde or ketone, decomposition by dilute acids. Keywords: Reformatsky reaction; side reactions; halogen compounds; carbon chain; arylacetic acids; beta-ketoesters; variations; experimental conditions

The effects of Lewis acids (ZnCl 2 , AlCl 3 , BF 3 , and TiCl 4 ) on the generation of allylzinc species from allyl bromide and unactivated zinc powder in dry tetrahydrofuran (THF) were examined by trapping the organozinc compound with benzaldehyde, that is, Grignard-type allylation of the aldehyde. Among the Lewis acids employed, AlCl 3 was found to be the promoter of choice. The allylzinc species preformed in the presence of a catalytic amount of AlCl 3 effectively allylated carbonyl compounds. Various aromatic and aliphatic aldehydes as well as ketones were converted into homoallylic alcohols in good to excellent yields. Under the reaction conditions employed, ester, hydroxy, acetal, and aromatic nitro and halide groups were tolerated. In the case of α,β-unsaturated carbonyl compounds, selective 1,2-addition was observed. Substituted allyl bromides such as prenyl, crotyl, cinnamyl, and 2-cyclohexenyl bromides were smoothly converted to the corresponding allylzinc compounds, which reacted with carbonyl compounds to give substituted homoallylic alcohols in excellent yields. The diastereoselectivity in crotylation, cinnamylation, and 2-cyclohexenylation depended upon the structures of both the organic metals and the electrophiles. The origin of the observed selectivity is discussed. The allylation of dimethyl and cyclic acetals accompanied with carbon-oxygen bond cleavage also proceeded in excellent yields provided that two equivalents of AlCl 3 was present

2′-Hydroxy-6′-methoxyacetophenone was obtained in 66% yield from 3-methoxyphenol. In the key step, 3-methoxyphenol protected by means of ethylvinyl ether was selectively metallated at the 2-position with butyllithium. Addition of ZnCl2 to the aryllithium gave the corresponding organozinc compound, which readily reacted on acetyl chloride under palladium catalysis.

The diastereoselective addition of the highly functionalized organozinc compound 1 to the aldehyde 2 in the presence of the chiral amino alcohol 3 (-->4) is a key step in the first total synthesis of (+)-halichlorine. A series of protections/deprotections and a macrolaconization complete the synthesis. Halichlorine selectively inhibits the expression of the cell adhesion molecule VCAM-1. TBS=tert-butyldimethylsilyl.

Multicomponent reactions are processes in which at least three starting materials react together to form a final compound containing most of the starting atoms. They constitute one of the most efficient processes in synthetic organic chemistry. They are also more economical and environmentally friendly than classic organic reactions. Moreover, since they allow a straightforward access to large libraries of compounds containing the same core units, they represent a valuable tool for pharmaceutical industries, especially for high-throughput screening. In 2006, the laboratory developed a Mannich-type multicomponent reaction between aromatic organozinc compounds, aldehydes and secondary amines allowing the efficient preparation of diarylmethylamines. These structures, and more generally the α,α-disubstituted amine core unit, are found in a large range of compounds displaying diverse pharmacological properties. The main purpose of this PhD project was to extend the multicomponent process to other types of α,α-disubstituted amines. In the first part of this work, a range of β-arylethylamines, and in particular those bearing a carboxyethyl group at the position α to the nitrogen, have been prepared starting from in situ-generated benzylic organozinc compounds (Barbier-like conditions), carbonyl compounds and primary or secondary amines. These conditions present the advantage to avoid the pre-formation of the organometallic compound. Due to their broad potential applications, the synthesis of α-aminoesters has also been undertaken starting from functionalized aromatic organozinc species. It could be noticed that in this case, due to possible side-reactions, the formation of the organometallic reagent had to be undergone prior to the three-component coupling. In a second part of this work, diastereoselective versions of the reaction have been developed starting from chiral amines. Interesting results, regarding both chemical yields and diastereoselectivity, have been obtained, especially with (R)-phenylethylamine. Concomitantly, the mechanism was evaluated via the monitoring of the reaction by in-situ infrared spectroscopy (ReactIR apparatus). Data obtained should help to develop strategies for the further development of enantioselective versions of the reaction, Les réactions multicomposant sont des réactions faisant intervenir au minimum trois composés pour la préparation d'un produit contenant la majeure partie des atomes de départ. Elles constituent l'un des procédés les plus performants en synthèse organique. En diminuant les coûts et les rejets par rapports aux réactions classiques de chimie organique, elles sont également plus économes et plus respectueuses de l'environnement. De plus, en permettant la formation rapide et efficace d'une large librairie de molécules complexes à partir de substrats simples, elles représentent un outil à forte valeur ajoutée dans le domaine pharmaceutique pour l'élaboration de chimiothèques. Face à ces enjeux, le laboratoire a développé en 2006 une réaction multicomposant de type Mannich entre des organozinciques aromatiques, des amines secondaires et des aldéhydes. Cette réaction permet la synthèse en une étape d'une variété de diarylméthylamines, dont la structure amine α,α-disubstituée est rencontrée dans de nombreux composés d'intérêt pharmacologique. A partir de ces travaux, le premier objectif du projet de thèse a été d'étendre la réaction multicomposant à d'autres types d'amines α,α-disubstituées. Tout d'abord, la préparation de nombreuses β-aryléthylamines, et notamment d'α-aminoesters, a été mise au point de manière rapide et efficace à l'aide d'organozinciques benzyliques formés in situ dans des conditions de type Barbier. Ces conditions opératoires présentent l'avantage d'éviter l'étape préliminaire de formation de l'organozincique. En raison de l'intérêt de ces composés, la synthèse d'α-aminoesters à partir d'organozinciques aromatiques a ensuite été réalisée, en préformant l'organométallique à partir du dérivé bromé correspondant par une catalyse au cobalt. Au delà de l'extension de cette réaction, le deuxième objectif du projet de thèse a été de développer des versions diastéréosélectives de la réaction multicomposant à partir d'amines chirales. Des résultats corrects en termes de diastéréosélectivité ont été obtenus, notamment à l'aide de (R)-phényléthylamine. Dans un dernier temps, le mécanisme réactionnel a été étudié par suivi de la réaction par infrarouge à l'aide d'un appareillage ReactIR. Les données receuillies sur les intermédiaires réactionnels potentiels serviront de base pour l'élaboration de stratégies énantiosélectives

