Organozinc Species Research Articles

Solid Organozinc Pivalates: A New Class of Zinc Organometallics with Greatly Enhanced Air- and Moisture-Stability

Organozinc species are powerful reagents for performing carbon–carbon and carbon–heteroatom bond-forming reactions in the presence of a transition-metal catalyst. However, extended applications of zinc reagents have been hampered by their moderate air- and moisture­-stability. This short review presents our recent developments on the preparation of solid aryl, benzyl, heteroaryl, allyl zinc pivalates and zinc amide enolate reagents with greatly enhanced stability toward to air and moisture.1 Introduction2 Preparation of Organozinc Pivalates2.1 Using Organic Halides as Substrates2.2 Using a Directed Metalation on Functionalized Arenes and Heteroarenes2.3 Preparation of Solid Allylic Zinc Pivalates3 General Reactivity Patterns of Organozinc Pivalates3.1 General Aspects3.2 Transition-Metal-Catalyzed Cross-Couplings3.3 Other Carbon–Carbon Bond-Forming Reactions Using Organozinc Pivalates3.4 Preparation and Reactions of Solid, Salt-Stabilized Zinc Amide Enolates as New, Convenient Reformatsky Reagents4 Conclusion

ChemInform Abstract: Cobalt‐Catalyzed Electrophilic Cyanation of Arylzinc Halides with N‐Cyano‐N‐phenyl‐p‐methylbenzenesulfonamide (NCTS).

AbstractThe cobalt catalyst can be used for the synthesis of the intermediate organozinc species and for the coupling reaction.

ChemInform Abstract: α‐C‐Glycosides via syn Opening of 1,2‐Anhydro Sugars with Organozinc Compounds in Toluene/n‐Dibutyl Ether.

AbstractThe diastereoselective addition of organozinc species to 1,2‐anhydro sugars in toluene/n‐dibutyl ether solvent is reported.

α-C-Glycosides via syn Opening of 1,2-Anhydro Sugars with Organozinc Compounds in Toluene/n-Dibutyl Ether.

The diastereoselective addition of organozinc species to 1,2-anhydro sugars in toluene/n-dibutyl ether solvent is reported. Compared to the existing methods, the reaction proceeds at 0 °C, and only a slight excess of nucleophile is required to achieve good yields. Scope was assessed with different O-protected glycals along with various nucleophiles (aryl, alkynyl). This methodology was applied to the synthesis of the α-anomer of canagliflozin.

Cobalt‐Catalyzed Electrophilic Cyanation of Arylzinc Halides with N‐Cyano‐N‐phenyl‐p‐methylbenzenesulfonamide (NCTS)

AbstractThe cobalt‐catalyzed cross‐coupling of organozinc bromides with N‐cyano‐N‐phenyl‐p‐methylbenzenesulfonamide (NCTS) is described. The same cobalt catalyst, cobalt(II) bromide, was used for both the synthesis of the organozinc species and the cross‐coupling reaction. However in this case, a catalytic amount of zinc dust is necessary in the second step to release the low‐valent cobalt. Under these mild conditions, moderate to excellent yields of different benzonitriles were obtained.magnified image

Preparation of an Arenylmethylzinc Reagent with Functional Groups by Chemoselective Cross-Coupling Reaction of Bis(iodo­zincio)methane with Iodoarenes

Palladium-catalyzed cross-coupling reaction of bis(iodozincio)methane with iodoarenes carrying various functionalities such as ester, boryl, cyano, and halo groups proceeded chemoselectively to give the corresponding arenylmethylzinc species efficiently. The moderate reactivity of the <i>gem</i>-dizinc reagent imparted functional group tolerance to the process. The transformations from iodoheteroarenes were also performed; in the case of iodopyridine derivatives, the nickel-catalyzed reaction gave the corresponding organozinc species efficiently. The obtained arenylmethylzinc species underwent the copper-mediated coupling reaction with a range of organic halides.

