Unactivated Alkyl Bromides Research Articles

Alkyl-aryl ketone synthesis via nickel-catalyzed reductive coupling of alkyl halides with aryl acids and anhydrides.

The present work disclosed a considerably improved method for the construction of alkyl-aryl ketones by the direct coupling of unactivated alkyl bromides with 1.5 equiv. of acids. In addition, the synthesis of aroyl C-glycosides was first achieved by the reductive coupling of 1-glycosyl bromides with acid derivatives, which may otherwise require multi-step synthesis.

Ni-catalyzed reductive coupling of alkyl acids with unactivated tertiary alkyl and glycosyl halides.

This work highlights Ni-catalyzed reductive coupling of alkyl acids with alkyl halides, particularly sterically hindered unactivated tertiary alkyl bromides for the production of all carbon quaternary ketones. The reductive strategy is applicable to α-selective synthesis of saturated, fully oxygenated C-acyl glycosides through easy manipulations of the readily available sugar bromides and alkyl acids, avoiding otherwise difficult multistep conversions. Initial mechanistic studies suggest that a radical chain mechanism (cycle B, Scheme 1) may be plausible, wherein MgCl2 promotes the reduction of Ni(II) complexes.

Nucleophilic Difluoro(phenylsulfonimidoyl)methylation of Unactivated Alkyl Bromides with PhSO(NTBS)CF2H: Facile Entry into gem‐Difluoroalkenes

AbstractAn efficient nucleophilic difluoro(phenylsulfonimidoyl)methylation of unactivated primary alkyl bromides with PhSO(NTBS)CF2H has been developed. It is particularly remarkable that, when 1.5 equiv. of alkyl bromides are used, the substitution products are obtained in moderate to excellent yields. The prepared difluoro(phenylsulfonimidoyl)methylated alkanes can be readily transformed to gem‐difluoroalkenes via base‐mediated β‐elimination reaction.

Cover Picture: Nucleophilic Difluoro(phenylsulfonimidoyl)methylation of Unactivated Alkyl Bromides with PhSO(NTBS)CF2H: Facile Entry into gem‐Difluoroalkenes (Chin. J. Chem. 8/2014)

Cover Picture: Nucleophilic Difluoro(phenylsulfonimidoyl)methylation of Unactivated Alkyl Bromides with PhSO(NTBS)CF₂H: Facile Entry into <i>gem</i>‐Difluoroalkenes (Chin. J. Chem. 8/2014)

Ni-catalyzed carboxylation of unactivated primary alkyl bromides and sulfonates with CO2.

A Ni-catalyzed carboxylation of unactivated primary alkyl bromides and sulfonates with CO2 at atmospheric pressure is described. The method is characterized by its mild conditions and remarkably wide scope without the need for air- or moisture-sensitive reagents, which make it a user-friendly and operationally simple protocol en route to carboxylic acids.

ChemInform Abstract: Photoredox Transformations with Dimeric Gold Complexes.

AbstractA light‐enabled reductive radical reaction of various unactivated alkyl and aryl bromides in the presence of a dimeric gold‐phosphine complex as catalyst is described.

A simple and efficient copper oxide-catalyzed Barbier–Grignard reaction of unactivated aryl or alkyl bromides with ester

An efficient one-pot route to synthesize tertiary alcohol compounds using Barbier–Grignard reaction of unactivated alkyl or aryl bromides with ester in THF at 65°C catalyzed by CuO has been developed and systematically investigated. A wide range of substituted tertiary alcohol compounds were obtained in good to high yields. The reaction is highly chemoselective. The mechanism involving the leaving group of R2O-group is discussed.

Corrigendum: Nickel‐Mediated Inter‐ and Intramolecular Reductive Cross‐Coupling of Unactivated Alkyl Bromides and Aryl Iodides at Room Temperature

It has been noticed by the authors that Scheme 8 in their Full Paper was incorrectly drawn. The correct Scheme 8 is provided below. The authors apologize for the oversight.

Ni-Catalyzed Reductive Homocoupling of Unactivated Alkyl Bromides at Room Temperature and Its Synthetic Application

A room-temperature Ni-catalyzed reductive approach to homocoupling of unactivated primary, secondary, and tertiary alkyl bromides is described. The catalytic system can be easily generated from air-stable and cheap materials and demonstrates broad functional group tolerance, thus allowing facile access to useful dimeric triterpene and lignan-like molecules. Moreover, the dimerization of tertiary bromide 6 efficiently establishes sterically hindered vicinal quaternary carbons (C3a and C3a'), which is a key linkage of intriguing bispyrrolo[2,3-b]indoline alkaloids, thereby enabling us to complete the total syntheses of racemic chimonanthine (9) and folicanthine (10). In addition, this dimerization method can be expanded to the highly stereoselective synthesis of bisperhydrofuro[2,3-b]furan (5a) and the dimeric spiroketal 5b, signifying the involvement of possible radical species.

ChemInform Abstract: Nickel‐Mediated Inter‐ and Intramolecular Reductive Cross‐Coupling of Unactivated Alkyl Bromides and Aryl Iodides at Room Temperature.