Xenalipin 1 (4′-trifluoromethyl-2-biphenylcarboxylic acid) was synthesized in the [14C]-labelled form with specific activity 21.0 mCi/mmol suitable for metabolism and distribution studies in animals. The synthetic sequence involved conversion of [14C]- benzoic acid to the 4,4-dimethyl-2-oxazoline derivative, formation of an organozinc compound, palladium-catalyzed coupling of the arylzinc-oxazoline with 4-trifluoromethyliodobenzene, and acid hydrolysis. The radiochemical purity was 99.4%.

Reaction of 2-(bromozincmethyl)-2-alkenyl ethers 1a,b,c,d with 1-(trimethylsilyl)-1-alkynes 2 afforded carbometallation products 3, which were converted by Pd(0)-catalyzed cyclization to 4-methylenecyclopentenes 5. The rates of both the addition and cyclization step depend on the concentration of the organozinc compound and the preparation of 5 is best performed using a 1.4–1.8 M solution of 1. At lower concentrations reaction times must be longer and, when 1c is reacted, the addition is incomplete and gives rise to a mixture of products (3 and 14), which on Pd(0)-treatment leads to a mixture of isomeric methylenecyclopentenes (5, 15 and 16).

1 Introduction: Scope and Definitions 2 Dialkylzinc Compounds 3 Monoalkylzinc Species 4 Dimethylzinc Radical Cation and Methylzinc Cation 5 Zinc–Cyanide Complexes Keywords: organozinc compound thermochemistry; dialkylzinc compounds; vaporization enthalpies; enthalpies of formation; monoalkylzinc species; dimethylzinc radical cation and methylzinc cation; zinc–cyanide complexes; thermochemical attention and carbon–zinc bonds

1 1,2-Metallate Rearrangements 2 Other Types of Rearrangements 3 Conclusions Keywords: organozinc compound rearrangement; methylene homologations; allylmetallation of alkenyl and alkynyl metals; Reformatsky reaction; methylene homologations in allene and olefin synthesis; alkynyl metal allylmetallation; Fritsch–Buttenberg–Wiechell rearrangement; five-membered carbo- and heterocycles

A convergent biomimetic synthesis of hemibrevetoxin B from d-glucal and d-arabinose utilizes an electrophile-promoted cascade anti-Baldwin cyclization of an epoxy alcohol. The epoxy alcohol arises from a palladium-catalyzed coupling of a highly functionalized organozinc compound and an alkenyl iodide, which serve as two chiral building blocks of similar size and complexity. This first successful implementation of a cascade epoxy alcohol cyclization for the synthesis of marine polycyclic ether toxins proceeds in 39 steps and 4% overall yield.

Highly reactive zinc metal was prepared by electrolysis of a DMF solution containing naphthalene and a supporting electrolyte in a one-compartment cell fitted with a platinum cathode and a zinc anode. This reactive zinc was used for efficient transformation of ethyl 2-bromoacrylate into the corresponding organozinc compound, which was reacted with various aryl iodides or bromides in the presence of 5 mol% Pd(P( o -Tol) 3 ) 2 Cl 2 to give the corresponding cross-coupling products in high yields. These cross-coupling reactions were successfully applied to a synthesis of the precursor of naproxen and cicloprofen, non-steroidal anti-inflammatory agent.

