Equilibration group 1 enolates

EXAMPLE 10.8 Enols, compounds with an OH group directly bonded to a vinyl carbon, are normally less stable than the corresponding carbonyl ( keto ) isomer. [A few enols (e.g., phenols) exist predominantly or exclusively in the end form.] Though the uncatalyzed equilibration of enols with their keto isomers is usually slow, the rate of isomerization increases dramatically in the presence of a small amount of acid (HA) or base (B) ... 

There are numerous base-solvent combinations that are capable of quantitatively converting even weakly acidic simple ketones into their enolate anions. However, in order to avoid aldol condensation and unwanted equilibration of enolates of unsymmetrical ketones during enolate formation, it is best to choose conditions under which the ketone, the base and the metal enolate are soluble. Likewise, solutions should be produced when indirect methods of enolate formation are employed. While certain metal cations such as Hg form a-metallated ketones, most of the metal cations in Groups 1, II and III exist as 0-metallated tautomers. - For organotin derivatives both the 0-metallated and C-metallated forms probably exist in equilibrium. ... 

If a Michael reaction uses an unsymmetrical ketone with two CH-groups of similar acidity, the enol or enolate is first prepared in pure form (p. llff.). To avoid equilibration one has to work at low temperatures. The reaction may then become slow, and it is advisable to further activate the carbon-carbon double bond. This may be achieved by the introduction of an extra electron-withdrawing silyl substituent at C-2 of an a -synthon. Treatment of the Michael adduct with base removes the silicon, and may lead as well to an aldol addition (G. Stork, 1973, 1974 B R.K. Boeckman, Jr., 1974). 

The aldehyde or ketone is called the keto form and the keto enol equilibration referred to as keto-enol isomerism or keto-enol tautomerism Tautomers are constitu tional isomers that equilibrate by migration of an atom or group and their equilibration IS called tautomerism The mechanism of keto-enol isomerism involves the sequence of proton transfers shown m Figure 9 6... 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

The equilibrium ratios of enolates for several ketone-enolate systems are also shown in Scheme 1.1. Equilibrium among the various enolates of a ketone can be established by the presence of an excess of ketone, which permits reversible proton transfer. Equilibration is also favored by the presence of dissociating additives such as HMPA. The composition of the equilibrium enolate mixture is usually more closely balanced than for kinetically controlled conditions. In general, the more highly substituted enolate is the preferred isomer, but if the alkyl groups are sufficiently branched as to interfere with solvation, there can be exceptions. This factor, along with CH3/CH3 steric repulsion, presumably accounts for the stability of the less-substituted enolate from 3-methyl-2-butanone (Entry 3). 

The abstraction of a proton a to a carbonyl group is not the only method for generating enolates and these alternative methods also offer possibilities for regio- and stereoselectivity. Thus, cleavage of silyl enol ethers (e.g., 1 and 3)9, 12 17 and enol acetates (e.g., 5)18 has been used for the generation of specific enolates. The conditions for these cleavages have to be chosen so that there is no equilibration of the lithium enolates formed. 

The acyclic, enolic compounds 7 and 9 may exist in either cis or trans forms. Methyl ethers of 7 have been isolated in the cis form,8 but it is not known whether the trans forms, which must be acyclic, exist. The relative proportion of isomers is controlled by the geometry of the parent sugar enediol. Although the acyclic forms are readily interconvertible tautomers, it appears that, in acidic medium, further reaction occurs much more rapidly than any equilibrating reactions. Compound 7 undergoes rapid elimination of a second hydroxyl group to give 11. This acyclic product, also, may exist as either a cis or a trans isomer, both forms of which have been isolated.8 The loss of a third molecule of water per molecule occurs after, or simultaneously with, the cyclization of 11 (see Section II, 3 p. 171), and results in formation of 5-(hydroxymethyl)-2-furaldehyde (5). 

Various groups have reported that additions of a-hetero substituted ester enolates to a,3-enones are temperature dependent, l40 c but, in general, the 1,2 to 1,4-equilibration of a-seleno and a-thio substituted ester adducts occurs at lower temperature than the a-oxo substituted ester adducts. In contrast to the simple ester enolates, the a-hetero substituted ester enolates are extremely useful for functionalization of alicyclic a,(3-enones with the tandem conjugate addition-electrophile trapping protocol, as shown... 

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