AbstractIn situ generated [Ni0(ethyl crotonate)2·py] complexes are successfully applied for a series of inter‐ and intramolecular reductive cross‐coupling reactions under exceptionally mild conditions.

Alkylboronic Esters from Palladium‐ and Nickel‐Catalyzed Borylation of Primary and Secondary Alkyl Bromides

AbstractPalladium‐ and nickel‐catalyzed cross‐coupling recations of unactivated alkyl bromides with diboron reagents have been developed as practical methods for the synthesis of primary and secondary alkylboronic esters. These reactions extend the concept and utility of Pd‐ and Ni‐catalyzed cross‐coupling of aliphatic electrophiles. They also show different substrate selectivity and ligand dependence as compared to the recently reported Cu‐catalyzed borylation reaction.

Nickel‐Mediated Inter‐ and Intramolecular Reductive Cross‐Coupling of Unactivated Alkyl Bromides and Aryl Iodides at Room Temperature

A nickel-mediated intermolecular reductive cross-coupling reaction of unactivated alkyl bromides and aryl iodides at room temperature has been developed and successfully extended to less explored intramolecular versions and tandem cyclization-intermolecular cross-coupling. Highly stereoselective (or stereospecific) synthesis of linear-fused perhydrofuro[2,3-b]furan (pyran) and spiroketal skeletons allows rapid access to these useful building blocks, which would be potentially valuable in the synthesis of relevant natural products. A rational explanation for the formation of contiguous stereogenic centers is given.

Mild ketone formation via Ni-catalyzed reductive coupling of unactivated alkyl halides with acid anhydrides

Ni-catalyzed ketone formation through mild reductive coupling of a diverse set of unactivated alkyl bromides and iodides with particularly aryl acid anhydrides was successfully developed using zinc as the terminal reductant. These conditions also allow direct coupling of alkyl iodides with aryl acids in the presence of Boc(2)O and MgCl(2).

ChemInform Abstract: Palladium‐ and Nickel‐Catalyzed Direct Alkylation of Azoles with Unactivated Alkyl Bromides and Chlorides.

AbstractTitle reaction tolerates a range of functional groups like ethers, silyl ethers, esters, olefins and acetals.

Palladium‐ and Nickel‐Catalyzed Direct Alkylation of Azoles with Unactivated Alkyl Bromides and Chlorides

Title reaction tolerates a range of functional groups like ethers, silyl ethers, esters, olefins and acetals.

Alkyl–Alkyl Suzuki Cross‐Coupling of Unactivated Secondary Alkyl Chlorides

The first method for achieving alkyl–alkyl Suzuki reactions of unactivated secondary alkyl chlorides has been developed. Carbon–carbon bond formation occurs under mild conditions (at room temperature) with the aid of commercially available catalyst components. This method has proved to be versatile: without modification, it can be applied to Suzuki reactions of secondary and primary alkyl bromides and iodides, as well as primary alkyl chlorides. Mechanistic investigations suggest that oxidative addition is not the turnover-limiting step of the catalytic cycle for unactivated secondary alkyl iodides and bromides, whereas it may be (partially) for chlorides.

Alkyl–Alkyl Suzuki Cross‐Coupling of Unactivated Secondary Alkyl Chlorides

The first method for achieving alkyl–alkyl Suzuki reactions of unactivated secondary alkyl chlorides has been developed. Carbon–carbon bond formation occurs under mild conditions (at room temperature) with the aid of commercially available catalyst components. This method has proved to be versatile: without modification, it can be applied to Suzuki reactions of secondary and primary alkyl bromides and iodides, as well as primary alkyl chlorides. Mechanistic investigations suggest that oxidative addition is not the turnover-limiting step of the catalytic cycle for unactivated secondary alkyl iodides and bromides, whereas it may be (partially) for chlorides.

Salts of Mosher’s thioacid: agents for determining the enantiomer excess of SN2 substrates

Abstract The racemic and the (S)-enantiomer of Mosher’s thioacid, 2-methoxy-2-trifluoromethylphenylacetic thioacid, form air-stable salts with Proton Sponge [1,8-bis(dimethylamino)naphthalene]. These salts are powerful nucleophiles that react cleanly (SN2 inversion) in CDCl3 with optically active alkyl halides ranging in reactivities from unactivated alkyl bromides and iodides to benzylic bromides. The diastereomeric excess (de) of the thioester products indicates the enantiomeric excess (ee) of the starting alkyl halides.

Ligand-assisted nickel-catalysed sp3–sp3 homocoupling of unactivated alkyl bromides and its application to the active template synthesis of rotaxanes

An efficient, mild and operationally simple Ni-catalysed sp3-carbon-to-sp3-carbon homocoupling of unactivated alkyl bromides has been developed and utilised in the active metal template synthesis of an alkyl chain axle [2]rotaxane. The key to the transformation is the use of tridentate nitrogen-donor-atom (terpy or pybox derived) ligands which inhibit competing β-hydride elimination of alkyl-Ni intermediates.

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.