Vinyl Grignard Reagents Research Articles

Studies Directed toward the Synthesis of (+)-Sesbanimide A: Construction of the AB-Ring System (A Formal Total Synthesis)

Complete details of a study leading to the asymmetric synthesis of the AB-ring system of (+)-sesbanimide A (1), a potent cytotoxic agent belonging to the class of sesbania alkaloids, are described. Key features of the synthesis include (a) the stereoselective introduction of the C8 and C9 hydroxyl groups through the use of a diastereoselective catalytic osmylation of enantiomerically enriched α-alkoxy allylsilanes and (b) a chelation-controlled nucleophilic addition of a vinyl Grignard reagent to a syn α-alkoxy β-(silyloxy) aldehyde for the introduction of the C7 stereocenter required for assembly of the B-ring

Stereoselective reactions of lithio-vinylsulf oxides with aldehydes

A series of homochiral vinyl sulfoxides—synthesised by treating vinyl Grignard reagents with homochiral menthyl toluene-p-sulfinate or sulfinyl oxazolidinones 8a and 9a–were deprotonated with LDA and allowed to react with acetaldehyde, isobutyraldehyde, and trimethylacetaldehyde to give β-hydroxy sulfoxides with moderate diastereoselectivity. The sulfoxide 1 gave the best selectivity with the larger aldehyde. The same diastereoselectivity, within experimental error, is observed in the reactions with trimethylacetaldehyde of both E-1 and Z-1 giving 85:15 and 84:16 mixtures of 2c and 3c respectively; evidently, the geometry of the vinyl group does not affect the selectivity.

Synthesis of Vinyl and β-Phthalimido Ketones

Abstract Vinyl ketones are prepared by reaction of an aldehyde with a vinyl Grignard reagent followed by a Swern oxidation. β-Phthalimido ketones are then obtained by 1,4-addition of phthalimide.

Reactivity of nitro- and nitroso-arenes with vinyl grignard reagents: synthesis of 2-(trimethylsilyl)indoles

The reaction of nitrosoarenes and 1 -(trimethylsilyl)vinylmagnesium bromide in dibutyl ether represents a useful tool for the synthesis of 2-(trimethylsilyl)indoles by cyclisation of benzene derivatives. The use of more common ethers as the solvent leads to large amounts of azo and azoxy derivatives. Conversely, the reaction of nitroarenes and 1-(trimethylsilyl)vinylmagnesium bromide gives conjugate addition products. The reasons for this behaviour are discussed.

Mechanistic studies on the reaction of nitro- and nitrosoarenes with vinyl Grignard reagents

The reaction of ortho-substituted nitrobenzenes with 3 mol vinylmagnesium halides gives mainly 7-substituted indoles together with minor amounts of the aniline from complete reduction of the nitroarene. Under the same experimental conditions, para-substituted nitrobenzenes essentially lead to the corresponding anilines, with indoles being recovered in very low yield. Nitrosoarenes react with 2 mol Grignard reagent to give almost the same product distribution. An accurate analysis of the stoichiometry of the reaction established that in the first stage of the reaction nitroarenes are attacked at the oxygen atoms and are reduced to nitrosoarenes via enolate elimination. The nitroso derivative can undergo a 1,2-addition to give an N-aryl-N-vinylhydroxylamino magnesium salt. Hydrolysis of this intermediate affords hydroxylamine and the carbonyl derivative corresponding to the vinyl Grignard reagent, as proved by the reaction of nitroarenes with 2 mol Grignard reagent. In the presence of an excess of vinyl magnesium halide, a complete reduction to vinylaniline derivatives, which hydrolyse to aniline, occurs. The effect of the bulkiness of the substituent both in the nitroarene and in the Grignard reagent, the orientation of alkylation and the relative reaction rates of indole and aniline formation suggest that indoles arise via a completely different route: i.e. an inverse 1,2-addition to the NO double bond. The N-aryl-O-vinylhydroxylamino magnesium salt intermediate can undergo a [3,3]-sigmatropic rearrangement followed by a rapid ring closure. The third mole of Grignard reagent acts as a base on this bicyclic intermediate, re-aromatizing the six-membered ring. Elimination of water ultimately leads to the indole.

