Allylic Grignard Reagents Research Articles

Selective C3-Allylation and Formal [3 + 2]-Annulation of Spiro-Aziridine Oxindoles: Synthesis of 5'-Substituted Spiro[pyrrolidine-3,3'-oxindoles] and Coerulescine.

Brønsted acid- and/or Lewis acid-catalyzed selective C3-allylation and formal [3 + 2]-annulation of spiro-aziridine oxindoles with allylsilanes have been demonstrated to deliver direct access to 3-allyl-3-aminomethyl oxindoles and 5-silyl methyl spiro[pyrrolidine-3,3'-oxindoles], respectively. The acid-catalyzed methods do not provide any stereoselectivity when chiral spiroaziridines are used. However, the reaction of nonracemic sprioaziridines with allyl-Grignard reagent under catalyst-free conditions afforded 3-allyl-3-aminomethyl oxindoles with good stereoselectivity (ee up to 80%). The allylation protocol is utilized for the short synthesis of coerulescine and various 5'-substituted spiro[pyrrolidine-3,3'-oxindoles].

Highly Regioselective Aromatic C-H Allylation of N-(Arylmethyl)sulfonimides with Allyl Grignard Reagents Involving Benzylic C-N Cleavage.

A new pair of reaction partners has been established for the aromatic C-H functionalization of benzyl electrophiles with nucleophiles via palladium-catalyzed benzylic C-N cleavage. A range of N-(1-naphthylmethyl)sulfonimides, N-(2-thienylmethyl)sulfonimides, and N-(2-furanylmethyl)sulfonimides smoothly underwent palladium-catalyzed aromatic C-H allylation with allyl Grignard reagents at room temperature, delivering structurally diverse substituted 1-allylnaphthalenes and 2-allylheteroarenes in moderate to excellent yields with extremely high regioselectivities. Replacing the N-(arylmethyl)sulfonimide with an (arylmethyl)ammonium salt, an arylmethyl chloride, or an arylmethyl phosphate as the benzyl electrophile leads to a dramatic erosion of the regioselectivity.

Tris(dicyclohexylamido) Group 4 Metal Allyl and Phenylacetylide Complexes – Synthesis and Characterization

The synthesis and characterization of organyl complexes derived from group 4 metal dicyclohexylamido complexes (Cy2N)3MCl (Cy: Cyclohexyl, M = Ti, Zr, Hf 1‐M) is presented. The allyl Grignard reagent is used to obtain the corresponding group 4 allyl complexes 2‐M, and lithium phenylacetylide is used to obtain the phenylacetylide complexes 3‐M. The thermal stability of complexes 2‐M and 3‐M is investigated. All complexes are characterized by NMR spectroscopy and single‐crystal X‐ray diffraction. Their molecular structures in solution and in the solid state are discussed.

P-Chiral Monophosphorus Ligands for Asymmetric Copper-Catalyzed Allylic Alkylation

Asymmetric copper-catalyzed allylic alkylation between allyl bromides and alkyl Grignard reagents using a P-chiral monophosphorus ligand is described. A range of terminal olefins bearing tertiary o...

A convenient synthesis of 2-acyl benzothiazoles/thiazoles from benzothiazole/thiazole and N,N'-carbonyldiimidazole activated carboxylic acids

A convenient and efficient strategy for the synthesis of 2-acyl benzothiazoles/thiazoles has been developed. The treatment of benzothiazole/thiazole with allylic Grignard reagents readily generates the corresponding 2-Grignard reagents, which is followed by a reaction with N,N'-carbonyldiimidazole activated carboxylic acids to afford various 2-acyl benzothiazoles/thiazoles products. The synthetic method is applicable to a wide array of carboxylic acids and allows easy access to 2-acyl benzothiazoles/thiazoles with considerable yields under mild reaction conditions.

Mechanistic Insight into Additions of Allylic Grignard Reagents to Carbonyl Compounds.

Allylic Grignard reagents exhibit high reactivity and low selectivity in additions to carbonyl compounds. Additions of allylic Grignard reagents to carbonyl compounds were investigated using prenylmagnesium chloride as a mechanistic probe. When the carbonyl group is relatively unhindered, the addition proceeds through a six-membered transition state with allylic transposition. This process generally occurs with no diastereoselectivity because the reaction rates approach the diffusion limit. With hindered ketones, however, this pathway is disfavored, and the addition proceeds through a transition state resembling that of other Grignard reagents.

