Enolate compounds allylic derivatives

Nucleophiles such as enolates or substituted allylmetal compounds are known to react with prochiral aldehydes and ketones to form mixtures of threo or erythro adducts. In case of aldehydes, high degrees of diastereoselection have been achieved 48 91,108). In the following three Sections, reactions of titanium and zirconium enolates as well as allyl derivatives are presented. 

Negishi, E.-i. Palladium-catalyzed cross-coupling involving 3-hetero-substituted compounds. Palladium-catalyzed a-substitution reactions of enolates and related derivatives other than the Tsuji-Trost allylation reaction. Handbook of Organopalladium Chemistry for Organic Synthesis 2002, 1, 693-719. 

Just as anions of allyl derivatives can be homoenolate equivalents (chapter 13) so anions of vinyl derivatives can be acyl anion equivalents. Vinyl (or enol) ethers can be lithiated reasonably easily, especially when there is no possibility of forming an allyl derivative, as with the simplest compound 81. The most acidic proton is the one marked and the vinyl-lithium derivative 82 reacts with electrophiles to give the enol ether of the product17 84. However, tertiary butyl lithium is needed and compounds with y-CHs usually end up as the chelated allyl-lithium 85. These vinyl-lithium compounds add directly to conjugated systems but the cuprates will do conjugate addition.18... 

Different from their previous reports, Hashimoto and co-workers developed a novel reaction in 2009. They found that allylic C—H bond amina-tion reaction occurs when silyl enol ether 120 derived from cyclohexanone is used. This interesting insertion reaction is ascribed to the fact that silyl enol ether 120 can just be -shaped. On the other hand, when Z-shaped silyl enol ethers 118 were employed (Scheme 1.43, top), the aziridination reactions occurred under similar conditions. After treating with trifluoroacetic acid, the a-aminated carbonyl products 119 were obtained in high levels of enan-tioselectivity. Starting from the p-aminated carbonyl compound 121, they accomplished the formal synthesis of (-)-pancracine (Scheme 1.43, bottom). 

Titanium tetrachloride is a moisture-sensitive, highly flammable liquid reacting violently with water (34). It is a strong Lewis acid capable of promoting Diels-Alder reactions (35) and induces the addition of silyl enol ethers and allyl silanes to carbonyl compounds and derivatives (34r-36). It is a less commonly used catalyst in Friedel-Crafts reactions but very useful for the acylation of activated alkenes and in the Fries rearrangement. 

V.2.1.4 Palladium-Catalyzed Allylation and Related Substitution Reactions of Enolates and Related Derivatives of Ordinary Ketones, Aldehydes, and Other Carbonyl Compounds... 

Through a short sequence of functional group manipulations, compound 6 could be elaborated from allylic alcohol 7, the projected product of a Wharton fragmentation4 of epoxy ketone 8 (vide infra). In turn, compound 8 could be derived from enone 9. In the synthetic direction, a Michael addition5 of hydroperoxide anion to enone 9 would be expected to take place from the less hindered side of the molecule. Epoxy ketone 8 would fhen form upon collapse of the intermediate enolate with concomitant expulsion of hydroxide ion (see arrows, Scheme 2). 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Another example of a [2s+2sh-1c+1co] cycloaddition reaction was observed by Barluenga et al. in the sequential coupling reaction of a Fischer carbene complex, a ketone enolate and allylmagnesium bromide [120]. This reaction produces cyclopentanol derivatives in a [2S+2SH-1C] cycloaddition process when -substituted lithium enolates are used (see Sect. 3.1). However, the analogous reaction with /J-unsubstituted lithium enolates leads to the diastereoselective synthesis of 1,3,3,5-tetrasubstituted cyclohexane- 1,4-diols. The ring skeleton of these compounds combines the carbene ligand, the enolate framework, two carbons of the allyl unit and a carbonyl ligand. Overall, the process can be considered as a for-... 

Acylation of the nitronate 9-71 leads to the iminium ion 9-72 which, by the addition of an isocyanide, forms the cation 9-73. Following two acyl group migrations, the compound 9-75 is obtained via 9-74. The best results were obtained when allylic nitro derivatives were used, as these can form the corresponding enolate in the presence of NEt3. Aliphatic nitro compounds could also be employed, but in these cases it was necessary to use the more basic DBU. 

Titanium tetrachloride-catalysed Michael additions of trimethylsilyl enol ethers to artemisitene afforded a neat route to 14-substituted artemisinin derivatives of type 125 (eg. R = allyl) and to 9-epiartemisinin derivatives 126 some of these compounds were more active against Plasmodium falciparum than artemisinin <00BMCL1601>. A series of 11-azaartemisinins also have better activity than artemisinin <00BMC1111>. On the other hand, epiartemisinin, prepared by base-catalysed epimerisation of artemisinin, has been shown to have poor antimalarial activity <00HCA1239>. 

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

It is only since the early 1980s that significant progress has been made with aldol reactions. This chapter introduces some of the most important developments on the addition of metallic enolates and the more important of the related allylic metal derivatives to carbonyl compounds. These processes are depicted as paths A and B in Scheme 3-1. 

The same strategy has been used by Williams (90JA808) in his synthesis of brevianamide B. The aldehyde (82), prepared enantioselectively from L-proline, was converted to the silyl ether. Acylation of this (BuLi, ClC02Me) gave the carbomethoxy derivative as a mixture of diastereo-mers, which was alkylated by gramine. As before, an enolate alkylation (Sn2 ) on an allyl chloride derived from the above gave the tricyclic compound, which could be transformed to brevianamide B (Scheme 24). 

Similarly, tetrahydropyrans 189, containing the all-cis substitution pattern could be easily synthesized by using the Z-enol carbamate 188, the geometric isomer of 181. Such a compound was readily prepared by applying the modified allyl-metallation protocol reported by Hoppe to the carbamate derivative 187 (Scheme 13.66) [83-85],... 

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