Vinylic magnesium bromide

A somewhat unusual sequence to generate azepanones 80 involved the intramolecular addition of hydroxylamines to alkynes 76 to form cyclic nitrones 77. A vinyl magnesium bromide addition at low temperatures and a reduction with TiCls followed by N-Boc protection led to the azepane 78. Double bond bromination and subsequent RUO4 oxidation gave the lactam 79. Several further steps allowed the generation of the lactam structure 80 proposed for d,/-aca-cialactam, but the spectral data of the synthetic material differed from that of the natural product (Scheme 16)] [23 a, b]. 

Another domino process, designed by Polt and coworkers [16], deals with the consecutive transformation of an in situ-prepared aldehyde to give 3-amino allylic alcohols 7-31 from 3-amino acids. When the 3-amino acid ester derivative 7-29 is sequentially treated with iBu5Al2H and vinyl magnesium bromide, a 3 2 mixture of the allylic alcohol derivatives 7-30 is obtained in 60% yield, which can be hydrolyzed to give 7-31 (Scheme 7.10). 

The second cycloaddition substrate took to form of 91 (Scheme 1.9b), incorporating a vinyl sulfone dipolarophile. Beginning with cyano ketone 84, which was readily prepared from 1,5-dicyanopentane via a previously reported three-step sequence [45], condensation with thiophenol produced vinyl sulfide 85 in 84 % yield. Vinyl sulfide 85 underwent bromination in acetonitrile to afford bromo-vinyl sulfide 86 (86 %), which was then treated with isopropylmagnesium chloride [46] to effect metal-halogen exchange affording an intermediate vinyl magnesium bromide species. Subsequent alkylation with Mel in the presence of catalytic CuCN provided the alkylated vinyl sulfide 87 in 93 % yield. The nitrile within vinyl... 

Photocycloaddition of allene to cyclohexenone (341) gave the (3,y-enone (342), which reacted with vinyl magnesium bromide to produce the tertiary alcohol (343) in 79% yield. When the compound (343) was treated with KH and 18-crown-6 in THF at room temperature for two hours and quenched with aq. NH4C1, the cyclobutene (344) was obtained. The thermal ring opening of the cyclobutene (344) proceeded in toluene in a sealed-tube at 180 °C for twelve hours to give a readily separable 5 1 mixture of the civ-olefin (345), and the trans-olefin (346) respectively in 95 % yield. Moreover, (345) could be converted to a mixture of (346) and (345) in the ratio of 10 1 by irradiation. The compounds (345) and (346) possess the skeleton of the germacranes (347), (348) and (349) 122). 

Another recent example of a Michael addition of organometallic reagents to sugar nitroolefins consists of the addition of vinyl magnesium bromide to nitroolefin 83, that afforded nitro sugar 84 (Scheme 27).64... 

Vinylic tellurides (generalprocedure) Elemental Te (0.6 g, 5.0 mmol) is added to a solution of the vinylic magnesium bromide (5.5 mmol) in THE (10 mL) under reflux and N2 atmosphere, and the reflux maintained for 20 min. The mixture is allowed to reach room temperature and then treated with n-butyl bromide (0.7 g, 5.0 mmol). After stirring for 10 min, the reaction mixture is cooled at 0°C, treated dropwise with saturated aqueous NH4CI, extracted with ether, dried (MgS04) and then evaporated. Kiigelrohr distillation of the residue under vacuum gives the vinyl alkyl tellurides as yellow liquids. 

Divinylic ditellurides (generalprocedure) Elemental Te (12.7 g, 100 mmol) is added at once to a stirred solution of the vinylic magnesium bromide (0.11 mol) in THE (150 mL) under N2. The mixture is refluxed for 30 min with stirring, allowed to reach room temperature, then stirred for 1 h in the presence of air (by opening the apparatus). Deposition of some Te is observed during the oxidation process. The mixture is treated with brine. 

As early as the 1960s, some syntheses based on the addition of nucleophilic reagents (vinyl magnesium bromide, HCN, isonitrile) on A-acyl trifluoroacetaldi-mines (fluoral imine) have appeared. The acidic function is further introduced by an appropriate oxidation or hydrolysis. These approaches have allowed preparation of higher fluoroalkylated homologues of trifluoroalanine and of nonracemic trifluor-oalanines (vide infra). However, preparation of the acyl imine of fluoral is rather... 

Alternatively, vinylation can be achieved in useful yields using readily available vinyl magnesium bromide. The allylic tertiary alcohol resulting from this condensation on a ketosugar can be further elaborated by suitable modification of the vinylic group. 

