Allylation indium bromide

The most widely used preparative method of allylindium(m) or propargylindium(lll) compounds is the oxidative addition of metallic indium or indium(l) halides to allylic or propargyl substrates.4 26 27 Allylic bromides and iodides serve as good allylic sources without any other activation. In the case of allylic chlorides, a proper additive such as lithium iodide is required to promote the oxidative addition. Allylic indium compounds prepared by oxidative addition of metallic indium are considered to exist as the sesquihalide structure (allyl jImXj), which has been... 

When reacted with allyl/propargyl bromide in the presence of indium and sodium iodide, isatins undergo efficient allylation/propargylation to afford the corresponding 3-substituted 3-hydroxy-oxindoles (Scheme 50).206 Indium-mediated Barbier reaction of ninhydrin with benzyl bromide in DMF gives 45 and O-benzylated compound 46. Similarly, the reaction of isatin with allyl bromide affords 47 and 48.207... 

Chiral allylic indium reagents and achiral aldehydes. Chiral indium reagents have been generated by the oxidative metallation of allylic bromides, which bear remote stereogenic subunits. For example, the 1,4-asymmetric induction in the indium-mediated coupling of allyl bromides 298 with benzaldehyde affords the syn-adducts as the major products (Table 10-35) [199]. The stereoselectivity of the reaction improves with more sterically encumbered allyl bromides. 

The allylation of aldehydes with allyhc bromide in water, in the presence of stoichiometric amounts of InClj and Sn, proceeds cleanly to give the corresponding anti y-adducts predominantly (Scheme 8.16) [7b[. It has been postulated that transmetalation from allylic stannane to allyllic indium via an S, 2 process occurs during this reaction the high anti selectivity can be explained in terms of a sixmembered ring transition state. 

Addition of Allyl Indium on Unprotected Sugars Schmid and Whitesides [47] described an extension by three carbon atoms of unprotected carbohydrates by a tin-or indium-mediated reaction with allyl bromide. This reaction was exploited in the synthesis of D-giycero-D-galttcto-heptose 81 starting from D-arabinose (Scheme 2.21) [4 ]. 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

Normally, the addition of C-nucleophiles to chiral a-alkoxyaldehydes in organic solvents is opposite to Cram s rule (Scheme 8.15). The anti-Cram selectivity has been rationalized on the basis of chelation control.142 The same anti preference was observed in the reactions of a-alkoxyaldehydes with allyl bromide/indium in water.143 However, for the allylation of a-hydroxyaldehydes with allyl bromide/indium, the syn isomer is the major product. The syn selectivity can be as high as 10 1 syn anti) in the reaction of arabinose. It is argued that in this case, the allylindium intermediate coordinates with both the hydroxy and the carbonyl function leading to the syn adduct. 

The same coordination is used to account for the observed anti preference in the allylation of (t-hydroxybutanal with allyl bromide/indium in water (Scheme 8.16). The intermediate leads to the anti product. In support of the intramolecular chelation model, it is found that if the hydroxy group is converted to the corresponding benzyl or t-butyldimethylsilyl ether, the reaction is not stereoselective at all and gives nearly equal amounts of syn and anti products. 

A new method has been developed for the synthesis of ( )-3-methyl Baylis-Hillman-type adducts with high E/Z (>93%) selectivity in modest to good yields. The process consists of two steps an indium-mediated allylation reaction and a simple base-catalyzed isomerization step (Eq. 8.61). Various aldehydes were allylated with allyl bromides using indium under very mild conditions in aqueous media and thus converted to the Baylis-Hillman-type adducts.150... 

C-branched sugars or C-oligosaccharides are obtainable through indium-promoted Barbier-type allylations in aqueous media.151 Indium-mediated allylation of a-chlorocarbonyl compounds with various allyl bromides in aqueous media gave the corresponding homoallylic chlorohydrins, which could be transformed into the corresponding epoxides in the presence of a base (Eq. 8.62).152... 

Propargylation (allylation) of diphenylmethyl 6-oxopenicillanate and 7-oxocephalosporanate was accomplished by reacting the corresponding bromides in the presence of indium or zinc in moderate yields in aqueous conditions.206... 

