Allylindium, addition

The diastereoselective allylindium addition to norbornyl cr-diketones leads to acyloins. The diastereoselection in the case of monoallylation products greatly depends on the nature of 5-endo substituents. Non-chelating groups direct the addition from the sterically less congested exo-face, diagonal to the substituent, whereas chelating substituents, such as an alkoxy or acetoxy unit, induce a complete reversal in the selectivity (Equation (16)).169... 

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. 

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... 

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... 

The effect of proximal groups on the diastereoselectivity in the addition of allylindium to a carbonyl group has been extensively surveyed.153 When a- and /3-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol is realized, syn- 1,2-Diol and anti- 1,3-diol products are formed, respectively, at accelerated rates (Tables 1 and 2). Protection of the free hydroxy group results in the alternative formation of 1,2-anti products. High stereoselectivities have been observed for indium-promoted allylations of a- and /3-hydroxy aldehydes in aqueous media, implying that a chelate control still operates even in water.72,73,154-158... 

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... 

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... 

Allyl and benzyl bromides react with a,/ -unsaturated nitriles in the presence of indium(i) iodide under sonication to produce the corresponding allylated and benzylated imines, involving exclusive addition of the allyl/benzyl group to the nitrile moiety (Equation (63)).273 The reaction of allylindium reagents with methyl cyanoacetates affords the corresponding allylation-enamination products (Equation (64)).27 l-Acyl-l,2-dihydropyridines are prepared by indium-mediated allylation of 1-acylpyridinium salts (Equation (65)).275 Quinoline and isoquinoline activated by... 

Indium-mediated allylation of a nitro group is achieved in aqueous media to give A,A-diallylamine and 7V,0-diallylhydroxylamine (Equation (81)) 316 In situ generated sulfonium salts derived from a,/3-enones undergo a nucleophilic substitution with allylindium reagents to give the corresponding Michael addition products (Scheme 83).317... 

The alkenylindium compounds, obtained by the addition of benzyl- and allylindium to alkynes, couple with organic halides in the presence of a palladium catalyst to give the three-component coupling products (Scheme 99).286 1,3-Dibromopropene or 3-bromo-l-iodopropene reacts with indium to give diindiopropene 87a,b.147,148 This dimetallic reagent reacts with two different electrophiles successively carbonyl compounds and imines are allowed to react with 87 as the first electrophile to give vinylic indium intermediates 88, which react with... 

Triorganogallium and -indium reagents react with a,/3-unsaturated nitrile, ketone, and ester to give 1,4-addition products regioselectively (Table 31). In contrast, the reaction of allylgallium and allylindium sesquihalides with a,/3-unsaturated carbonyl compounds proceed in a 1,2-addition mode, whereas 1,4-addition takes place with a,/3-unsaturated nitriles.294... 

Addition to cyclopropenes. Addition of allylindiums to the more substituted carbon atom of the double bond is observed. Carboxyl and hydroxymethyl groups have directing effect. 

The diastereoselective production of homoallylic indium alkoxides can be accomplished by a kinetic resolution process [194]. The indium-mediated reaction of benzaldehyde with 2-butenyl bromide has always been observed to be unselec-tive. The use of alkoxide or halide modifiers in the reactions of allylindium reagents has previously been shown to provide synthetically useful reagents [195], Upon addition of 2-butenylindium sesquibromide to benzaldehyde it was determined that newly formed syn and anti homoallylic alcohols undergo decomposition at a similar rate, but as the concentration of the anti homoallylic alcohol reaches zero, the rate of decomposition of the syn alcohol slows dramatically. Thus, the syn homoallylic alcohol can be obtained in high diastereoselectivity, albeit low yield. 

From an extensive examination of the addition of allylindium reagents to a-oxygenated aldehydes 291 it has been established that the stereochemical outcome is dependent on both the a-alkoxy substituent and the solvent employed (Table 10-33) [197]. The silyl and benzyl ethers favor the formation of the anti homoallylic alcohol, whereas the MOM and the hydroxyl aldehydes favor the syn alcohol. The rate of the reaction is dependent upon the solvent (faster in a mixed THF/water solvent) and the pH (faster at lower pH). 

Table 10-33. Addition of allylindium bromide to -oxygenated aldehydes.

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]. 

Paquette and co-workers have extensively surveyed the effect of proximal groups on diastereoselectivity in the addition of allylindium to a carbonyl group. When a-and yS-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol... 

The 1,4-conjugate addition of triorganoindium to enones is promoted by a catalytic amount of Ni(COD)2 (Scheme 8.71) [100], Allylindium reagents can be used in Pd-catalyzed cross-coupling reaction with aryl halides (Scheme 8.72). The Pd-catalyzed allylic substitution of allyl carbonate produces 1,5-dienes (Scheme 8.73) [101]. The indium-mediated palladium-catalyzed Ullmann-type reductive coupling of aryl halides proceeds in aqueous media under air (Scheme 8.74) [102]. 