This particular reaction has been reported recently by Lukacs in the context of complex molecules synthesis by Diels-Alder cycloaddition [19]. A typical example is given in the experimental section. Note that the reaction of 5 with vinyl magnesium bromide gave a mixture of 4 and 6 because of epimerization of the axial methyl group at C-2 owing to the basicity of the reagents [20]. 

The silicon-metal doubly bonded compounds can further react to yield desired derivatives. Recently, vinyl magnesium bromide was reported to react with chloro complexes containing chromium or iron double bonds to silicon, to yield the l-metalla-2-sila-l,3-diene compounds (115, equation 34), which can potentially be used to functionalize silicon polymers in a desired fashion121. 

A general methodology for the construction of quaternary carbon atoms at the carbonyl carbon of ketones has been successfully exploited for the facile synthesis of ( )-lycoramine (299) (Scheme 30) (165). Thus, the O-allylated o-vanillin 322 was allowed to react with vinyl magnesium bromide followed by Jones oxidation, and the acid-catalyzed addition of benzyl IV-methylcarbamate to the intermediate a,(3-unsaturated ketone furnished 323. Wadsworth-Emmons olefination of 323 with the anion derived from diethyl[(benzylideneami-no)methyl]phosphonate (BAMP) provided the 2-azadiene 324. The subsequent regioselective addition of n-butyllithium to 324 delivered a metalloenamine that suffered alkylation with 2-(2-bromoethyl)-2-methyl-l,3-dioxolane to give, after acid-catalyzed hydrolysis of the imine and ketal moieties, the 8-keto aldehyde 325. Base-catalyzed cycloaldolization and dehydration of 325 then provided the 4,4-disubstituted cyclohexenone 326. The entire sequence of reactions involved in the conversion of 323 to 326 proceeded in very good overall yield and in one pot. 

Methyl 2-(2-iodophenyl)propanoate Tetrabutylammonium chloride Diethyl 1,1-cyclopropanedicarboxylate Vinyl magnesium bromide Methyl magnesium chloride Borane-tetrahydrofuran complex Diisopropylethylamine Methanesulfonyl chloride... 

Cool both solutions to -25°C, transfer the allenyl zinc bromide solution to the stirred vinyl magnesium bromide using a cannula, and stir the reaction mixture at -20°C for 4 h. The quantitative formation of the adduct is checked by GC. 

The use of RCM in the synthesis of 3,4-carbocyclic indoles was reported by Perez-Castells and co-workers as is exemplified in Scheme 29 <02T5407>. Vinyl indole 49 was quatemized with BnBr and quaternary salt underwent smooth addition of vinyl magnesium bromide to give the indole diene 50. RCM was accomplished with the MC2 in good yields. 

Tetravinyl tellurium was prepared from tellurium tetrachloride and vinyl magnesium bromide in tetrahydrofuran6. 

The high reactivity of compounds containing an episulfonium moiety has been used in an one-carbon ring expansion step [42]. This method is explained at the system shown in Scheme II/8. 1-Vinylcyclopentanol is easily prepared from cyclopentanone (11/50) and vinyl magnesium bromide. The silylation of the alcohols was carried out with re/7-butyldimethylsilyloxytriflate (TBDMSOTf). Using trimethylsilylethers instead of TBDMSO-derivatives side reactions are... 

The combined action of lithium in liquid ammonia and carbon dioxide upon androst-4-en-3-one led to a synthesis of the /3-keto-ester (189), after esterification of the intermediate acid the reaction is one of reductive methoxycarbonyla-tion.82 Alkylation of the keto-ester (189) afforded a separable mixture of the 4/3-methyl steroid (190) as the major product (55%) and the corresponding 4a-methyl epimer. Reduction of the steroid (190) led to 4a-hydroxymethyl-4/3-methyl-5a-androstan-3/3-ol. Finally in this section, it has been noted that vinyl-magnesium bromide effects 1,4-addition to the a(3-unsaturated ketone 17/3-hydroxy-5a-androst-l-en-3-one to yield la-vinyl-5a-androstan-3-on-17/3-ol, which could be further reduced to the la-ethyl-3-ketone.83... 

In another work, the POSS-24C1 dendrimer was found to react with vinyl-magnesium bromide to give a 24-vinyl dendrimer [142]. However, POSS-24C1 also reacted with allylmagnesium bromide to give a 24-allyl dendrimer. 

In a side-chain containing a double-bond 3 to the oxirane, double-bond migration has also been observed. The effects of the solvent and the reagent have been examined in the reaction of vinyl-magnesium bromide and phenyloxirane. Acetylenic oxirane gives a complicated mixture of products with a Grignard reagent, but the Cu halide-catalyzed reaction leads to an allene alcohol (Eq. 

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