It was reported that the indium-mediated Michael addition of allyl bromide to l,l-dicyano-2-arylethenes proceeded well in an aqueous medium.55 Similarly, cyclopentadienylindium(I) was reported to add in... 

Iminium ions, generated in aqueous solution from secondary amines and formaldehyde, undergo a Barbier-type allylation mediated by tin, aluminum, and zinc. The reaction is catalyzed by copper and produces tertiary homoallylamines in up to 85% yield.67 The imines generated in situ from 2-pyridinecarboxaldehyde/2-quinolinecarboxaldehyde and aryl amines undergo indium-mediated Barbier allylation in aqueous media to provide homoallylic amines.68 Crotyl and cinnamyl bromides... 

The use of allylindium reagent, generated in situ, makes it possible to introduce the allyl group into C-aromatic aldonitrones, in dimethylformamide DMF-H2O at room temperature (675). Under similar conditions the indium-catalyzed reaction of propargyl bromide with nitrones leads to the corresponding homoalkynyl hydroxylamines (Scheme 2.191) (676). 

Furthermore, the use of a Lewis acid promoter leads to increased stereoselectivities (Table 19, entry C)252,254. Compared to the aprotic reaction, where allyl silane was used instead of allyl bromide and indium chloride, an almost complete reversal of the diastereos-electivity was found. It was demonstrated recently that the Lewis acid catalysed allylation reaction can be carried out efficiently without any organic solvent in saturated ammonium chloride solution255. Finally, Lewis acid catalysed Mannich reactions can be carried out conveniently in mixtures of organic solvents and water. However, the exact role of the Lewis acid catalyst has not been clarified (Table 19, entry D)253. The same reaction can be carried out in pure water with catalysis by indium trichloride256. 

Alkylation products 173 of iminochromenes 159 were synthesized using allyl bromides 174, Nal, and metallic indium. The indium-meditated reaction is accompanied by a complete allyl rearrangement (08SL2791) (Scheme 64). 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

Otherwise, unsaturation may be introduced by use of carbonyl-containing carbohydrate derivatives and carbon nucleophiles that contain alkene (or, if desired, alkyne) functionality, a notable illustration being the tin-or indium-mediated C-l allylation of unprotected sugars. As an illustration, D-arabinose, treated with allyl bromide in aqueous ethanol in the presence of tin gives, after acetylation, 278 in 85% yield.258 In this procedure aldoses react better than do ketoses, and pentoses better than hexoses. More usual is the use of Grignard reactions to give, for example, the octynes 279. 

Highly enantioselective Rh-catalyzed intramolecular Alder-ene reactions for the synthesis of chiral 3-alkylidene-4-vinyltetrahydrofurans were reported by Zhang, as illustrated below <02AG(E)3457>. Metallic indium was also shown to mediate the intramolecular cyclization of tethered allyl bromides onto terminal alkynes to afford 3-methylene-4-vinyltetrahydrofurans in 50-62% yield <02SL2068>. 

Indium-mediated Barbier-type coupling between carbonyl compounds and allyl halides has been revealed to proceed effectively in diverse reaction media. Even under solvent-free conditions, allylation works well, although no reaction is observed with benzyl bromide and a-halo carbonyl compounds.59 Various aldehydes react with allyl bromide mediated by indium in liquid carbon dioxide to give homoallylic alcohols (Scheme 1). In contrast to the corresponding neat allylation, the liquid C02-mediated reaction can allylate solid aldehydes successfully.60 Indium-mediated allylations of carbonyl compounds with allyl bromide proceed in room temperature ionic liquids. In [bmim][BF4] and [bmim][PF6] (bmin l-butyl-3-methylimidazolium), the desired homoallylic alcohols are formed with good levels of conversion.61 Homoallyllic alcohols are also prepared by the reaction of resin-bound aldehydes (Equation (l)).62... 

In indium-mediated reactions, a catalytic use of expensive indium is desirable from an economical standpoint, and it has been achieved in combination with more electron-positive metals. Thus, allylation of aldehydes and ketones, as well as prenylation of 2-chlorobenzoquinone, has been performed by using metallic aluminum or zinc in combination with a catalytic amount of indium(m) chloride.63 Also, allylation of aldehydes and ketones with allyl bromide is carried out with a catalytic amount of indium powder (from 0.01 to 0.1 equiv.) in THF in the presence of manganese and chlorotrimethylsilane as the reducing and oxophilic agents, respectively (Scheme 2). 64,65... 

