Ketone enolates regioselective formation

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Ketone imine anions can also be alkylated. The prediction of the regioselectivity of lithioenamine formation is somewhat more complex than for the case of kinetic ketone enolate formation. One of the complicating factors is that there are two imine stereoisomers, each of which can give rise to two regioisomeric imine anions. The isomers in which the nitrogen substituent R is syn to the double bond are the more stable.114... 

The regioselective formation of a cw-hexalone containing a homonuclear diene which is useful for elaboration into ocddentalol [178] by the condensation of 4-methyl-3-cyclohexenone with methyl coumalate is rather surprising. It seems that C-3 of the cyclohexenone, under the influence of the ketone group (perhaps via the enol), prefers an acceptor role. 

Fig. 13.24. O-Phosphoryla-tion of a ketone enolate to afford an enol phosphonamide (see Figure 13.13, bottom row, regarding the regioselectivity of the enolate formation) ...

The reaetion of ketones (with the exception of methyl ethyl ketone) with 1 and diiso-propy lethyl amine (DPEA) leads to regioselective formation of alkcny loxy dialkoxy boranes. A methyl group is deprotonated with high selectivity. A group is deprotonated almost exclusively in the presence of a CHR, group to form the (Z)-enolate (equation 1). ... 

II. C-C BOND FORMATION BYa-SUBSTITUTION OF KETONE ENOLATES A. Control of Stereo- and Regioselectivity in Enolate Preparation... 

Regioselective formation of thermodynamic enolates (or their corresponding silyl enol ethers) can be accomplished by treatment of unsymmetrical ketones with KH, or with KH, t-BuMe2SiCl in the presence of HMPAA ... 

The original Mannich reaction is the acid-catalyzed aminomethylation of enohz-able ketones with non-enolizable aldehydes and ammonia, primary amines, or secondary amines, which involves nucleophilic addition of ketone enols to iminium salts generated in situ from the aldehydes and the nitrogen compounds [183]. This three-component coupling reaction provides a powerful tool for carbon-carbon bond formation and introduction of nitrogen functionality. The classical Mannich reaction has some drawbacks in reaction efficiency, regioselectivity, and appli-... 

If the electrophile is a vinyl triflate, it is essential to add LiCl to the reaction so that the chloride may displace triflate from the palladium o-complex. Transmetallation takes place with chloride on palladium but not with triflate. This famous example illustrates the similar regioselectivity of enol triflate formation from ketones to that of silyl enol ether formation discussed in chapter 3. Kinetic conditions give the less 198 and thermodynamic conditions the more highly substituted 195 triflate. 

This approach can use the inherent regioselectivity of silyl enol ether formation (chapter 3) using kinetic or thermodynamic enolisation. Hence kinetic enolisation of enones (chapter 11) occurs on the a side leading to 2-Me3SiO-butadienes such as 222. Epoxidation of this silyl enol ether gives the unstable silyloxy ketone 223 which can be desilylated by fluoride ion and hence transformed into the hydroxyketone 225 or acetoxy ketone 224. These transformations are useful because the hydroxy ketones can be unstable34 (see below). 

In many cases, the regioselectivity of the enolate addition (C-O vs C-C bond formation) is a problem [100]. In particular, the site-selective C-acylation of ketone enolates to form P-ketoesters is an important issue in total synthesis. 

The enantiomeric /1-hydroxy ketones are available in an analogous way using the corresponding enantiomeric borinates. The reaction is plagued by low regioselectivity in the formation of the boron enolates, except when R1 is phenyl or isobutyl53,57. 

A further improvement utilizes the compatibility of hindered lithium dialkylamides with TMSC1 at —78 °C. Deprotonation of ketones and esters with lithium dialkylamides in the presence of TMSC1 leads to enhanced selectivity (3) for the kinetically generated enolate. Lithium t-octyl-t-butyl-amide (4) appears to be superior to LDA for the regioselective generation of enolates and in the stereoselective formation of (E) enolates. 

Regioselectivity and Stereoselectivity in Enolate Formation from Ketones and Esters... 

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