Allylation of carbonyl compounds

39 Other G-C bond forming reactions involving boronic acids (esters). 

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Mediated by Tin. In 1983, Nokami et al. observed an acceleration of the reaction rate during the allylation of carbonyl compounds with diallyltin dibromide in ether through the addition of water to the reaction mixture.74 In one case, by the use of a 1 1 mixture of ether/water as solvent, benzaldehyde was allylated in 75% yield in 1.5 h, while the same reaction gave only less than 50% yield in a variety of other organic solvents such as ether, benzene, or ethyl acetate, even after a reaction time of 10 h. The reaction was equally successful with a combination of allyl bromide, tin metal, and a catalytic amount of hydrobromic acid. In the latter case, the addition of metallic aluminum powder or foil to the reaction mixture dramatically improved the yield of the product. The use of allyl chloride for such a reaction,... 

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... 

Regio- and Stereoselectivity. For the allylation of carbonyl compounds mediated by indium and other compounds in aqueous media, usually the carbon-carbon bond forms at the more substituted carbon of the allyl halide, irrespective of the position of halogen in the starting material. However, the carbon-carbon bond forms at the less-substituted carbon when the y-substituents of allyl halides are large enough (e.g., trimethylsilyl or tert-butyl) as shown by Chan et al.139 (Scheme 8.10). The following conclusions can be drawn ... 

Palladium catalyzes allylation of carbonyl compounds with various ally lie compounds using In-InCl3 in aqueous media (Eq. 8.66).158 Various allylic compounds can be effectively applied via the formation of TT-allylpalladium(II) intermediates and their transmetalation with indium in the presence of indium trichloride in aqueous media. 

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). 

Nickel-Catalyzed Reductive Allylation of Carbonyl Compounds with 1,3-Dienes... 

Tin compounds can be produced by the Nalco-type reactions39 as well as by Cd and Zn mediated methods42,43. The use of organotin compounds in electrodically induced transmetallations has also been described in a study in which Grignard-type allylation of carbonyl compounds has been carried out by electrochemically recycled allyltin reagents44. 

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 Grignard-type allylation of carbonyl compounds has been performed in an... 

Scheme 149 Tin-mediated reductive allylation of carbonyl compounds.

Scheme 150 Barbier-type allylation of carbonyl compounds with electrogenerated lead(0).

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]. 

Two main types of processes which belong to basic synthetic reactions have been investigated recently the allylation of carbonyl compounds and the Refor-matsky reaction. 

Scheme 5. Regioselectivity in the Pd-catalyzed allylation of carbonyl compounds in the presence of Zn salts...

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)... 

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. 

Stereo specific generation and reactions of allylic alkali and alkaline earth metals have been reviewed121 and solvent-mediated allylation of carbonyl compounds with allylstannanes has been explored.122 Chiral phosphoramides derived from (5 )-proliiie have been used to catalyse asymmetric allylation of aromatic aldehydes by allylic trichlorosilanes.123... 

The allylation of carbonyl compounds with allyltin reagents is still an active area of organotin chemistry from the methodological point of view, and also for synthetic applications. For completeness we should add several alternative techniques, such as the development of trifluoromethanesulphonic acid as a Bronsted acid catalyst for the allylation of aldehydes in water123, or the design of fluorous allyltin reagents for the platinum-catalysed allylation of aldehydes124. 

Unfortunately, substitution in the y-position, such as in crotyltin, led to poorly reactive allyltins, due to the decrease in the addition rate of the radicals to the double bond. It has been established that, generally, the competitive allylic hydrogen abstraction became predominant, destroying the crotyltin reagent548. The use of y-substituted allyltins for the photo-induced radical allylation of carbonyl compounds represents an interesting... 

The chemistry of asymmetric allylation of carbonyl compounds has further progressed since the review in Comprehensive Asymmetric Catalysis [1] and plenty of papers including reviews [2,3] on chiral catalysts for the reaction have since appeared. This chapter describes new examples of catalytic enantioselec-tive allylation of carbonyl compounds with allylmetals in the presence of a catalytic amount of chiral Lewis acid or chiral Lewis base (Scheme 1). Compounds 1-36 [4-49] shown in Fig. 1 are the chiral catalysts reported since 1998, which have been used in the asymmetric allylation or propargylation of carbonyl compounds. Chiral compounds 37-40 [50-53], which have been utilized in the stoichiometric version, are also candidates for the chiral catalyst (Fig. 2). 

The effectiveness of various substituted BINOL ligands 12-16 in the Zr(IV)-or Ti(IV)-catalyzed enantioselective addition of allyltributyltin to aldehydes was also investigated by Spada and Umani-Ronchi [21], The number of noteworthy examples of asymmetric allylation of carbonyl compounds utilizing optically active catalysts of late transition metal complexes has increased since 1999. Chiral bis(oxazolinyl)phenyl rhodium(III) complex 17, developed by Mo-toyama and Nishiyama, is an air-stable and water-tolerant asymmetric Lewis acid catalyst [23,24]. Condensation of allylic stannanes with aldehydes under the influence of this catalyst results in formation of nonracemic allylated adducts with up to 80% ee (Scheme 3). In the case of the 2-butenyl addition reac-... 

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. 

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