Multi-configuration spin-coupled description of organometallic reactions: a comparative study of the addition of RMBr (M = Mg and Zn) to acetone

The large differences in the reactivity between methyl and allyl Grignard reagents and allylzinc bromide in their addition reactions to acetone are theoretically studied. The chemical nature of the transition states is revealed through multi-configuration spin-coupled (MC-SC) calculations. The additional spin-coupled configuration proves to be instrumental in the description of the electronic rearrangements that lead to the reaction. The resulting singly occupied overlapping orbitals indicate clearly that in all cases the transition states present a pronounced carbanion character. The greater reactivity of Grignard reagents is associated with a product-like nature of the transition state, while the zinc reagent presents a reactant-like transition state. Through the analysis of the wave functions around the transition state geometries, we are able to provide unique insights into the electronic inner workings of the alkylation process.

Double Addition of Organometallics to Nitriles: Toward an Access to Tertiary Carbinamines

AbstractAs depicted in many textbooks, the addition of organometallics to nitriles is generally limited to a single addition, providing ketones after acidic hydrolysis. However, the double addition, leading to tertiary carbinamines is also possible, as demonstrated as early as 1939 by the double addition of allyl Grignard reagents to α‐ethoxyacetonitrile. Since this seminal result, and stimulated by the biological importance of the so‐obtained carbinamines, efforts were devoted to expand the scope of the double addition of organometallics to nitriles. This review presents these different approaches which have led to short accesses to tertiary carbinamine derivatives. Particularly interesting is the double addition of different organometallics, which opens the way towards the straightforward asymmetric synthesis of tertiary carbinamines from nitriles.magnified image

ChemInform Abstract: Asymmetric Synthesis of Homoallylic Amines via 1,2‐Addition of Grignard Reagent to Aliphatic N‐Phosphonyl Hemiaminal.

Abstract A general method for asymmetric synthesis of alkylated homoallylic amines was developed via a one-pot three-component reaction of easily available N-phosphonyl amides, aliphatic aldehydes, and allylic Grignard reagents. As anticipated the reaction proceeds through six-membered chelation controlled mechanism, allowing 1,2-nucleophilic addition to directly give chiral homoallylic amines with high yields and excellent diastereoselectivity.

ChemInform Abstract: Cobalt‐Catalyzed Cross‐Coupling of 3‐ and 4‐Iodopiperidines with Grignard Reagents.

AbstractA wide range of functionalized piperidines is efficiently and chemoselectively obtained using various aryl, alkenyl‐, and allyl Grignard reagents.

Asymmetric synthesis of homoallylic amines via 1,2-addition of Grignard reagent to aliphatic N-phosphonyl hemiaminal

A general method for asymmetric synthesis of alkylated homoallylic amines was developed via a one-pot three-component reaction of easily available N-phosphonyl amides, aliphatic aldehydes, and allylic Grignard reagents. As anticipated the reaction proceeds through six-membered chelation controlled mechanism, allowing 1,2-nucleophilic addition to directly give chiral homoallylic amines with high yields and excellent diastereoselectivity.

Synthesis of allyl sulfoxides from allylsilanes via silyl sulfinates

Allylsilanes underwent sila-ene reaction with sulfur dioxide in the presence of Lewis acid catalysts. The obtained Vogel’s silyl sulfinates were found to act as sulfinyl transfer agents in reactions with aryl, heteroaryl, alkyl, and allyl Grignard reagents proceeding with the expulsion of the trialkylsilyloxy group to give allyl sulfoxides in up to 83% yield. The nucleophilic attack of Grignard reagents was accelerated in toluene and in the presence of LiCl or ZnCl2 as Lewis acidic additives. The developed method allows the transformation of allylsilanes into allyl sulfoxides.

Copper-free arylation of 3,3-disubstituted allylic halides with triazene-softened aryl Grignard reagents

A copper-free allylic arylation reaction between 3,3-disubstituted allylic halides and triazene-softened aryl Grignard reagents has been developed. This protocol presents a direct and efficient way to construct both α- or γ-isomers with high regioselectivity under environmentally benign conditions. Various functional groups can be tolerated in the reaction and the products are of high value for multiple synthetic applications. The α- and γ-isomers can be converted to the corresponding 3H-indole and indole derivatives in multigram scale respectively.

Ring-opening of cyclic ethers with carbon–carbon bond formation by Grignard reagents

The ring-opening of cyclic ethers with concomitant C–C bond formation was studied with a number of Grignard reagents. The transformation was performed in a sealed vial by heating to ∼160 °C in an aluminum block or at 180 °C in a microwave oven. Good yields of the product alcohols were obtained with allyl- and benzylmagnesium halides when the ether was tetrahydrofuran or 3,3-dimethyloxetane. Lower yields were obtained with substituted tetrahydrofurans while no ring-opening was observed with tetrahydropyran. Only highly reactive allyl and benzyl Grignard reagents participated in the transformation while no reaction occurred with other alkylmagnesium halides.