A three-component reaction between an aldehyde, metallated hexamethyldisilazane and a functionalized organozinc compound proceeded smoothly in the presence of LiClO4 in diethyl ether to afford primary amino esters in good yields.

Studies on the reaction of zinc alkyls with O2 are reported which demonstrate that the selective oxygenation of organozinc compound is viable. The reaction of [EtZn(azol)]n (azol = deprotonated 1-aziridineethanol) with an excess of dry O2 in toluene affords the zinc ethylperoxide [EtOOZn(azol)]2[EtZn(azol)]2, while the analogous reaction between Me2Zn and O2 results in the isolation of the Me6Zn7(OMe)8 cluster in high yield.

A new organozinc compound, zinc bis-2-(o-hydroxyphenyl)benzoxazolate, was prepared from 2-(o-hydroxyphenyl)benzoxazole and electroluminescent properties of the compound was investigated. An electroluminescent device was composed of glass substrate/indium-tin-oxide/hole transporting layer/zinc benzoxazolate/Al thin films. The electroluminescence of blue light was observed with the electric field of over 90 MV/m.

A new quantitative method to prepare the perfluoroalkyl ethanol (R F CH 2 CH 2 OH) via an organometallic route is described. The iodoperfluoroalkyl ethane (R F CH 2 CH 2 I) reacts with the metallic zinc-copper couple in particular solvents, especially butyl phosphate. The oxidation of the organozinc compound R F CH 2 CH 2 ZnI leads to an alcohol.

Diethylzinc and ethylzinc acetylacetonate were reacted with maleic and citraconic anhydrides. The structure of the products obtained upon hydrolysis showed these reactions to proceed via Michael type addition of the organozinc compound to the anhydride followed by subsequent C- and O-acylation reactions of the resulting intermediate adduct by the second anhydride molecule.

Diethylzinc was found to catalyze the carbonylation of amines including aromatic amines to give the corresponding formamides in good yields.

Syntheses and reactivities of organozinc enolates, having same structure as that of the chain end of growing poly(vinyl ketone) molecules, were studied. An addition reaction of ZnEt2 with ethyl styryl ketone gave an organozinc enolate, ethylzinc 5-phenyl-3-heptene-3-olate (ZE), fairly quantitatively. In the polymerization of ethyl isopropenyl ketone initiated with ethylzinc 1,3-diphenyl-1-pentene-1-olate (ZC), a second-order rate law with respect to ZC was established, suggesting a coordination-addition mechanism plausible for this reaction in a way similar to the previous result with phenyl styryl ketone. At the same time as the above studies, the chemical behavior of ZC and ZE toward carbon dioxide (CO2) was also examined. Through the measurements of time course of IR and NMR spectra of the reaction system, it was concluded that a polymeric form of organozinc enolates should be the final product formed in the reaction between ZC (or ZE) and CO2. This polymeric organozinc compound was able to catalyze the reaction of methyloxirane with CO2 to give rise to poly(propylene carbonate) and propylene carbonate.

The organozinc compound RCHCHCH2ZnBr (R = H, CH3, C2H5, C6H5, CH2CH) reacts with terminal α-acetylenic halides to give gem-disubstituted cyclopropanes, in good yield. Similar results are obtained with the compounds HCCCH2A, where A is a good leaving group (OC6H5, N+(R)3).

数種類の異なった性質をもったアルミナをつくり,これに種々の有機亜鉛化合物を加えた触媒系による,アルキレンオキシドの高重合反応についてしらべた。アルミナ単独による触媒活性は,アルミニウムイソプロポキシドを水蒸気で徐々に加水分解したのち,焼成してつくった非晶形のγ-アルミナが,各種アルミナの中で最も高活性であることがわかった。また,これらアルミナに,ジエチル亜鉛,エチル亜鉛アルコキシド,および,ジエチル亜鉛-アルコール系等を加えたものを触媒として,アルキレンオキシドを重合させると,アルミナ単独を触媒にする場合よりも,重合度の大きいポリマーが,高収率で生成するが,これらの,二元系または,三元系触媒においても,アルミナ自身の持つ,結晶形,結晶状態,酸性度などの特性が,触媒活性に大きく影響していることがわかった。これら,二元系および三元系触媒の高重合活性種は,アルミナの,-O-Al-O-結合と,エチル-亜鉛結合の両方が共存するときに形成されるものと考えられる。

1. A number of aliphatic, aromatic, and heterocyclic organozinc compounds of the RZnX class were prepared in the individual state and in the form of complexes with ether and with dioxane. 2. In structure the mixed organozinc compounds are not complex compounds of formula R2Zn·ZnX2, but correspond to the formula RZnX. 3. Mixed organozinc compounds of the RZnX class were isolated from the “Biaise reagent,” and their structure was proved.

Some unsymmetrical organozinc compounds of the RZnR′ class (R=phenyl or benzyl, R′=2-thienyl) and a number of unsymmetrical aliphatic organozinc compounds were synthesized.