Aliphatic Grignard Reagents Research Articles

Iron‐<i>N</i>,<i>N</i>,<i>N</i>’,<i>N</i>’‐Tetramethylethylenediamine‐Catalyzed Selective Substitution of Functionalized Diene and Triene Monoepoxides with Aliphatic Grignard Reagents

When γ,δ‐epoxy‐α,β‐unsaturated esters were treated with 3 equiv. of aliphatic Grignard reagents in the presence of 10 and 20 mol% of FeCl<sub>2</sub> and <i>N</i>,<i>N</i>,<i>N</i>’,<i>N</i>’‐tetramethylethylenediamine (TMEDA), regio‐ and stereoselective substitution of the epoxide moiety with the aliphatic Grignard reagent occurred to give exclusively δ‐hydroxy‐γ‐alkyl‐α,β‐unsaturated esters in high yields. In addition, γ,δ‐epoxy‐α,β,ε,ζ‐unsaturated esters and amides afford the corresponding δ‐hydroxy‐γ‐alkyl‐α,β,ε,ζ‐unsaturated esters and amides, respectively, with high selectivity.

Visible‐Light‐Promoted Iron‐Catalyzed C(sp2)–C(sp3) Kumada Cross‐Coupling in Flow

AbstractA continuous‐flow, visible‐light‐promoted method has been developed to overcome the limitations of iron‐catalyzed Kumada–Corriu cross‐coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes’ residence time, considerably enhancing the applicability of this iron‐catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application.

Visible-Light-Promoted Iron-Catalyzed C(sp2 )-C(sp3 ) Kumada Cross-Coupling in Flow.

A continuous‐flow, visible‐light‐promoted method has been developed to overcome the limitations of iron‐catalyzed Kumada–Corriu cross‐coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes’ residence time, considerably enhancing the applicability of this iron‐catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application.

Manganese-Catalyzed Kumada Cross-Coupling Reactions of Aliphatic Grignard Reagents with N-Heterocyclic Chlorides

Herein we report the use of manganese(II) chloride for the catalytic generation of C(sp2)–C(sp3) bonds via Kumada cross-coupling. Rapid and selective formation of 2-alkylated N-heterocyclic complexes were observed in high yields with use of 3 mol% MnCl2THF1.6 and under ambient reaction conditions (21 °C, 15 min to 20 h). Manganese-catalyzed cross-coupling is tolerant toward both electron-donating and electron-withdrawing functional groups in the 5-position of the pyridine ring, with the latter resulting in an increased reaction rate and a decrease in the amount of nucleophile required. The use of this biologically and environmentally benign metal salt as a catalyst for C–C bond formation highlights its potential as a catalyst for the late-stage functionalization of pharmaceutically active N-heterocyclic molecules (e.g., pyridine, pyrazine).

ChemInform Abstract: Copper‐Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to Methyl 4,4,4‐Trifluorocrotonate: Synthesis of Enantioenriched Trifluoromethylated Compounds.

Copper-catalyzed enantioselective 1,4-conjugate addition of methyl 4,4,4-trifluorocrotonate with aliphatic Grignard reagents to access an asymmetric tertiary carbon center attached with a trifluoromethyl group was achieved under mild reaction conditions. The desired products could be obtained in reasonable yields and good enantioselectivities.

Copper‐Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to Methyl 4,4,4‐Trifluorocrotonate: Synthesis of Enantioenriched Trifluoromethylated Compounds

Copper-catalyzed enantioselective 1,4-conjugate addition of methyl 4,4,4-trifluorocrotonate with aliphatic Grignard reagents to access an asymmetric tertiary carbon center attached with a trifluoromethyl group was achieved under mild reaction conditions. The desired products could be obtained in reasonable yields and good enantioselectivities.

Reactions of Grignard Reagents with Nitrous Oxide

The chemical activation of nitrous oxide (N2O) can be achieved by organocalcium, organosodium, and organolithium compounds. Grignard reagents, on the other hand, are believed to be inert. We demonstrate that this generalization is not correct. Some aliphatic Grignard reagents undergo a rapid conversion when subjected to an atmosphere of N2O. Hydrazones are the main reaction products.

The Grignard Reaction of Cyclodextrin‐6‐aldehydes Revisited: A Study of the Stereoselectivity Upon Addition of Organometallic Reagents to Aldehydes and Ketones

Abstract2A–G,3A–G,6B–G‐Icosakis‐O‐benzyl‐6A‐O‐oxo‐β‐cyclodextrinwas treated with aromatic and aliphatic Grignard reagents to give diastereomeric mixtures of the secondary alcohols with remarkable difference in polarity. Moderate‐to‐good yields and selectivity were obtained. By oxidizing the secondary alcohols, followed by a second Grignard reaction, good to excellent yields and selectivity of tertiary alcohols could be obtained. The stereochemistry of the reaction outcome was shown to be dependent on the order of addition of the Grignard reagents and could be efficiently controlled.

