One-step three-component coupling of aromatic organozinc reagents, secondary amines, and aromatic aldehydes into functionalized diarylmethylamines

Numerous functionalized diarylmethylamines have been synthesized in high yield according to a one-step three-component coupling between an aromatic organozinc reagent, a secondary amine, and an aromatic aldehyde. Both organozinc species and aldehyde can bear a functional group and either aromatic or non-aromatic amines can be used in this versatile procedure.     

New progress in the cobalt-catalysed synthesis of aromatic organozinc compounds by reduction of aromatic halides by zinc dust

The experimental conditions of the cobalt-catalysed synthesis of aromatic organozinc species from the corresponding bromides have been optimised. The preparation of numerous aromatic organozinc reagents under these optimised conditions is reported, with yields between 67 and 99%.     

Use of functionalized aromatic organozinc reagents in the three-component Mannich-type synthesis of diarylmethylamines

Efficient syntheses of functionalized diarylmethylamines have been realized according to a one-step three-component coupling between an aromatic aldehyde, a secondary amine and an aromatic organozinc reagent. Phenyl rings can be substituted by functional groups and either aromatic or non-aromatic amines can be used in this process.     

Redox-active ligand-mediated oxidative addition and reductive elimination at square planar cobalt(III): multielectron reactions for cross-coupling

Square planar cobalt(III) complexes with redox-active amidophenolate ligands are strong nucleophiles that react with alkyl halides, including CH(2)Cl(2), under gentle conditions to generate stable square pyramidal alkylcobalt(III) complexes. The net electrophilic addition reactions formally require 2e(-) oxidation of the metal fragment, but there is no change in metal oxidation state because the reaction proceeds with 1e(-) oxidation of each amidophenolate ligand. Although the four-coordinate complexes are very strong nucleophiles, they are mild outer-sphere reductants. Accordingly, addition of alkyl- or phenylzinc halides to the five-coordinate organometallic complexes regenerates the square planar starting materials and extrudes C-C coupling products. The net 2e(-) reductive elimination reaction also occurs without a oxidation state change at the cobalt(III) center. Together these reactions comprise a complete, well-defined cycle for cobalt Negishi-like cross-coupling of alkyl halides with organozinc reagents.     

Straightforward three-component synthesis of diarylmethylpiperazines and 1,2-diarylethylpiperazines

Several functionalized diarylmethylpiperazines and 1,2-diarylethylpiperazines have been synthesized in moderate to high yield according to a one-step three-component coupling between an aromatic or a benzylic organozinc reagent, a piperazine derivative, and an aromatic aldehyde. The procedure can be extended to the synthesis of benzylpiperazine derivatives or β-arylethylpiperazines toward the use of paraformaldehyde or aliphatic aldehydes.     

New efficient preparation of arylzinc compounds from aryl halides using cobalt catalysis and sacrificial anode process

Electroreduction of aryl-chlorides or -bromides in an electrochemical cell fitted with a sacrificial zinc anode and in the presence of cobalt halide associated with pyridine as ligand in DMF or acetonitrile as solvent affords the corresponding organozinc species in good yields.     

Catalytic Asymmetric Ring-Opening Reactions of Unstrained Heterocycles Using Cobalt Vinylidenes

Cobalt catalysts promote highly enantioselective ring-opening reactions of 2,5-dihydrofurans using vinylidenes. The products are acyclic organozinc compounds that can be functionalized with an electrophile. The proposed mechanism involves the generation of a cobalt vinylidene species that adds to the alkene by a [2+2]-cycloaddition pathway. Ring-opening then occurs via outer-sphere β-O elimination assisted by coordination of a ZnX₂ Lewis acid to the alkoxide leaving group. DFT models reveal that competing inner-sphere syn β-H and β-O elimination pathways are suppressed by the geometric constraints of the metallacycle intermediate. These models rationalize the observed stereochemical outcome of the reaction.     

Pd(II)催化下苄基溴化锌或烯丙基碘化锌与芳香醛的加成反应

在[PdCl2(PPh3)2]催化下,有机卤化锌试剂与芳香醛顺利地发生反应得到了较高产率的1,2-加成产物.此方法避免了CuCN/2LiCl的使用,为通过有机卤化锌试剂合成芳基取代的仲醇类化合物提供了一条简便的途径.     

Investigations on the Suzuki-Miyaura and Negishi couplings with alkenyl phosphates: application to the synthesis of 1,1-disubstituted alkenes

The development of versatile Suzuki-Miyaura and Negishi cross-couplings with nonactivated alkenyl phosphates and aromatic boronic acids or organozinc reagents was achieved in acceptable to good yields. A series of 1,1-disubstituted alkenes were synthesized using a combination of either Ni(COD)2/Cy3P/K3PO4 or Pd2dba3/DPPF in THF. When working with alkenyl electrophiles in metal-catalyzed cross-couplings, this method lends itself as a less costly and more stable alternative to the corresponding triflate or nonaflate derivatives. In addition, initial studies are presented regarding an efficient 1,2-migration under Negishi coupling conditions.     

A concise three-component synthesis of α-amino esters derived from phenylglycine and phenylalanine

α-Amino esters have been synthesized using a straightforward three-component reaction among preformed or in situ-generated aromatic or benzylic organozinc reagents, primary or secondary amines and ethyl glyoxylate. The procedure, which is characterized by its simplicity, allows the concise synthesis of phenylglycine and phenylalanine derivatives.     

Nickel(II)-catalyzed carbon-carbon bond formation reaction of functionalized organozinc reagents with aromatic aldehydes

In the presence of a silylating reagent and catalytic amount of Ni(acac)₂, organozinc halides reacted with aromatic aldehydes to give the corresponding dialkylation products in good to excellent yields under mild conditions.     

