Indium-mediated allylations

Indium-mediated allylations of carbonyl compounds have proved to be an important application of the metal. In a typical procedure, a carbonyl compound, an allyl halide, and indium powder are all stirred together in a solvent such as THF or DMF or, remarkably enough, water  

Under these conditions, trivalent allylindium species analogous to Grignard reagents are generated in situ  

The reaction between the allylindium intermediates and the carbonyl substrate, however, does not occur directly, but rather via a cyclic six-membered transition state. Evidence for 

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The indium-mediated allylation carried out with allylstannanes in combination with indium chloride in aqueous medium was reported by Marshall et al.113 Allylindium was proposed as the reaction intermediate. Various aldehydes can be alkylated very efficiently with 3-bromo-2-chloro-l-propene mediated by indium in water at room temperature. Subsequent treatment of the compound with ozone in methanol followed by workup with sodium sulfite provided the desired hydroxyl ester in high yield.114... 

Indium-mediated allylation of an unreactive halide with an aldehyde132 was used to synthesize an advanced intermediate in the synthesis of antillatoxin,133 a marine cyanobacteria (Lyngbya majus-cula) that is one of the most ichthyotoxic compounds isolated from a marine plant to date. In the presence of a lanthanide triflate, the indium-mediated allylation of Z-2-bromocrotyl chloride and aldehyde in saturated NH4C1 under sonication yielded the desired advanced intermediate as a 1 1 mixture of diastereomers in 70% yield. Loh et al.134 then changed the halide compound to methyl (Z)-2-(bromomethyl)-2-butenoate and coupled it with aldehyde under the same conditions to yield the desired homoallylic alcohol in 80% yield with a high 93 7 syn anti selectivity (Eq. 8.55). 

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. 

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... 

The indium-mediated allylation reaction in aqueous media has been applied to the studies on the total synthesis of dysiherbaine (Scheme 8.18).159... 

A chemoenzymatic methodology has been developed using indium-mediated allylation (and propargylation) of heterocyclic aldehydes under aqueous conditions followed by Pseudomonas cepacia lipase-catalyzed enantioselective acylation of racemic homoallylic and homo-propargylic alcohols in organic media.192... 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

Indium-mediated allylation reactions of a-keto imides derived from Oppolzer s sultam proceeded in aqueous THF in good yields and excellent diastereoselectivity (Eq. 11.43).74 The indium-mediated allylation of the Oppolzer camphorsultam derivatives of glyoxylic oxime ether... 

Stereoselective allylation of aldehydes is another preferred strategy for the synthesis of appropriate intermediates for the total synthesis and introduction of hydroxy functionalities. Park and co-workers <2003S2473> proposed a synthesis of castanospermine 228 through a key indium-mediated allylation in the presence of (+)-cinchonine of an a-amino aldehyde 247 derived from D-glucono-O-lactone (Scheme 53). 

Indium mediated allylation of 4-acetoxy-2-azetidinones gave the products 57 in high yield <99SL447> and similar reactions with azetidin-2,3-diones gave 3-substituted 3-hydroxy-P-lactams 58 <98H97>. 

Annnlation methodology based on indium-mediated allylation reactions in water (Li and Lu, 1996)... 

Dialkynyl ligands, in platinum(II) complexes, 8, 545 iV,iV-Diallylamine, via allyindium reagents, 9, 703-704 Diallyl clusters, in trirutheniums and triosmiums, 6, 773 gem-Diallyl esters, via indium-mediated allylation, 9, 677 Diallyl ethers, isomerization, 10, 90 Diamagnetic ylides, with gold(II), 2, 278 Diamides... 

Di(carbene)gold(I) salts, oxidation, 2, 293—294 Dicarbido clusters, with decarutheniums, 6, 1036 Dicarbollide amides, with tantalum, 5, 184 Dicarbollide thorium complexes, synthesis and characterization, 4, 224—225 Dicarbollyl ligands, in nickel complexes, 8, 185 Dicarbonyl complexes arylation with lead triacetates diastereoselectivity, 9, 389 enantioselectivity, 9, 391 mechanisms, 9, 387 reaction examples, 9, 382 indium-mediated allylation, 9, 675 with iridium, 7, 287 reductive cyclization, 10, 529 in Ru and Os half-sandwiches, 6, 508 with Zr—Hf(II), 4, 700... 

