Functionalized Organozinc Reagents Research Articles

Recent Advances in Cross-Couplings of Functionalized Organozinc Reagents

AbstractCross-couplings involving organozinc reagents usually require a Pd-catalyst (Negishi cross-coupling), however, uncatalyzed cross-couplings of zinc organometallics proceed well in the absence of transition-metal catalysts with reactive electrophiles such as benzal 1,1-diacetates, benzhydryl acetates, and iminium trifluoroacetates. Organozinc compounds also undergo C–N bond formation with O-benzoylhydroxylamines or organic azides in the presence of cobalt- or iron-catalysts. Highly diastereoselective and enantioselective cross-couplings can be readily performed with room-temperature configurationally stable alkylzinc species, producing diastereoselectively and enantiomerically enriched products. Finally, highly regioselective magnesiations of functionalized arenes and heteroarenes undergo Negishi (after transmetalation with ZnCl2) or Cu-catalyzed cross-couplings.1 Introduction2 Uncatalyzed Cross-Couplings of Organozinc Reagents with Highly Electrophilic Partners3 Iron- and Cobalt-Catalyzed Aminations using Organozinc Reagents4 Stereo- and Regioselective Cross-Couplings of Organozinc Reagents5 Conclusion

Direct Arylation of Benzyl Ethers with Organozinc Reagents.

A novel C(sp3)-H bond arylation of benzyl ethers with Knochel-type arylzinc reagents has been developed. This transition-metal-catalyst-free reaction proceeds well under mild conditions in a simple and effective manner and enables the synthesis of a wide range of potentially biologically active benzyl ethers by using highly functionalized organozinc reagents as a carbon nucleophile.

Functionalized Organozinc Reagents in Medicinal Chemistry: Discovery of Novel Drug Candidates

Discovery, optimization, and early development of drug candidates are very challenging and require a versatile synthetic chemistry toolbox. Organozinc chemistry is a powerful methodology for carbon–carbon bond formation which tolerates several functional groups that are critical for maintaining good physicochemical properties of drug molecules. Here we demonstrate that organozinc chemistry offers facile solutions to otherwise challenging medicinal chemistry problems commonly encountered during lead optimization. In this review, we summarize several examples in which utilization of organozinc-mediated couplings enabled us to rapidly explore a medicinal chemistry hypothesis using readily available intermediates. This chemistry allowed us to make rapid decisions with limited chemistry resources. 1 Introduction 2.1 Alpha4 Integrin Antagonists 2.2 CRTH2 Antagonists 2.3 Glucokinase (GK) Activators 2.4 Leukotriene B4 (LTB4) Receptor Antagonists 2.5 Janus Activated Kinase 3 (JAK3) Inhibitors 2.6 Synthesis of Novel Scaffolds 3 Conclusions 4 Experimental Methods

CuI catalyzed sulfonylation of organozinc reagents with sulfonyl halides.

In this study, a facile CuI catalyzed synthesis of sulfones involving a nucleophilic addition of functionalized organozinc reagents to organic sulfonyl chlorides is realized. This reaction proceeds efficiently at room temperature, giving rise to various functional group substituted sulfones, generally in moderate to high yields. The method provides a novel, simple, and promising strategy for functionalized sulfone synthesis in the research field of sulfur chemistry.

ChemInform Abstract: Pd‐ and Ni‐Catalyzed Cross‐Coupling Reactions of Functionalized Organozinc Reagents with Unsaturated Thioethers.

AbstractVarious thiomethylated hetarenes and alkynes are coupled with aryl, benzylic, and alkylzinc halides in the presence of a transition‐metal catalyst system.

ChemInform Abstract: Direct Addition of Functionalized Organozinc Reagents to Carbon Dioxide, Ketones, and Aldehydes in the Presence of MgCl2.

AbstractEfficient addition of functionalized organozinc reagents to various carbonyl derivatives and CO2 is achieved in the presence of MgCl2.

Pd‐ and Ni‐Catalyzed Cross‐Coupling Reactions of Functionalized Organozinc Reagents with Unsaturated Thioethers

A variety of unsaturated thioethers have been subjected to cross-coupling reactions with functionalized zinc reagents in the presence of a transition-metal catalyst. Three different catalytic systems based on Pd(OAc)(2) or [Ni(acac)(2)] and the ligands S-Phos or DPE-Phos gave the best results. N-Heterocyclic thioethers based on a pyridine, pyrimidine, pyrazine, pyridazine, triazine, benzothiazole, benzoxazole, pyrrole, or quinazoline ring, as well as thiomethylacetylenes, serve as electrophiles in this cross-coupling reaction. Aryl-, heteroaryl-, benzylic, and alkylzinc halides with sensitive functionalities, such as ester, nitrile, or ketone groups react at ambient temperature with unsaturated thioethers using a Ni catalyst. The corresponding Pd-catalyzed reactions require slightly higher temperatures. Large-scale cross-coupling experiments (10-20 mmol) with N-heterocycles are also reported.