Aromatic organozinc reagents as nucleophiles in the α-arylation of piperidine and tetrahydropyran

The arylation at the α-position of piperidine derivatives is achieved in good yield using aromatic organozinc reagents and either 2-methoxylated or α-cyanated piperidine. Oxygen-containing heterocycles such as 2-methoxy-tetrahydropyran reacts in a same manner to yield efficiently 2-arylated tetrahydropyran.     

New B-substituted derivatives of m-carborane, p-carborane, and cobalt bis(1,2-dicarbollide) anion

The Pd-catalyzed cross-coupling reactions of B-I bond in m- and p-carboranes and cobalt bis(1,2-dicarbollide) anion with organomagnesium and organozinc compounds were studied. Carboranyl derivatives of furan, thiophene, indole, pyridine and quinoline were synthesized. 2-Pyridylethynyl and 3-quinolylethynyl derivatives of p-carborane were prepared by Pd-catalyzed cross-coupling reactions using corresponding alkynes or their magnesium derivatives.     

Decarboxylative Negishi Coupling of Redox‐Active Aliphatic Esters by Cobalt Catalysis

A cobalt‐catalyzed decarboxylative Negishi coupling reaction of redox‐active aliphatic esters with organozinc reagents was developed. The method enabled efficient alkyl–aryl, alkyl–alkenyl, and alkyl–alkynyl coupling reactions under mild reaction conditions with no external ligand or additive needed. The success of an in situ activation protocol and the facile synthesis of the drug molecule (±)‐preclamol highlight the synthetic potential of this method. Mechanistic studies indicated that a radical mechanism is involved.     

Combined application of organozinc chemistry and one-pot hydroboration-Suzuki coupling to the synthesis of amino acids

Hydroboration using 9-BBN-H of the protected enantiomerically pure but-3-enylglycine derivative 11, prepared by copper-catalysed allylation of the serine-derived organozinc reagent 1, followed by Suzuki coupling of the derived borane with a variety of aromatic halides, 2-bromopyridine and 2-bromopropene gives the protected amino acids 14a-l and 15. This method augments our previous methods for the synthesis of phenylalanine homologues.     

Stabilization of CoI by ZnII in pure acetonitrile and its reaction with aryl halides

The study of the electrochemical behavior of cobalt(II) bromide (CoBr(2)) in pure acetonitrile allowed us to demonstrate that Co(2+) is the catalyst precursor involved in the electrochemical and chemical conversions of arylhalides, ArX, to arylzinc compounds in that solvent. The reduction of Co(2+) leads to the Co(+) species, which disproportionates too rapidly to react further with aryl halides. However, the presence of zinc(II) bromide allows us to stabilize the electrogenerated cobalt(I) and to observe it on the timescale of slow cyclic voltammetry. Under such conditions, the Co(I) species has time to react with aryl halides and produce [Co(III)ArX](+) complexes that are reduced into [Co(II)ArX] by a single electron uptake at the same potential at which Co(2+) is reduced. Rate constants for the oxidative addition of ArX to Co(I) have been determined for various aryl halides and compared to the values obtained in an acetonitrile (ACN)/pyridine (9:1, v/v) mixture. It is shown that Co(I) is stabilized more by ZnBr(2) than by pyridine. A transmetallation reaction between [Co(II)ArX] and ZnBr(2) has also been observed. We finally propose a mechanism for the cobalt-catalyzed electrochemical conversion of aryl bromides into organozinc species in pure acetonitrile.     

Pd(II)催化下苄基溴化锌或烯丙基碘化锌与芳香醛的加成反应

在[PdCl₂(PPh₃)₂]催化下, 有机卤化锌试剂与芳香醛顺利地发生反应得到了较高产率的1,2-加成产物. 此方法避免了CuCN/2LiCl的使用, 为通过有机卤化锌试剂合成芳基取代的仲醇类化合物提供了一条简便的途径.     

Microwave-Assisted Olefination Reaction of Alkylzinc with Aromatic Aldehyde Catalyzed by Nickel Complex

Carbon-carbon double bond-forming reactions have always been great importance in organic synthesis. Manymethods have been described for C =C bond formation. We[1] have reported the new method of C =C bond formation of nickel catalyzed organozinc with aromatic aldehydes in the presence of Me3SiC1.     

Influence du cérium dans l'hydrogénation sélective du cinnamaldéhyde en présence de catalyseurs cobalt supportés

The study of the cinnamaldehyde hydrogenation over supported cobalt catalysts shows that the addition of cerium to cobalt increases the selectivity to unsaturated alcohol without decrease of the activity. Moreover the support has an important effect over the catalytic properties of the mixed cobalt-cerium system; active carbons clearly lead to the most active catalysts. If the calcination step does not modify the catalytic properties, the reduction step has a decisive effect, i.e. after a reduction with hydrogen at low temperature, a selectivity to unsaturated alcohol of 95 % is obtained at a conversion of 90 %. The preparation method, especially the order of addition of the elements (cobalt and cerium) to the support (C_L2S) also has an important effect, both on the activity and the selectivity. The first step of ceria dispersion on the support leads to the most efficient catalyst. The study of the catalysts reducibility and the electron microscopy micrographs show that in that case, the cobalt and cerium dispersion are much more important than that observed with another preparation.     

Radical-polar crossover domino reactions involving organozinc reagents and β-(allyloxy)-enoates

Organozinc reagents (organozinc halides, diorganozincs and mixed copper-zinc reagents) react with β-(allyloxy)-enoates via a radical-polar crossover process to afford substituted furans in one single synthetic step following a domino reaction involving Michael addition and carbocyclisation. Reversal of diastereoselectivity can be obtained varying the organometallic and/or the reaction conditions.