Allylindium

Whitesides et al. examined the effect of substituents on the allyllic moiety of the indium-mediated reactions in water and found that the use of indium at room temperature gave results comparable to those of tin-mediated reactions carried out at reflux.110 Replacement of the aqueous phase with 0.1 N HC1 further increased the rate of the reaction. The transformation can also be carried out with preformed allylindium chloride. 

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... 

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 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). 

Homoallylic alcohols are provided by Pd-catalyzed reaction of iodobenzene, allene and aldehydes (Scheme 16.15) [19, 20]. A nucleophilic allylindium intermediate is generated through transmetallation of a Jt-allylpalladium species with indium. Such a Jt-allylpalladium complex can alternatively be provided through carbopalladation of ArPdl to a proximate acetylene followed by insertion of allene. 

Allylindiums were found to be highly active reagents to react with terminal alkynes to yield allylated products.451 In a similar fashion efficient allylation can be mediated by indium metal under mild conditions 452... 

Allylaziridines have been prepared in good yield by the action of allylindium reagents on azirines (e.g. 25).63 The C(3) substituent can control stereochemistry hydroxy- (or acetoxy-) -methyl gives d.v-allylalion (via chelation with the indium (g) reagent), whereas R = Me/Ph/C02Et gives a trans result, presumably due to steric repulsion. 

A new study has revealed that allylmagnesium, allylindium, and allylbismuth generally exhibit a preference for axial addition to cyclohexenones (in the 1,2-addition). Allylmagnesium was found to be the most stereoselective reagent. Reactions with carvone (an a-methylated enone) were most selective, except that allylbismuth was inert to this substrate.225... 

A three-component reaction based on the umpolung of re-allylpalladium (II) complexes indium metal was reported by Grigg and co-workers (Scheme 8.31) [74]. In this reaction, the electrophilic nature of the n-allyl palladium species generated from aryl halides and allenes is reversed by transmetallation with indium metal. The resultant nucleophilic allylindium reagent subsequently adds to the third component - aldehyde [75] or imine [76] - to give the corresponding homo-allylic alcohol 64 or amine 65 respectively. 

Oxozirconocenes, preparation, 4, 916—917 7-Oxygenated allylindium reagents, in carbonyl allylations,... 

Hirashita, T. Kamei, T. Horie, T. Yamamura, H. Kawai, M. Araki, S. Preparation of y-het-erosubstituted allylindium and diindium reagents and their reactions with carbonyl compounds./. Org. Chem. 1999, 64,172-177. Yamaguchi, M. Mukaiyama, T. The stereoselective synthesis of d- and L-ribose. Chem. Lett. 1981, 1005-1008. 

Using a BINOL auxiliary with allylindium and indium metal, hydrazones have been allylated enantioselectively,92 to give homoallylic amines in up to 97% ee. 

Reactions of allylindium derived from allylic dihalo compounds 681... 

Reactions of Allylindium Prepared by Redox Transmetallation with Pd or Ni 698... 

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... 

A new preparative method for allylic indium(m) reagents via a reductive transmetallation of 7r-allylpalladium(n) or 7T-allylnickel(n) complexes with indium(i) salts is reported. This method enables the use of a wide variety of allylic compounds, such as allylic chlorides, acetates, and even allylic alcohols, in combination with Pd or Ni catalysts.43-50 7r-Allylpalladium(ii) resulting from the addition of arylpalladium(n) to allene is also transformed by metallic indium to the corresponding allylindium.51-54 Similarly, propargylindium(m) can be prepared from the corresponding propargyl alcohol derivatives.55-58... 

Allylindium prepared in situ from allylmagnesium bromide with indium trichloride reacts with aldehydes in THF-H20 to afford homoallylic alcohols. The yield is higher when water is present rather than under anhydrous conditions (Equation (2)).67... 

Allylindium and propargylindium reagents have successfully been applied to the total syntheses of several natural products.68-101... 

Allylindium reagents bearing substituents at the 7-position react with carbonyl compounds in organic and aqueous media regioselectively at the 7-position, via a six-membered transition state, to afford the corresponding branched homoallylic alcohols, if no sterically bulky carbonyl or allyl substituent is involved.102 For example, the indium-mediated reaction of aldehydes with 3-bromo-l-cyano-l-propene proceeds readily in water to give cr-cyano-f3-ethylenic secondary alcohols (Scheme 4).103... 

Pentadienylindium, a vinylog of allylindium, reacts with carbonyl compounds regioselectively at the 7-position to give 1,4-pentadiene derivatives (Scheme 7).107-109 n the presence of InCl3, pentadienylstannane similarly reacts with a-alkoxyaldehydes to produce the corresponding 7-adducts (Scheme 8).110... 

The reaction of allylindium sesquibromide with 4 equiv. of bulky lithium alkoxide results in modified reagents 7, which show unusual degrees of chemo- and diastereoselectivity in the reactions with carbonyl compounds for example, allylation of 2-methylcyclohexanone gives a high ratio of axial alcohol 8/equatorial alcohol 9 (Scheme 15).128... 

The stereochemical outcome can be rationalized by considering the approach of the aldehyde to the preferred conformation of the allylindium. The approach of the aldehyde is postulated to be in antiperiplanar to the OPG group as for the Felkin-Anh model. The allylindium prefers to adopt the conformation 12 rather than 13, where the 1,3-allylic strain with R is minimized and the steric interaction with the aldehyde is also reduced (Scheme 18). The facial selection with respect to the aldehyde is determined by the aldehyde residue (R ) to occupy in the least sterically demanding position, away from the substituted allylic carbon. The carbonyl allylation then proceeds via a six-membered chairlike transition state, in which the aldehyde substitutent attains an equatorial position, to afford the 1,4-syn product. 

The O-silylated allylindium shows moderate //////-selectivity, via the Felkin-Anh transition state, while the hydroxy-bearing allylindium exhibits. //-selectivity by dual coordination of indium intramolecularly to the hydroxy group and intermolecularly to the aldehyde (Scheme 20).133 With the CH2OH now locked below the developing chair, the R substituent could become the key factor. The easy accessibility of the aldehyde in 15 leads to the highly preferred formation of 1,4-syn products relative to 16 (Scheme 21). 

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