ChemInform Abstract: Aziridinylethers as Highly Enantioselective Ligands for the Asymmetric Addition of Organozinc Species to Carbonyl Compounds.

AbstractNew chiral aziridinylether ligands are synthesized.

ChemInform Abstract: N‐Trityl‐Aziridinyl Alcohols as Highly Efficient Chiral Catalysts in Asymmetric Additions of Organozinc Species to Aldehydes.

ChemInform Abstract: N‐Trityl‐Aziridinyl Alcohols as Highly Efficient Chiral Catalysts in Asymmetric Additions of Organozinc Species to Aldehydes.

ChemInform Abstract: Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions.

The Negishi cross-coupling is a powerful CC bond forming reaction. The method is less commonly used relative to other cross-coupling methods in part due to lack of availability of organozinc species. While organozinc species can be prepared, problems with reproducibility and handling of these sensitive species can complicate these reactions. Herein, we describe the continuous formation, using an activated packed-bed of metallic zinc, and subsequent use of organozinc halides. We demonstrate that a single column of zinc can provide excellent yields of organozinc halides and that they can be used downstream in subsequent Negishi cross-couplings. The preparation of the zinc column and the scope of the reaction are discussed.

ChemInform Abstract: Synthesis of gem‐Difluorinated Nitroso Compounds.

A method for the synthesis of gem-difluorinated nitroso compounds is described. The reaction involves interaction of organozinc reagents with (bromodifluoromethyl)trimethylsilane followed by nitrosation of difluorinated organozinc species with an n-butyl nitrite/chlorotrimethylsilane system.

Aziridinylethers as highly enantioselective ligands for the asymmetric addition of organozinc species to carbonyl compounds

In the present paper a straightforward and efficient method for the synthesis of new chiral aziridinylether systems has been described. All of the new compounds have been tested in two stereocontrolled addition reactions of organozinc species to carbonyl compounds. The addition of diethyl- and phenylethynylzinc to aryl and alkyl aldehydes afforded the corresponding chiral products in high chemical yields (up to 90%) and with excellent ee’s of approximately 93%.

N-Trityl-aziridinyl alcohols as highly efficient chiral catalysts in asymmetric additions of organozinc species to aldehydes

A synthetic route leading to a series of new chiral catalysts containing the N-trityl-aziridine moiety and a primary and a secondary hydroxyl group as nucleophilic centers is described. All the new compounds have been tested as chiral catalysts in the enantioselective addition of diethylzinc and phenylethynylzinc to aryl and alkyl aldehydes, yielding the corresponding chiral alcohols in high chemical yields (up to 96%) and with excellent ee’s of ca. 90%. The influence of the stereogenic centers located at the carbon atom bonded with the hydroxyl moiety and on the carbon of the aziridine ring on the stereochemistry of the addition reactions is also discussed.

Synthesis of gem-difluorinated nitroso compounds.

A method for the synthesis of gem-difluorinated nitroso compounds is described. The reaction involves interaction of organozinc reagents with (bromodifluoromethyl)trimethylsilane followed by nitrosation of difluorinated organozinc species with an n-butyl nitrite/chlorotrimethylsilane system.

Reactions of aldehdydes with organozinc reagents derived from (E)-3-bromo- and (E)-3-iodo-1-phenylsulfonylprop-1-ene

E)-3-Bromo-1-phenylsulfonylprop-1-ene and (E)-3-iodo-1-phenylsulfonylprop-1-ene both form allylic organozinc reagents that react with aromatic aldehydes to give mainly 4-aryl-4-hydroxy1-phenylsulfonylbut-1-enes. In contrast, reactions of the same organozinc species with 2-methylpropanal or 3-methylbutanal gave mixtures of diastereoisomeric 4-hydroxy-1-phenylsulfonylalk1-enes and 4-hydroxy-3-phenylsulfonylalk-1-enes.