Activation of sp3 and sp2 C[sbnd]H bonds of oxygen containing heterocyclic molecules for alkylation and arylation reactions catalyzed by an iron complex

Activation of both sp3 and sp2 CH bonds is reported using an efficient iron(III) complex (1) of a ligand (N2,N6-bis(2,6-diisopropylphenyl)pyridine-2,6-dicarboxamide: L). The iron(III) complex showed catalytic activity of CC coupling reaction of oxygen containing heterocycles, e.g. tetrahydrofuran (THF), with various alkyl, allyl and aryl Grignard reagents under ambient reaction conditions. Complex 1 demonstrated excellent activity and reactions were completed within 30min to 1h. A high turnover frequency (TOF) of 1700h−1 using a low catalyst loading of 0.02mol% was obtained for the reaction. Interestingly, the catalyst was selective in activation of the CH bond adjacent to the oxygen in various oxygen containing heterocyclic molecules to yield 2-substitituted products.

Preparation of Trifluorovinyl Compounds by Lithium Salt-promoted Monoalkylation of Tetrafluoroethene

Abstract Treatment of tetrafluoroethene (TFE) with diethylzinc in the presence of lithium iodide gave 1,1,2-trifluoro-1-butene in moderate yield. In the absence of lithium iodide, however, the nucleophilic addition of diethylzinc to TFE proceeded very slowly to afford ethyl 1,1,2,2-tetrafluorobutylzinc. The addition of lithium iodide to a solution of ethyl-1,1,2,2-tetrafluorobutylzinc resulted in a smooth transformation into 1,1,2-trifluoro-1-butene. In the presence of lithium chloride, the reaction of TFE with benzyl or allyl Grignard reagents afforded the corresponding monosubstituted products in good to excellent yields.

Palladium‐Catalyzed Synthesis and Isolation of Functionalized Allylboronic Acids: Selective, Direct Allylboration of Ketones

Palladium‐Catalyzed Synthesis and Isolation of Functionalized Allylboronic Acids: Selective, Direct Allylboration of Ketones

Synthesis and CO2 Insertion Reactivity of Allyluranium Metallocene Complexes

The U4+ metallocene allyl chloride complexes (C5Me5)2U[η3-CH2C(R)CH2]Cl (R = H, Me) can be synthesized by reaction of (C5Me5)2UCl2 with 1 equiv of the corresponding allyl Grignard reagents, [CH2C(R)CH2]MgCl, in hydrocarbon solvents. Bis(allyl)uranium complexes can also be obtained in this manner using 2 equiv of the corresponding allyl Grignard, and X-ray crystallographic studies reveal the presence of both η3- and η1-allyl ligands: (C5Me5)2U[η3-CH2C(R)CH2][η1-CH2C(R)═CH2]. Sodium amalgam reduction of (C5Me5)2U[η3-CH2C(R)CH2]Cl generates the U3+ metallocene allyl complexes (C5Me5)2U[η3-CH2C(R)CH2]. Carbon dioxide reacts with the U4+ allyl complexes to form the U–C insertion products (C5Me5)2U[κ2O,O′-O2CCH2CH═CH2]2–xClx (x = 0, 1). The dicarboxylate (C5Me5)2U[κ2O,O′-O2CCH2CH═CH2]2, which has a 171.98(5)° O–U–O angle, reacts with Me3SiCl to regenerate (C5Me5)2UCl2 and liberate Me3SiOC(O)CH2CH═CH2.

Synthesis of the key intermediate of ramelteon

Asymmetric conjugated addition of allylcopper reagents derived from an allyl Grignard reagent and CuBr·Me2S to chiral α,β-unsaturated N-acyl oxazolidinones has been achieved. The synthetic procedure was applied to the preparation of the key intermediate of the novel nonbenzodiazepine hypnotic drug, ramelteon.

Substitution of Silanes with Grignard Reagents

A practical substitution reaction of silanes with Grignard reagents in the presence of lithium chloride is described. The reaction rate of allyl and aryl Grignard reagents is greatly accelerated. For many examples, LiCl can be used only in catalytic amounts (5 mol%). Even inherently less reactive alkylsilanes and sterically demanding Grignard reagents give excellent yields.