ChemInform Abstract: Cobalt‐Catalyzed Cross‐Coupling Reaction Between Functionalized Primary and Secondary Alkyl Halides and Aliphatic Grignard 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.

Cobalt‐Catalyzed Cross‐Coupling Reaction between Functionalized Primary and Secondary Alkyl Halides and Aliphatic Grignard Reagents

AbstractThe coupling of primary and secondary unactivated alkyl bromides with alkyl‐Grignard reagents was performed in good yields under mild conditions by using a new catalytic system: consisting of cobalt chloride and tetramethylethylenediamine (CoCl2⋅2 LiI, 4 TMEDA). The reaction is very chemoselective since ketone, ester and nitrile functions are tolerated.

Complexation Promoted Additions to N‐Benzoyliminopyridinium Ylides. A Novel and Highly Regioselective Approach to Polysubstituted Piperidines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Complexation promoted additions to N-benzoyliminopyridinium ylides. A novel and highly regioselective approach to polysubstituted piperidines.

Unprecedented regioselectivities were observed for the addition of different organometallic nucleophiles to N-benzoyliminopyridinium ylides. Even benzylic and branched aliphatic Grignard reagents, which usually give substantial amounts of 1,4-adducts, showed excellent 1,2-regioselectivities. The electronic nature of the pyridinium ylide is taken into account to explain these results.

New entry to alicyclic amines via alkylative fragmentation of cyclic aminoaldehyde tosylhydrazones

Tosylhydrazones of cyclic aminoaldehydes when exposed to aromatic and aliphatic Grignard reagents produce ring-opened acyclic unsaturated primary carbamates and carbamate alcohols in good yields.

ChemInform Abstract: Enantioselective 1,4‐Addition of Aliphatic Grignard Reagents to Enones Catalyzed by Readily Available Copper(I) Thiolates Derived from TADDOL.

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.

The Reaction of 1,3-Disubstituted Benzimidazolium Salts With Grignard Reagents and A Novel Synthetic Method for Aldehydes

Abstract Aliphatic and aromatic Grignard reagents have been found to add to the double bond of 1, 3-disubstituted benzimidazolium salts. The resulting substituted benzimidazolines were hydrolyzed and the aldehydes converted directly to their 2, 4-dinitrophenylhydrazone derivatives. The scope and limitations of this synthesis are discussed.

Prediction of the Optimum Reaction Time for Carbon-11 Labelling Reactions. The Rate Constants for the Carboxylation of Grignard Reagents

Abstract The rate constants for the carboxylation of a series of aliphatic Grignard reagents were measured as part of the development of a computer assisted automated synthesis apparatus. A good correlation was obtained between the rate constants and Taft’s Es values.

Metal-halogen exchange between polybromoanisoles and aliphatic Grignard reagents: a synthesis of cyclopenta[b]benzofurans

Metal-halogen exchange between polybromoanisoles and aliphatic Grignard reagents: a synthesis of cyclopenta[b]benzofurans

Synthesis of long-chain methyl-branched 1-alkynes from alkylmagnesium halides and methoxyallene

The reaction of methoxyaliene with aliphatic Grignard reagents gave methyl-branched terminal acetylenes.

A stereospecific route to olefins through sequential coupling reaction of Grignard reagents with 1-bromo-2-phenylthioethene in the presence of nickel or palladium catalysts

The room temperature sequential formation of two C–C bonds by reaction of aromatic or aliphatic Grignard reagents with (E)- or (Z)-1-bromo-2-phenylthioethene in the presence of nickel(II) or palladium(II) catalysts provides a novel stereospecific route to a variety of (E)- or (Z)-olefins of the R–CHCH–R and R1–CHCH–R2 type, with a stereoselectivity higher than 99% for the (E) isomers and in the range 95–98% or the (Z) isomers.

Reactions of conjugated arylazocyclohexenes with Grignard reagents. Part 2. A new stereospecific route to 2-alkyl- and 2-aryl-cyclohexanones

4-Methyl- and 4-t-butyl-1-arylazocyclohexenes react with aliphatic and aromatic Grignard reagents, to furnish, after oxidative hydrolysis of the intermediate aryihydrazones, 2-alkyl-4-methyl-, 2-aryl-4-methyl-, 2-alkyl-4-tbutyl-, and 2-aryl-4-t-butyl-cyclohexanones, with a trans-configuration. From the reactions with o-tolyl- and α-naphthyl-magnesium bromide only the cis-isomers were obtained. The structures of the products were, determined by spectroscopic methods and by epimerization of the trans-cyclohexanones into the more stable cis-isomers.