Stannanes and silanes may act as carbanion derivatives that can be activated with suitable Lewis adds. Thus, as shown by Cossy et al. [440], allylstannanes may be transmetalated with InCU to generate allylindium derivatives in situ. The latter can react with aldehydes to give mixtures of syn and anti adducts (with aromatic aldehydes and 2-buten-l-al). With aliphatic aldehydes, only the anti adducts are observed. The authors concluded that product mixtures were partly caused by the kinetic formation of a mixture of indium (Z)- and ( )-allyl esters prior to the condensation. They then allowed the indium species to equilibrate prior to the aldehyde addition and obtained mainly anti adducts (627, 628) (Scheme 130). 

The enantioselective asymmetric allylation of imines has been a synthetic challenge, the initial solutions of which required stoichiometric amounts of chiral allylbor on [87], allylsilane [88], allylzinc [89], or allylindium reagents [90]. Itsuno showed that a chiral B allyloxazaborolidine derived from norephedrine could add to the N trimethylsilyl imine prepared from benzaldehyde in high yield and enantiomeric excess (Scheme 1.22) [91]. Brown later reported that B allyldiisopinocamphenylbor ane is also very effective for the allylation of the same electrophiles, but the addition of a molar amount of water is necessary to obtain high yields [92]. The diastereo and... 

Cook reported that a 3,3 bis(trifluoromethyl) BINOL catalyzed asymmetric addition of allylindium to hydrazones proceeds in modest to good enantioselec tivities (10 92% ee) [90]. The stoichiometric version of this reaction yields much higher enantioselectivities (84 97% ee). Jacobsen later found that a chiral urea catalyst is effective in catalyzing a similar transformation [96]. The bifunctional catalyst 55 bearing a hydrogen bond donor and a Lewis base that are properly... 

Similarly, the use of CTAB and EPHP in presence of 4,4 -azobis(4-cyanovaleric acid) (ABCVA) promoted the indium-mediated radical addition to /(-substituted cconjugated alkenes in water. This method produced 1,4-addition products to afi-enones while the classical allylindium reagents lack generally of regioselectivity [113]. 

W. Lee, K.-H. Kim, M. D. Surman, and M. J. Miller, Stereo- and regioselectivity of Pd/In mediated allylic additions to aldehydes and ketones. In situ generation of allylindium(III) intermediates from /V-acylnitroso Diels-Alder cycloadducts, and 1 -amino-4-acetoxycyclopentanes, J. Org Chem., 68 (2003) 139-149. 

Cooper et al. reported that the cascade reaction of the palladium-catalyzed cyclization and the Barbier-type allylation of the 1,3-diene-aryl iodide 514, the aldehydes 515, and indium gave the heterocycles 516 in good yields (Scheme 154).220b The reaction proceeds through oxidative addition of a C—I bond of 514 to Pd(0) and subsequent insertion of a double bond of 517 to give the jr-allylpalladium intermediate 518. Transmetalation of the jr-allylpalladium 518 with indium leads to the allylindium complex 519, and the following reaction with the aldehydes 515 gives 516. 

Addition and substitution. Addition of allylindium reagents to allenyl carbinols affords linear products. A net l,3-butadien-2-ylation at the (3-carbon of p-acetoxy-p-lactams results when they are treated with indium and l,4-dibromo-2-butyne. ... 

Dibromopropene acts as a gem-allyl dianion synthon. However, the reaction is not as clean as one might desire, due to competing reductive debromination of the 1 1 products., l-Dichloro-2-propene undergoes a y-selective addition process, affording syn-chlorohydrins, but the allylindium species derived from 3-bromo-l-trimethylsilylpropene attacks aldehydes with the a-carbon. ... 

Factors influencing the stereoselectivities observed for the 1,2-addition of various allylindium reagents to aldehydes and ketones in aqueous media have been investigated. Described herein are the mechanistic rationales based upon the adoption of either internally chelated (Cram-like) or Felkin-Anh transition states. 

By every indicator we have uncovered, chelation to indium(III) is seen to operate in water where possible, with resultant control of reaction diastereoselectivity. Erosion of selectivity is sometimes encountered, but the causative factors are exu insic to the chelation phenomenon. In this connection, a comparative analysis of additions involving crotylindium and 3-bromoaIlylindium to 2-hydroxypropanal is particularly informative (Scheme 2) (/6). In the case where R is methyl, the proportion of the syn,syn and syn,anti isomers is maximized at 5.6 1, a value closely comparable to that for simple allyladon (syn/anti = 7.5 1). When R = Br, the maximum value is only 2 1. In fact, the latter process qualifies as a fully nonselective process. The prevailing hypothesis is that this behavior is linked to facile geometric isomerization in the allylindium species as noted for the Grignard (77), potassium 18), and lithium derivatives (79). 

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