Indium-mediated addition reaction

The indium-mediated reaction of 2-(bromomethyl)acrylic acid with carbonyl compounds gives the corresponding 7-hydroxy-a-methylene carboxylic acids, and a-methylene-7-lactones are obtained after acidic workup (Scheme 28).80,144-146 The indium-mediated addition of 4-bromocrotonic acid to a variety of aldehydes and ketones proceeds exclusively at the ct-carbon of the carboxylic acid. The effect of solvent, including an ionic liquid, is minimal allowing a wide choice of conditions (Scheme 29).61... 

Indium trichloride promotes catalytically the addition of alkynylstannanes to aldehydes (Table 25).42 Metallic indium also mediates the same Barbier-type coupling between alkynyl halides and aldehydes or ketones to give secondary or tertiary propargyl alcohols (Table 26). Secondary alcohols can be oxidized in situ according an Oppenauer process.395 Thus, alkynyl ketones have been prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They are also obtained via an indium-mediated alkynylation of the relevant acyl chlorides (Table 27).396... 

More recently, the related indium-mediated radical reactions have been widely studied (Scheme 7.13).19 Indium iodide-mediated radical cyclisation was first reported by Cook et al.20 The indium-mediated 1,4-addition of alkyl radicals to (F)-but-2-enenitrile was investigated by using 1-ethylpiperidinum hypophosphite (EPHP) as a hydrogen donor in aqueous media (Scheme 7.13).21 Atom transfer radical cyclisation and reductive radical cyclisation were studied using indium and iodine.22 Indium mediated alkyl radical addition to dehydroamino acid derivatives was also reported.23 The indium-mediated radical ring expansion of a-halomethyl cyclic (3-keto esters, shown in Scheme 7.13, was achieved in aqueous alcohols.24... 

The indium-mediated Barbier reaction has certainly become one of the most popular reactions for creating a carbon-carbon bond under aqueous conditions and has led to spectacular developments in recent years. Compared to other metals, indium is resistant to oxidation, hydrolysis, and has a very low first ionization potential (5.79 eV, in contrast to the second one which is quite normal) which confers on it a remarkable reactivity in Barbier-type reactions. In 1991, Li and co-workers reported the first allylation of aldehydes and ketones mediated by indium in water without any additives or special activation [133]. In particular, the use of indium allowed reactions with acid-sensitive compounds [134] or the preparation of complex carbohydrates such as deaminated... 

The application of indium- and tin-mediated Barbier-Grignard reactions in aqueous solution to the chain extension of unprotected sugars has been reviewed. Some C-5 variants of iV-acetylneuraminic acid have been prepared by the indium-mediated addition of ethyl oc-(bromomethyl)acrylate to variously N-substituted mannosamines," and similar chemistry using (bromomethyl)vinyl phosphonate has led to the phosphonate analogue 12. The reaction of O-protected aldono-1,4- and -1,5-lactones with (2-bromomethyl)-acrylate or -acrylonitrile or 2-bromobutyrolactone mediated by samarium diodide led to chain-extended ulosonic acid derivatives." ... 

In a further example of indium-mediated additions to aldoses, a-(bromo-methyl)acrylic acid added to A-acetylmannosamine in the presence of indium to give branched derivative 27 and its C-4 epimer. Ozonolysis of 27 afforded N-acetylneuraminic acid. In a study of the oxidation of L-sorbose (5% Pt/AlaOa, O2) to 2-keto-L-gulonic acid it was found that the reaction rate and selectivity was improved in the presence of certain tertiary amines. The synthesis of a carbocyclic analogue of iV-acetyl-neuraminic acid is discussed in Chapter 18. 

Among all the nucleophilic addition reactions of carbonyl compounds, allylation reaction has been the most successful, partly due to the relatively high reactivity of allyl halides. Various metals have been found to be effective in mediating such a reaction (Scheme 8.4). Among them, indium has emerged as the most popular metal for such a reaction. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

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... 

The reaction of imines with 2-pyridyl thioesters in the presence of aluminium tribromide or ethylaluminium dichloride afforded /ra r-3,4-disubstituted azetidin-2-ones < 1996T2583>. Similar stereoselective addition of silylketene thioacetals to imines is known in the presence of Lewis acids <1996T2573>. An indium-mediated reaction of ethyl bromoacetate with imines yielded 3-unsubstituted azetidin-2-ones in reasonable yields (Equation 195) <2000J(P1)2179>. 

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 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... 

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... 

Indium-promoted reaction of l,4-dibromo-2-butyne with carbonyl compounds gives 1,3-butadiene derivatives via the allenic indium intermediates (Scheme 56).220 Similar indium-mediated l,3-butadien-2-ylation reactions of optically pure azetidine-2,3-diones have been investigated in aqueous media, offering a convenient asymmetric entry to the 3-substituted 3-hydroxy-/ -lactam moiety (Equation (40)). The diastereoselectivity of the addition reaction is controlled by the bulky chiral auxiliary at Q4 221 222... 

The 1,2-addition of allyl iodide to cyclic and acyclic a,/ -unsaturated carbonyl compounds has been achieved by using indium and indium trichloride. The reactivities of a,/3-unsaturated carbonyl compounds depend upon their structure. The reaction of ketones smoothly undergoes in THF or DMF. In the case of cyclic ketones, however, the solvent plays a crucial role, where much improved yields have been obtained in DMF than in THF (Equation (49)).236 Indium-mediated 1,2-allylation of /3-bromoacrolein produces homoallylic alcohol derivatives (Equation (50)), which can be transformed to cyclopentanones by a Pd-catalyzed cyclization.237,238... 

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... 

Indium-mediated reaction of enamines with allyl bromides gives homoallylamines. The addition of one equivalent of acetic acid accelerates the reaction. An analogous reaction of methyl bromoacetate in place of allylic bromides is also possible. The iminium salts formed by protonation of the enamines are considered to be the intermediates (Scheme 70).271 272... 

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... 

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. 

Intermolecular alkyl radical addition to imine derivatives was studied in aqueous media using indium as a single electron transfer radical initiator. The one-pot reaction based on radical addition to glyoxylic hydrazone provided a convenient method for preparing the a-amino acids. Indium-mediated radical addition to an electron-deficient C=C bond also proceeded effectively to provide a new carbon-carbon bond-forming method in aqueous media (Scheme 7.11).15... 

Scheme 7.10 Indium-mediated tandem radical addition-cyclisation-trapping reactions in aqueous media.

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]. 

One of the best methods developed by Whitesides et al. was an indium mediated direct nucleophilic addition of ethyl 2-(bromomethyl)acrylate to unprotected aldoses in aqueous media [111] (Scheme 36). An other advantage of this reaction is that it can be compatible with a variety of functional groups [111,112], The resulting allyl-compounds were produced in good yield. Ozonolysis, then cyclization of the resulting ketones afforded the corresponding ulosonic acids. 

Cho reported the addition of alkyl radicals from alkyl iodide to a,P-unsaturated ketones, esters, and nitriles mediated by indium in aqueous media. Recently, enantiomeiically pure natural and unnatural a-amino acids have been synthesized from a chiral methyleneoxazolidinone by such a highly diastereoselective 1,4-conjugate addition of alkyl iodides in aqueous media (Eq. 10.31). The zinc-copper conjugate addition reaction exhibits high chemoselectivity with the possibility of using functionalized iodides to afford a single diastereomer in short reaction times with good yields. 

---