Allylic indium reagents

The preparation and subsequent reaction of allylic indium reagents with aldehydes or ketones was first reported by Butsugan in 1988 [190]. The reaction of the 2-butenylindium reagents with aldehydes produced homoallylic alcohols in high yield albeit low selectivity. 

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Allenic alcohols couple with allyl indium reagents at 140°C to give allylic alcohol products. Similarly, (o-hydroxy lactones couple with organoindium reagents. 

The control of diastereoselectivity in the allylation reaction of carbonyl compounds with allylic indium reagents has been an important issue since the discovery of the indium-mediated carbonyl allylation. As earlier discussions have been summarized in the precedent reviews,6-24 only relatively recent references are cited below. 

Indium trichloride-mediated addition of (i )-a-(methoxymethoxy)allylic stannane (>95% ee) to cyclohexanecarbox-aldehyde affords the anti-adduct predominantly (anti syn = 98 2) and stereoselectively (>95%ee) (Equation (12)). Production of a transient allylic indium reagent is postulated via a stereosepecific anti-Se2 transmetallation. This a-(methoxymethoxy)allylic stannane reacts without allylic inversion, whereas the reaction of crotylstannane in Equation (5) (Section 9.14.3.3.1) proceeds with net allylic inversion. <5-Oxygenated allylic stannane also undergoes transmetallation with InCl3, and in situ addition to a-ODPS acetaldehyde leads mainly to the //-adduct, which is a potential precursor to D-(+)-altrose (Scheme 31).149,150... 

The high anti selectivity observed in these additions with both branched and unbranched aldehydes makes the oxygenated allylic indium reagents well suited for applications related to annonaceous acetogenins [74]. The following examples are illustrative (Eqs 55-58). 

A possible explanation might lie in the experimentally determined relatively poor reactivity of enals, compared with ynals, toward these allylic indium reagents. The slower rate of addition would enable equilibration of the kinetic (E) allylic indium intermediate to a mixture of E) and (Z) isomers. The latter would afford the syn adduct. 

Achiral allylic indium reagents and chiral aldehydes. Allylindium reagents generated in water react smoothly with aldehydes and ketones (Scheme 10-99) [196], The reaction of achiral aldehydes and a-oxygenated aldehydes 290 with the allyl indium reagents proceeds smoothly to homoallylic alcohols without the need for external promoters. It is interesting to note that the a-hydroxyl aldehyde was se-leetive for the syn (chelation-eontrolled) product even in water. 

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. 

Figure 10-10. Transition structure models for substituted allylic indium reagents.

The generation of allylic indium reagents by transmetallation of allylic stannanes with InCl3 and subsequent reaction of these with aldehydes represents an important advance for diastereoselective synthesis of homoallylic alcohols [203]. In these reactions, the stannane is added to a premixed solution of the aldehyde and InCl3 in acetone. In this way, the reaetion of cyclohexanecarboxaldehyde with the 2-butenylindium reagent affords a 98/2 antilsyn mixture of homoallylic alcohols (Scheme 10-104). 

The L-talo and L-gulo adducts 447 and 449 were obtained with very high stereoselectivity (no other diastereomers reported) from the reaction of aldehyde 444 with the [y-(alkoxy)allyl]indium reagents generated from (5)-230a and (R)-230a, respectively. In these double asymmetric reactions, reagent control is clearly dominant. The stereochemistry of adduct 447 is rationalized by the Felkin transition state 448 while the stereochemistry of adduct 449 is rationalized by the anti-Felkin transition state 450 [275]. 

The use of InCls for Lewis acid activation of aldehyde substrates leads to rapid transmetalation of the allylic stannane, followed by carbonyl addition reactions of an allyl indium reagent. Premixing of InCb and the allylic stannane in the absence of aldehyde often produces precipitation and poor results. On the other hand, allyl indium reagents have been independently prepared by several procedures, including reductive metalations. Several important reviews describe the methods of preparation and the reactivity of allyl indium compounds. This discussion will be limited to key factors regarding the transmetalation of allylic stannanes in the presence of aldehydes. Stereochemical events leading to the production of anti adducts as major products are illustrated in Scheme 5.2.55. 

In the past decade much effort in organoindium chemistry has been devoted to study of carbonyl allylation and aUylindation of carbon-carbon multiple bonds with allylic indium reagents. Apart from the conventional transmetalation of allyl-lifhium or aUyl Grignard reagents with indium(III) halides, a method widely used for preparation of allyhndium(III) compounds is the oxidative addition of metallic indium or indium(I) iodide to aUyhc substrates [3, 6]. Transmetalation of allylstan-nane with indium(III) chloride also gives allylindium(III) [7]. Allylindium(I) was recently prepared by transmetalation of allylmercury with metallic indium in water this compound is regarded as an intermediate in the allylation of carbonyl compounds in aqueous media [8]. A new method of preparation of allylic in-dium(III) reagents - reductive transmetalation of a 7r-allylpalladium(ll) complex with indium(I) salts has been reported this enables the use of a wide variety of allylic compounds and solvents [9]. 

Stereoselective 1,4-asymmeric stereoinduction under aqueous conditions is realized by use of oxygen-substituted allylic indium reagents (Tab. 8.5) [30]. O-Silylated allylindium shows moderate anti selectivity, via the FeUdn-Anh transition state, whereas hydroxy-bearing allylindium exhibits syn selectivity by dual coordination of indium intramolecularly to the hydroxy group and intermolecularly to the aldehyde. 

Tab. 8.5 Reaction with oxygen-substituted allylic indium reagents...

Accordingly, the desired diol mono ethers 34 were synthesized in high yields with complete regiocontrol by the reaction of aldehydes with y-alkoxy allyl indium reagents (35 — 34a) (Scheme 9) (07OL953, 08T809). Acylation... 

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