Imines allylation reactions

Ally 1-tin compounds are employed as more reactive allylating agents. Because of their high reactivity, less active catalysts (TX species having mild Lewis acidity) or less reactive substrates are often required (Scheme 23).88,89 In addition to carbonyl compounds as substrates, allylation reactions of imines have been also reported.90 Also, a binuclear TiIV Lewis acid has been developed (compound (C) in Scheme 23), which shows higher catalytic activity than the mononuclear analogue (D) because of bidentate coordination to the carbonyl moiety of the substrate.91... 

In 2001, the preparation of allylytterbium bromide and the synthesis of homoallylic alcohols using allylytterbium bromide were reported.39 393 Ytterbium metal was found to be activated by a catalytic amount of Mel at 0 °C in THF to produce allylytterbium bromide 66 (Equation (11)). The allylation reaction of a wide range of aromatic aldehydes and ketones proceeded at ambient temperature or less in good to high yields (Table 2). Imines also reacted with allylytterbium bromide to afford homoallyl amines (Table 3). 

Besides the allylation reactions, imines can also undergo enol silyl ether addition as with carbonyl compounds. Carbon-carbon bond formation involving the addition of resonance-stabilized nucleophiles such as enols and enolates or enol ethers to iminium salt or imine can be referred to as a Mannich reaction, and this is one of the most important classes of reactions in organic synthesis.104... 

This chapter has introduced the aldol and related allylation reactions of carbonyl compounds, the allylation of imine compounds, and Mannich-type reactions. Double asymmetric synthesis creates two chiral centers in one step and is regarded as one of the most efficient synthetic strategies in organic synthesis. The aldol and related reactions discussed in this chapter are very important reactions in organic synthesis because the reaction products constitute the backbone of many important antibiotics, anticancer drugs, and other bioactive molecules. Indeed, study of the aldol reaction is still actively pursued in order to improve reaction conditions, enhance stereoselectivity, and widen the scope of applicability of this type of reaction. 

Grigg and co-workers described a novel three-component indium-palladium-mediated allylation reaction [67]. As exemplified by Eq. 14.16, 3,3-disubstituted oxi-ndole derivative 133 was obtained smoothly from phenyl iodide, the easily available isatin imine 132 and 1,2-propadiene (131). Excellent levels of diastereoselectivity were obtained in this cascade reaction employing imines derived from enantiopure sulfmamides. 

In 1998, Yamamoto et al. reported the first catalytic enantioselective allylation of imines with allyltributylstannane in the presence of a chiral 7i-allylpalladium complex 23 (Scheme 9) [15]. The imines derived from aromatic aldehydes underwent the allylation with high ee values. Unfortunately, the allylation reaction of aliphatic imines resulted in modest enantioselectivities. They proposed that a bis-Jt-allylpalladium complex is a reactive intermediate for the allylation and reacts with imines as a nucleophile. The bis-Jt-allylpalladium complex seemed the most likely candidate for the Stille coupling [16]. Indeed, the Stille coupling reaction takes place in the presence of triphenylphosphine even if imines are present, whereas the allylation of imines occurs in the absence of the phosphine [17]. They suggested the phosphine ligand played a key role in controlling the... 

Taylor and Blackburn proved64 that the in situ condensation of an aldehyde with an amine can be made to occur in an intermolecular fashion. Thus, treatment of primary allylic, propargylic and benzylic alcohols with active Mn02 in the presence of diverse primary amines and molecular sieves in boiling CH2C12 leads to the selective oxidation of the alcohols in the presence of the primary amines and to the formation of the corresponding imines by reaction of the alcohols with the intermediate aldehydes. 

Examples of imine allylation in aqueous media are rather limited compared with the carbonyl version. This is ascribed to the lower electrophilicity of the C=N function of imines and its ease of hydrolysis to carbonyl compounds. In order to overcome the undesired side-reactions, sulfonimines in place of simple imines are success-fully used for the allylation under aqueous conditions (Equation (61)). Grotylation of cr-sulfonimino esters gives... 

Sc(OTf)3 promoted allylation reactions of carbonyl compounds were reported, (a) Tetraallylger-manium T. Akiyama, J. Iwai, Tetrahedron Lett. 1997, 38, 853-856. (b) Allyltrimethylsilane V. K. Aggarwal, G. P. Vennall, Tetrahedron Lett. 1996,37, 3745-3746. Sc(OTf)3 is also an effective catalyst for the allylation of imines with allyltributyltin. (c) C. Bellucci, P. G. Cozzi, A. Umani-Ronchi, Tetrahedron Lett. 1995,36,7289-1292. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

The last class of allylation reactions that are amenable to asymmetric catalysis employs allylboronate derivatives. Schaus reported that several chiral BINOL deri vatives catalyze the enantioselective asymmetric allylboration of acyl imines [97]. This reaction is most effective when 3,3 diphenyl BINOL acts as the catalyst and allyldii sopropoxyborane is the nucleophile. The allylation products are obtained in good yields (75 94%) and excellent enantiomeric excesses (>90% ee) for both aromatic and aliphatic imines (Table 1.13). 

Pd-catalyzed umpolung allylation reactions of aldehydes, ketones, and imines... 

Compared with well-established electrophilic it-allylpalladium chemisty, the catalytic asymmetric reaction via umpolung of jt-allylpalladium has received very limited exploration [93]. Zhou and co-workers investigated the Pd-catalyzed asymmetric umpolung allylation reactions of aldehydes [22a, 94], activated ketones [95], and imines [96] by using chiral spiro ligands (5)-18e, (S)-17c, and (5)-17a, respectively. One representative example is that of the Pd/(5)-18e-catalyzed umpolung allylation of aldehydes with allylic alcohols and their derivatives, which provided synthetically useful homoallylic alcohols from readily available allylic alcohols, with high yields and excellent enantioselectivities (Scheme 33). 

The first example of truly catalytic, enantioselective allylation of imines has been reported by Yamamoto [46a]. These authors had first discovered that imines could undergo allylation reaction via a palladium-catalyzed allylstannane reaction to afford the corresponding homoallylamines in high yields [47a, 47b,... 

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