Reactions of organozinc reagents with potassium bromodifluoroacetate

Assembling of gem -difluorinated compounds from organozinc reagents, potassium bromodifluoroacetate and electrophiles is described. • Synthesis of gem -difluorinated compounds. • Preparation and reactions of fluorinated organozinc reagents. • Reactions of potassium boromodifluoroacetate. A practical method for the synthesis of gem -difluorinated compounds from organozinc reagents is described. Potassium bromodifluoroacetate serves as a source of CF 2 -fragment, which is inserted into carbon zinc bond of organozinc reagents. The intermediate difluorinated organozinc species can be protonated, brominated or coupled with allylic electrophiles.

Cobalt‐Catalyzed Cross‐Coupling of Organozinc Halides with Bromoalkynes

AbstractThe cobalt‐catalyzed cross‐coupling of organozinc bromides is described. In the case of arylzinc reagents, the same cobalt catalyst, CoBr2(phen), can be used for both the synthesis of the organozinc species and the cross‐coupling reaction. In the case of alkylzinc halides, which allow access to dialkylalkynes, the method used for the preparation of the organozinc species has a significant impact on the yields.magnified image

ChemInform Abstract: Palladium‐Catalyzed Coupling Reaction of Perfluoroarenes with Diarylzinc Compounds.

This report describes the first Pd(0)-catalyzed cross-coupling of hexafluorobenzene (C6F6) with diarylzinc compounds to give a variety of pentafluorophenyl arenes. This reaction could be applied to other perfluoroarenes, such as octafluorotoluene, pentafluoropyridine, and perfluoronaphthalene, to give the corresponding polyfluorinated coupling products. The optimal ligand in this catalytic reaction was PCy3 , and lithium iodide was indispensable as an additive for the coupling reaction. One of the roles of lithium iodide in this catalytic reaction was to promote the oxidative addition of one C-F bond of C6F6 to palladium. Stoichiometric reactions revealed that an expected oxidative-addition product, trans-[Pd(C6F5)I(PCy3)2], generated from the reaction of [Pd(PCy3)2] with C6F6 in the presence of lithium iodide, was not involved in the catalytic cycle. Instead, a transient three-coordinate, monophosphine-ligated species, [Pd(C6F5)I(PCy3)], emerged as a potential intermediate in the catalytic cycle. Therefore, we isolated a novel Pd(II) complex, [Pd(C6F5)I(PCy3)(py)], in which pyridine (py) acted as a labile ligand to generate the transient species. In fact, in the presence of lithium iodide, this Pd(II) complex was found to react smoothly with diphenylzinc to give the desired pentafluorophenyl benzene, whereas the same reaction conducted in the absence of lithium iodide resulted in a decreased yield of pentafluorophenyl benzene, which indicated that the other role of lithium iodide was to enhance the reactivity of the organozinc species during the transmetalation step.

ChemInform Abstract: Limonene Oxide Derived Aziridinyl Alcohols as Highly Efficient Catalysts for Asymmetric Additions of Organozinc Species to Aldehydes.

AbstractChiral ligands synthesized from (+)‐limonene oxide and optically active aziridines are prepared and examined as catalyst for the addition of diethylzinc or in situ generated phenylethynylzinc to aldehydes.

Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions

AbstractThe Negishi cross‐coupling is a powerful CC bond forming reaction. The method is less commonly used relative to other cross‐coupling methods in part due to lack of availability of organozinc species. While organozinc species can be prepared, problems with reproducibility and handling of these sensitive species can complicate these reactions. Herein, we describe the continuous formation, using an activated packed‐bed of metallic zinc, and subsequent use of organozinc halides. We demonstrate that a single column of zinc can provide excellent yields of organozinc halides and that they can be used downstream in subsequent Negishi cross‐couplings. The preparation of the zinc column and the scope of the reaction are discussed.magnified image

ChemInform Abstract: Lactic Acid Derived Aziridinyl Alcohols as Highly Effective Catalysts for Asymmetric Additions of an Organozinc Species to Aldehydes.

ChemInform Abstract: Lactic Acid Derived Aziridinyl Alcohols as Highly Effective Catalysts for Asymmetric Additions of an Organozinc Species to Aldehydes.