ＦＫ５０６およびＦＫＢＰプローブ試薬，（Ｃ８， Ｃ９‐｀１３´Ｃ２）‐ＦＫ５０６の全合成 イムノフィリンと，その免疫抑制剤リガンドの化学と生物学

Asymmetric syntheses of FK 506 and (C8, C9-13C2) -FK 506 are reported. The latter compound was designed to facilitate an investigation of the interactions between FK 506 and its receptor, the recently discovered immunophilin, FKBP. The synthesis involved the preparation of intermediates 7-9 in nonracemic forms. The key coupling reactions included a Cram-selective addition of the vinyl Grignard reagent derived from bromide 9 to aldehyde 8 and the addition of the lithioanion of phosphonamide 7 to aldehyde 43, followed by thermal elimination. Dithiane 44 was then hydrolyzed, and glycolic ester 6 (or 6*) was added via an aldol reaction that allowed the introduction of 13C labels at C8 and C9. Elaboration to FK 506 proceeded via a Mukaiyama lactamization reaction and a selective deprotection/oxidation sequence, the efficiency of which was critically dependent upon the order of protecting group removal.13C labeled FK 506 (2) -FKBP drug protein complex was examined by 13C NMR ; the experiments did not show an enzyme bound tetrahedral intermediate, but revealed a noncovalent, fully reversible interaction of the drug with its receptor.Also delineated are the recent researches aiming at understanding the structural basis for the molecular recognition of immunosuppressants by immunophilins and the biological consequences of their interactions.

Stereoselective introduction of a carboxy group into a santonin derivative for higher terpene lactone synthesis

While conjugate addition of potassium cyanide or diethylaluminium cyanide to the enone (5) yielded the β-cyano addition product (6), reaction of the same substrate with a vinyl Grignard reagent in the presence of copper(I) iodide gave rise to formation of the stereochemically reversed addition product (10). The products were transformed to the carboxylic acid (8a) and the epimeric acid (13a), respectively.

ChemInform Abstract: The Reaction of Vinyl Grignard Reagents with 2‐Substituted Nitroarenes: A New Approach to the Synthesis of 7‐Substituted Indoles.

AbstractVarious nitroarenes are treated with vinylmagnesium bromide (II) to undergo reductive cyclization, forming indoles, e.g. (III).

ChemInform Abstract: Rhodium‐Catalyzed Isomerization of 1,3‐Diene Monoepoxides to α,β‐Unsaturated Carbonyl Compounds.

AbstractThe α‐bromo ketones (I) react with the vinyl Grignard reagent (II) to give the vinyloxiranes (III) which rearrange in the presence of a rhodium catalyst, forming the unsaturated ketones (IV).

Substitution reactions of 2-benzenesulphonyl cyclic ethers with carbon nucleophiles

Direct substitution of 2-benzenesulphonyl cyclic ethers was studied using a variety of carbon nucleophiles. These nucleophiles included organozinc reagents (derived from aryl, vinyl and alkynyl Grignard reagents) or silyl enol ethers, silyl ketene acetals, allylsilanes and trimethylsilylcyanide in the presence of aluminum chloride. A general selectivity for the formation of the trans-product was observed using 6-subsitituted sulphones.

The reaction of vinyl grignard reagents with 2-substituted nitroarenes: A new approach to the synthesis of 7-substituted indoles

The reaction of three moles of vinylmagnesium bromide with one mole of nitroarene leads to the formation of indoles after aqueous work up of the mixture. Good yields are obtained with ortho-substituted nitroarenes.

A One-Pot Procedure for Attaching two Differentiated Carbon Side Chains to Adjacent Carbons of an Arene Ring

Abstract Treatment of o-bromoiodobenzene successiveiy with a vinyl Grignard reagent (2+ equivatents) and an allylic hatide (1+ equivalent) gives a good yield of arene containing adjacent vinyl and allyl sidechains. In recent papers we showed that vinyl or vinylsilyl Grignard reagents can be used to generate and trap arynes from polyhaloarenes.2 The reaction, illustrated below for o-bromoiodobenzene, involves three steps: Grignard exchange, aryne formation, and nucteophilic addition of a second equivalent of Grignard reagent to the aryne.

Divinyl ditellurides: synthesis and reactivity

Reaction of vinyl Grignard reagents with elemental tellurium followed by air oxidation furnished divinyl ditellurides [(CH 2=CHTe) 2, (CH 2+C(CH 3)Te) 2, (CH 3CH=CHTe) 2, (C 6H 5CH=CHTe) 2] in 58–68% yield. When the intermediate bromomagnesium ethenetellurolates were hydrolysed prior to the oxidation, a complex mixture of products was obtained. Divinyl ditellurides were reduced with sodium borohydride in ethanol to give dialkyl ditellurides (CH 3CH 2Te) 2, [(CH 3) 2CHTe] 2, (CH 3CH 2Ch 2Te) 2 in 67–83% yield. When the reduction of di(propen-2-yl) ditelluride was performed in the presence of phenylacetylene, the isopropyl-2-phenylethynyl telluride was obtained in 86% yield, indicating that an alkanetellurolate is an intermediate in this reaction. Contrary to this result, reduction of divinyl ditellurides with lithium aluminum hydride in tetrahydrofuran or with lithium in liquid ammonia furnished ethenetellurolate anions, which on reaction with alkyl halides afforded vinyl alkyl tellurides [C 4H 9TeCH=CH 2, C 4H 9Te(CH 3)C=CH 2, C 4H 9TeCh=CHCH 3] in 63–85% yield.