Grignard additions, 9, 59, 9, 64 indium-mediated allylation, 9, 687 in nickel complexes, 8, 150 ruthenium carbonyl reactions, 7, 142 ruthenium half-sandwiches, 6, 478 and selenium electrophiles, 9, W11 4( > 2 in vanadocene reactions, 5, 39 Nitrites, with trinuclear Os clusters, 6, 733 Nitroalkenes, Grignard additions, 9, 59-60 Nitroarenes, and Grignard reactivity, 9, 70 Nitrobenzenes, reductive aminocarbonylation, 11, 543... 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

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... 

Indium-mediated allylation of m/<9-2-acetoxybicyclo[2.2.1]heptan-7-one shows poor diastereoselectivity.129 On the contrary, indium-mediated allylation of the bicyclic aldehyde has been performed with different solvent systems, and the homoallylic alcohols 10 and 11 are formed in excellent yields with high diastereoselectivity. The highest diastereoselectivity has been observed in DMSO in 94% yield (Scheme 16).130 Indium-mediated propargylation of the same aldehyde gives two diastereomers in 94% yield in a ratio of 60 40 (Equation (9)).130... 

Table 1 Indium-mediated allylation of a-oxygenated aldehydes. Reproduced with permission from ACS Publications...

Indium-mediated allylation of the sugar derivatives in aqueous media proceeds with high anti diastereofacial selectivity in the presence of ytterbium triflate as a Lewis acid (Equation (18)).173... 

Indium-mediated allylation of c -keto-/3-lactams such as 6-oxopenicillanate and 7-oxocephalospranate proceeds diastereoselectively to afford a-allyl-/3-lactams in aqueous media (Scheme 42). In the cinnamylation of the mono-cyclic compound, the diastereofacial selectivity is directly linked to the (R)- or (A)-configuration of the exocyclic A-substituent (Scheme 43).175,176-180... 

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... 

Pan et al. reported similar reactions of / -quinones to 4-allyl-4-hydroxycyclohexa-2,5-dienone derivatives (Equation (26)).194 Unsymmetrical quinones show high selectivity in the addition of allylindium reagents to the carbonyl group. Indium-mediated allylation of 1,2-diones occurs via a y-coupling fashion to yield ct-hydroxy keto compounds. In some cases of cinnamylation, the corresponding a-coupling products are obtained (Equation (27)).195,196... 

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. 

One-pot sequential double nucleophilic attacks using two different nucleophiles to a molecule having identical functionalities have been established via indium-mediated allylation involving an HOAc quenching after the first allylation (Scheme 51).208... 

Treatment of acyl phosphates with allylindium reagents in the presence of acetic acid affords the corresponding a-hydroxy phosphonates in good yields under mild conditions (Equation (52)).240 (3-Keto phosphonates give the corresponding / -hydroxy phosphonates in good yields by indium-mediated allylations (Equation (53)).241... 

Indium-mediated allylation of trialkyl(difluoroacetyl)silane 70 in aqueous media gives homoallylic alcohol 71 exclusively (Scheme 60). Both water and THF are essential for the allylation reaction. It is worth noting that homoallylic alcohol 71 is formed exclusively under these reaction conditions. On the contrary, enol silyl ether 72 is a major product of the fluorinated acylsilanes reaction with other organometallic compounds than indium via a Brook rearrangement and defluorination. Indium-mediated allylsilylation of carbonyl compounds provides a facile route to 2-(hydroxyethyl)allylsilanes. The allene homologs are similarly prepared (Scheme 61).244,244a... 

Diastereoselective Barbier-type allylation of chiral imines bearing a hydroxyl group on the chiral auxiliary has been achieved in DMF (Equation (59)).257-259 The chelation between the nitrogen and the hydroxyl group of the imine with indium is crucial for the high stereoselectivity. The palladium-catalyzed indium-mediated allylation of imines also proceeds well with Ini prepared in situ from In and I2.259... 

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