Efficient Preparation of Polyfunctional Indoles via a Zinc Organometallic Variation of the Fischer Indole Synthesis

Functionalized organozinc reagents readily react with various aryldiazonium salts furnishing regioselectively polyfunctional indoles after heating with microwave irradiation. This new organometallic variation of the Fischer indole synthesis tolerates a wide range of functional groups and can be readily scaled up.

Direct Addition of Functionalized Organozinc Reagents to Carbon Dioxide, Ketones, and Aldehydes in the Presence of MgCl2

A variety of functionalized organozinc reagents undergo smooth addition reactions at ambient temperature to carbon dioxide, ketones, and aldehydes in the presence of stoichiometric amounts of MgCl2. Several reactions were performed on a 20 mmol scale.

ChemInform Abstract: MgCl2‐Accelerated Addition of Functionalized Organozinc Reagents to Aldehydes, Ketones, and Carbon Dioxide.

AbstractThe reactivity of functionalized arylzinc and benzylzinc reagents is significantly improved in the presence of MgCl2.

ChemInform Abstract: A Novel Palladium‐Catalyzed Cross‐Coupling of Thiomethylated Alkynes with Functionalized Organozinc Reagents.

AbstractThe method is carried out at moderate temperature without the need for copper salts.

Scaled-Up Transition-Metal-Catalyzed Cross-Coupling Reactions of Thioether-Substituted N-Heterocycles with Organozinc Reagents

A variety of functionalized methylthio-substituted N-heterocycles (pyridines, pyrimidines, pyrazines, pyridazines, triazines, quinazolines, benzothiazoles) undergo smooth palladium- or nickel-catalyzed cross-couplings with highly functionalized organozinc reagents at ambient temperature. No expensive copper(I) salts are required and the coupling reactions proceed readily in the range of up to 20 mmol scale.

MgCl2‐Accelerated Addition of Functionalized Organozinc Reagents to Aldehydes, Ketones, and Carbon Dioxide

The reactivity of functionalized arylzinc and benzylzinc reagents is significantly improved in the presence of MgCl2.

ChemInform Abstract: Room‐Temperature Cross‐Coupling of Highly Functionalized Organozinc Reagents with Thiomethylated N‐Heterocycles by Nickel Catalysis.

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.

A Novel Palladium-Catalyzed Cross-Coupling of Thiomethylated Alkynes with Functionalized Organozinc Reagents

A range of methylthio-substituted acetylenes undergo smooth palladium-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, and alkylzinc reagents using the Pd(OAc)2/DPE-Phos catalytic system at 25 or 50 ˚C without the need for copper salts.

Room Temperature Cross-Coupling of Highly Functionalized Organozinc Reagents with Thiomethylated N-Heterocycles by Nickel Catalysis

A variety of thiomethyl-substituted N-heterocycles such as pyridines, isoquinolines, pyrimidines, pyrazines, pyridazines, quinazolines, triazines, benzothiazoles, or benzoxazoles undergo smooth Ni-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, alkyl-, and benzylic zinc reagents using an inexpensive Ni(acac)(2)/DPE-Phos catalytic system at 25 degrees C.

ChemInform Abstract: Pd‐Catalyzed Cross‐Coupling of Functionalized Organozinc Reagents with Thiomethyl‐Substituted Heterocycles.

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.

Pd-Catalyzed Cross-Coupling of Functionalized Organozinc Reagents with Thiomethyl-Substituted Heterocycles

Various thiomethyl-substituted N-heterocycles (pyridines, pyrimidines, pyrazines, pyridazines, triazines, benzothiazoles, benzoxazoles, pyrazoles, benzindazoles, quinazolines, etc.) undergo smooth Pd-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, benzylic-, and alkylzinc reagents using Pd(OAc)(2)/S-Phos as the catalytic system mostly at 25 degrees C. No copper salt is required to perform these reactions.

Transition-Metal-Free Carboxylation of Organozinc Reagents Using CO2in DMF Solvent

An efficient process for the carboxylation of functionalized organozinc reagents with CO(2) under transition-metal-free conditions was developed by employing DMF solvent in the presence of LICl.

ChemInform Abstract: Nickel(II)‐Catalyzed Carbon—Carbon Bond Formation Reaction of Functionalized Organozinc Reagents with Aromatic Aldehydes.

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.