Allylic alcohol carbonyl compounds

The allylation of carbonyl compounds in aqueous media with SnCl2 can also employ allylic alcohols (Eq. 8.39)84 or carboxylates85 in the presence of a palladium catalyst. The diastereoselectivity of the reactions with substituted crotyl alcohols was solvent dependent. Improved diastereoselectivity was obtained when a mixture of water and THF or DMSO was used, instead of the organic solvent alone. 

The allylation of aldehydes can be carried out using stannous chloride and catalytic cupric chloride or copper in aqueous media." In-situ probing provides indirect (NMR, CV) and direct (MS) evidence for the copper(I)-catalyzed formation of an allyltrihalostannane intermediate in very high concentration in water (Scheme 8.6). Hydrophilic palladium complex also efficiently catalyzes the allylation of carbonyl compounds with allyl chlorides or allyl alcohols with SnCl2 under aqueous-organic... 

Ga. Gallium was used to mediate the allylation of carbonyl compounds in water.170 The reaction can also be carried out by using preformed allylgallium reagents.171 The corresponding homoallyl alcohols were obtained in high yields without the assistance of either acidic media or sonication (Eq. 8.72). 

Ge. Scandium(III) triflate-catalyzed allylation of carbonyl compounds with tetraallylgermane proceeded readily in aqueous nitromethane to afford homoallyl alcohols in excellent to good yields.175 The presence of H20 is indispensable for the allylation of aldehydes to proceed smoothly. Aldehydes were allylated exclusively in the presence of ketone moieties (Eq. 8.74). 

Durandetti et al. have described iron-catalyzed electrochemical allylation of carbonyl compounds with allylic acetates (Equation (27)).333 In the case of aldehydes, slow addition of the corresponding aldehyde is required in order to avoid pinacol formation. With crotyl acetate (R3 = Me), the reaction proved to be highly regioselective, providing almost exclusively branched homoallylic alcohols 150. 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

Allylation of carbonyl compounds. The coupling reaction of allylic bromides with carbonyl compounds such as aromatic and aliphatic aldehydes as well as ketones leads to the corresponding allylic alcohol in good yields (54-85%) and with high regioselectivity (see, for instance, equation 16)25. 

The electrochemical allylation of carbonyl compounds by electroreductivc regeneration of a diallyltin reagent from allyl bromide and a Sn species leads to formation of homoallylic alcohols in yields of 70-90 % even in methanol or methanol/water (Table 7, No. 12) Bisaryl formation is possible also from aryl iodides or bromides in the presence of electro-generated Pd phosphane complexes (Table 7, No. 13) In the presence of styrenes, 1,3-butadienes, or phenyl acetylene the products of ArH addition are formed in this way (Table 7, No. 14) . The electroreductivc cleavage of allylic acetates is also possible by catalysis of an Pd°-complex (Table K No. 15)... 

Hydroperoxide formation is characteristic of alkenes possessing tertiary allylic hydrogen. Allylic rearrangement resulting in the formation of isomeric products is common. Secondary products (alcohols, carbonyl compounds, carboxylic acids) may arise from the decomposition of alkenyl hydroperoxide at higher temperature. 

Indium mediates the coupling of a,a-difluoroallyl carbanion with aldehydes, to give geuz-difluorohomoallyl alcohols.89 hi contrast to many comparable allylations of carbonyl compounds, ketones do not react. 

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

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... 

The indium-promoted allylation of carbonyl compounds in the presence of cinchona alkaloids (2 equiv), as a route to chiral allylic alcohols, was recently reported by Loh [20, 21]. The reaction is applicable to a variety of aldehydes and ketones. The enantioselectivities obtained with allyl bromides as the substrate are at the best moderate (up to 75% ee) [20]. However, the use of prenyl bromides as substrates... 

Allylation of carbonyl compounds with tetraallylgermane [21] is promoted by a catalytic amount of Sc(OTf)3 in CH3NO2 to afford the corresponding homoallylic alcohols in high yields. It was found that addition of small amount of H2O significantly increased the yields of the adducts (Scheme 11.9) [22]. 

Bu3Bi mediates the allylation of carbonyl compounds with allyl bromide to give a mixture of homoallyl alcohols and fheir allyl ethers (Scheme 14.133) [278], Tris(4-methoxyphenyl)bismuthane catalyzes the cyanation of carbonyl compounds with MesSiCN [175], In the presence of fluoride ions (CeFsjsBi undergoes nucleophilic substitution with an activated C-F bond of perfluorinated compounds to transfer three CgFj groups [279]. (CFsjsBi can also act as a trifluoromethyl anion equivalent [280]. 

The SnCl2-mediated allylation of carbonyl compounds is even possible with allylic alcohol or its corresponding methylcarbonate in the presence of palladium catalyst (Scheme 26) [123]. In the reaction of (E)-but-2-enoI with benzaldehyde in the presence of SnCl2, the rate and the anti selectivity were shown to increase with the amount of water in the reaction mixture [124]. 