Transition–metal mediated asymmetric synthesis. Part 6. Organometallic approaches to the enantiomer synthesis of tridachione: a role for planar chirality in synthesis design

Two series of complexes which contain planar chirality have been examined as intermediates for the synthesis of tridachione. Alkylation of tricarbonyl(η5-2-methoxy-3,5-dimethylcyclohexadienyl)iron(1+) hexafluorophosphate(1–) with trimethylsilyl cyanide and reaction of the nitrile product with ethyl-lithium afforded an acyl-substituted intermediate for the synthesis of tridachione. Complexation of 1-methoxy-2,4-dimethylbenzene by Mn(CO)3+ gave a complex that was alkylated by vinyl Grignard reagents at the correct position to introduce the 1-methylpropenyl group in tridachione. Methylmagnesium bromide gave predominantly an unexpected regioisomer. These products were converted into Mn(CO)2NO+ dienyl complexes. The influence of the use of planar chirality on the design of synthetic strategies is discussed.

Synthèse de complexes σ-vinyliques de ferriporphyrines et leur oxydation en N-vinyl-porphyrines: Rétention de la stéréochimie de la double liaison

Various σ-vinyl( meso-tetraarylporphyrin)iron(III) complexes have been obtained by reaction of the vinylic Grignard reagents R 1R 2CCHMgBr (R 1  R 2  C 6H 5, R 1  R 2  CH 3, R 1  H, R 2 n-C 4H 9 and R 1  n-C 4H 9, R 2  H) with Fe III( meso-tetraarylporphyrin)(ClO 4 complexes. The N-vinyl porphyrins derived from these σ-vinyl(porphyrin)iron(III) complexes by monoelectronic FeCl 3 oxidation were isolated and completely characterized. This two-step route from vinylic Grignard reagents to the corresponding N-vinylporphyrins occurs with retention of the stereochemistry of the double bond of the starting organometallic compound. It is highly probable that each of the two steps involved occurs with retention of this stereochemistry.

ChemInform Abstract: Reversal of Regiocontrol in the Alkylation of an Arene π‐Complex.

AbstractCompound (I) was alkylated with the vinyl Grignard reagents (IIb) and (IIc) at C‐5 position, but when the methyl Grignard reagent (IIa) was used, the reaction occurred predominantly at the more hindered C‐3 position.

ChemInform Abstract: 3‐Alkoxypropenals as Precursors in the Synthesis of Conjugated and Semiconjugated Polyenes: Methy1‐Substituted Octa‐ and Nona‐tetraenes.

AbstractThe vinylic or allylic Grignard reagents (I) or (IV) react with the ethoxypropenals (II) to produce the conjugated and semiconjugated dienals (III) or (V).

ChemInform Abstract: cis‐ and trans‐Opening of Oxirane by Vinyl Grignard Reagents.

AbstractDie Ringöffung des Oxirans (I) mit Vinylmagnesiumbromid (II) in Gegenwart von 98%igem Kupfer(I)‐iodid liefert überraschenderweise ein Gemisch aus dem trans‐ (III) und dem cis‐Alkohol (IV).

Reversal of regiocontrol in the alkylation of an arene π-complex

Tricarbonyl(η 6-1-methoxy-2,4-dimethylbenzene)manganese(1+) hexafluorophosphate(1−) was preferentially alkylated by vinyl Grignard reagents at C(5), When methymagnesium bromide was used, however, reaction occurred predominantly at C(3), the more hindered of the two sites meta to the methoxy substituent.

3-Alkoxypropenals as precursors in the synthesis of conjugated and semiconjugated polyenes: methyl-substituted octa- and nona-tetraenes

Vinylic and allylic Grignard reagents react cleanly and rapidly with 3-ethoxypropenal and 2-methyl-3-ethoxypropenal to produce excellent yields of conjugated and semiconjugated dienals useful in the subsequent preparation of substituted octa- and nona-trienols. Variations in the substitution pattern allow the preparation and isolation of 2-, 3-, and 4-methylocta-1,3,5,7-tetraenes, nona-1,3,5,8-tetraene, and 5-methylnona-1,3,5,8-tetraene in good yield from the octa- and nona-trienols. Thus oxopropenylation of unsaturated Grignard reagents allows the straightforward preparation of numerous previously unknown and uncharacterized polyenes.