Anomalous yy/z-diastereoselectivity of indium-mediated coupling of aldehydes with bromides (Z)- and (E)A2 has been reported (Scheme 45). The reaction affords high syn-selectivity (43/44) regardless of the allylic bromide geometry. Preliminary studies on the enantioselective indium-mediated allylation have been attempted and it has been found that the desired products can be obtained in moderate yield with high. //-selectivity and enantioselectivity (Equation (23)).99... 

The coupling reaction of a-keto esters with allyl, propargyl, and allenyl halides using indium metal in aqueous solvents affords a-hydroxy-y,<5-unsaturated esters (Equation (28)).197,198 1,3-Dicarbonyl compounds undergo efficient carbonyl allylation reactions in an aqueous medium through a Barbier-type reaction (Equation (29)). The reaction is general and a variety of 1,3-dicarbonyls has been alkylated using allyl bromide or allyl chloride in conjunction with indium.199... 

Sequential nucleophilic and electrophilic alkylations of 1,3-dicarbonyl compounds with a trimethylenemethane zwitterion equivalent lead to [3 + 2]-annulation. The nucleophilic carbonyl alkylation step has been carried out via an indium-mediated allylation in water (Equation (30)).200 Indium-mediated allylation of a-chlorocarbonyl compounds with allyl bromides in aqueous media gives the corresponding homoallylic chlorohydrins, which can be transformed to allyloxiranes (Equation (31)).201 Allylation of the G3 position of the cephem nucleus has been accomplished by indium-mediated allylation reaction in aqueous media (Equation (32)).202... 

Indium-mediated allylation of cyclic and acyclic acid anhydrides gives w-diallyl esters.203,204 Examples are shown in Scheme 48 the allylation of succinic anhydride or phthalic anhydride with allyl bromide in DMF in the presence of indium metal results in the formation of diallylbutenolides or diallylphthalides. In contrast, monoallylated hydroxy esters are formed exclusively with y-substituted allylic halides. 

Several indium-mediated intramolecular carbonyl allylation reactions have been investigated, and it has been found that these reactions provide an easy access to a variety of cyclic compounds. The intramolecular cyclization of 49a-c mediated by indium in aqueous media proceeds smoothly to afford carbocyclic systems containing y-hydroxy-Q -methylene esters 50a-c, which either spontaneously or readily cyclize to give fused o -methylene-y-butyrolactones 51a-c (Scheme 52). The same cyclization of 49d is too slow to compete with the side-reaction, in which the bromide is substituted by a hydroxy group. The ring junction stereochemistry of fused lactones 51 has been found to be cis in all cases. Of the two possible transition states, the one leading to the m-fused compounds is preferred, because the chair-chair conformation is favored over the chair-boat conformation.209... 

Formyluracils and 4-formylpyrazoles undergo smooth olefinations in THF with indium metal (0.8equiv.), BF3 OEt2 (1 equiv.), and allyl bromide (1 equiv.) providing the respective diene-substituted heterocycles in a single step (Equation (51)).239... 

The allylation of imines with allylindium reagents in organic solvents gives the corresponding homoallylic amines.251-253 Under solvent-free conditions, the indium-mediated reaction of iV-benzylideneaniline furnishes a mixture of mono-allylated 79 and bis-allylated products 80 (Equation (56)). The bis-allylated product 80 presumably arises via a formation of an iminium salt, which is subsequently attacked by the allylindium nucleophiles. Formation of 80 is entirely suppressed by addition of allyl bromide to indium metal prior to any addition of the imine (Grignard-type reaction).254... 

Trifluoromethylaldimine reacts with various allylic bromides, under Barbier conditions in the presence of indium in DMF, to provide the corresponding homoallylamines (Equation (57)).255 a-Methylene-y-butyro-lactams are prepared by the indium-mediated reaction of 2-(bromomethyl)acrylic acid with aldimines (Equation (58)).256... 

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