Asymmetric allyation of carbonyl compounds to prepare optically active secondary homoallyhc alcohols is a useful synthetic method since the products are easily transformed into optically active 3-hydroxy carbonyl compounds and various other chiral compounds (Scheme 1). Numerous successful means of the reaction using a stoichiometric amount of chiral Lewis acids or chiral allylmetal reagents have been developed and applied to organic synthesis however, there are few methods available for a catalytic process. Several reviews of asymmetric allylation have been pubHshed [ 1,2,3,4,5] and the most recent [5] describes the work up to 1995. This chapter is focussed on enantioselective allylation of carbonyl compounds with allylmetals under the influence of a catalytic amount of chiral Lewis acids or chiral Lewis bases. Compounds 1 to 19 [6,7,8,9,10,11,12,... 

Since the observation that allylation of carbonyl compounds could be mediated by tin in aqueous medium [77], there has been an intensive development of the Barbier-type allylation reaction in water. Three metals were particularly investigated zinc, tin, and indium. In the aqueous zinc-promoted allylation, allylzinc species are considered unlikely. The initiation of the reaction could be attributed to the formation of an allylic radical anion on the metal surface this radical surface could then react with the carbonyl compound to give an alkoxide radical, which could add an electron and form the alcohols [82]. Allyl bromide or even chloride reacts with aldehydes and ketones in the presence of commercial zinc powder in a mixture of tetrahydrofuran and saturated ammonium chloride aqueous solution (Eq. 7) [83]. 

Homoallyl alcohols. Indium(III) iodide catalyzes allylation of carbonyl compounds by allylstarmanes. 

Homoallylic alcohols. Allylation of carbonyl compounds is straightforward. Under catalyzed conditions enones undergo conjugate addition. 

Homoallyl alcohols. The tin reagent effects chemoselective allylation of carbonyl compounds in aqueous acidic media. 

The allylation of carbonyl compounds via allylboration, allylstannation, and Sc(CF3S03)3- " or InCl3- mediated process for the generation of a variety of homoallylic alcohols has been performed in various imidazolium ILs. The enantioselective allylation of aldehydes has been performed by In(iii) complexes associated by PYBOX ligands in [C4GiIm]PF6 (Scheme... 

N. Selander, A. Kipke, S. Sebehus, K. J. Szab6, J. Am. Chem. Soc. 2007, 129, 13723-13731. Petasis borono-Mannich reaction and allylation of carbonyl compounds via transient allyl boronates generated by palladium-catalyzed substitution of aUyl alcohols. An efficient one-pot route to stereodefmed a-amino acids and homoaUyl alcohols. 

Finally, Chen s work on the direct allylation of carbonyl compounds using benzyl alcohol in the multicomponent Sakurai reaction catalyzed by selective and green solid acids, such as sihcomolybdic acid (SMA-SiO ) [92] or perchloric acid (HClO -SiOj) [93], both supported on silica gel, should be mentioned. In some cases, the use of preformed acetals as substrates provided better results. These methods allowed the synthesis of a broad number of homoallylic ethers in moderate to high yields in a short reaction time. Significantly, catalyst loading of HClO -SiOj is only 2mol%. 

Moreover, it was found that nanometer-sized bismuth mediates the allylation of carbonyl compounds in water to afford the corresponding homoallylic alcohols in high yields. Nanometer-sized bismuth is much more effective than regular bismuth powder in this reaction. The regioselectivity of the reaction depends on which kind of nanometer-sized bismuth (Bi nanotubes or in situ Bi nanoparticles) is used (Equation 2) [25b]. 

Allylation of carbonyl compounds is another very useful carbon-carbon bond forming asymmetric transformation in organic synthesis. This transformation yields the homoallylic alcohols that have proven to be valuable reagents and intermediates that have found numerous applications in natural product total synthesis. In particular, asymmetric allyl-boration of aldehydes employing tartrate- and pinane-derived reagents has been widely exploited. Although the asymmetric allylation reaction is well documented and widely used in solution phase, the asymmetric variant of the allylation of carbonyl compounds on the solid support has remained largely unexplored. ... 

The Lewis acid-mediated allylation of carbonyl compounds leading to homoallylic alcohols constitutes one of the most important synthetic reactions. Numerous allylic organometallic reagents and Lewis acids have been investigated. The low-temperature boron halide-mediated allylation of cycUc ketones using allylstannane to give homoallylic alcohol has also been reported. ... 

The allylation of carbonyl compounds and the carbonyl-ene reaction offer ready access to the synthetically useful homoallylic alcohols. However, both these reactions produce predominantly y-adducts. Loh and co-workers have reported the indium(III)... 

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