Enolate anions, addition reactions stabilities

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

Many carbanionic nucleophiles that would be considered too hard to react as Michael donors can be made into effective reagents for conjugate addition reactions by appending resonance or inductively stabilizing groups to soften their intrinsic Lewis basicity. Such stabilized anionic Michael donors include enolates, alkylthio-substituted carbanions, ylides and nitro-substituted carbanions. 

The simultaneous use of urea, or thiourea [76] and DABCO catalyst was introduced by the Connon group for the addition of methyl acrylate and benzaldehyde [39]. The study revealed that, although both ureas and thioureas accelerated the reaction relative to the uncatalyzed process, urea was superior to thiourea in terms of stability and efficiency. Chiral thiourea derivatives may offer, however, superior enantioselectivity. It was postulated, that the catalysts operate mainly via a Zimmerman-Traxler-type transition state 69 for addition of the resulting enolate anion to the aldehyde (Scheme 5.15). 

Michael reaction (Section 23.10) the 1,4-addition reaction of a stabilized enolate anion such as that from a 1.3-diketone to an a,p-unsaturated carbonyl compound. 

Mechanism Because the Tr-electron systems of the two functional groups in a,p-unsaturated ketone are conjugated, the radical anion A formed by electron addition from a reducing metal is resonance stabilized. The usual fate of the A is protonation (or other electrophilic bonding) at the P-carbon atom. This creates an enoxy radical B which immediately accepts an electron to form an enolate anion C. Protonation or alkylation of this enolate species then gives a saturated ketone D or E, which may be isolated or further reduced depending on the reaction conditions (Scheme 6.33). 

While the addition/oxidation and the addition/protonation procedures are successful with ester enolates as well as more reactive carbon nucleophiles, the addition/acylation procedure requires more reactive anions and the addition of a polar aprotic solvent (HMPA has been used) to disfavor reversal of anion addition. Under these conditions, cyano-stabilized anions and ester enolates fail (simple alkylation of the carbanion), but cyanohydrin acetal anions are successful. The addition of a cyanohydrin acetal anion to l,4-dimethoxynaphthalene-Cr(CO)3 occnrs by kinetic control at C-/3 in THF/HMPA and leads to the O -diacetyl derivative after methyl iodide addition and hydrolysis of the cyanohydrin acetal. Monoacylation of 1,4-dimethoxynaphthalene-Cr(CO)3 has been achieved nsing the seqnence of reactions shown in eqnation (126). ... 

Reversibility, even at low temperatures, has been shown to be fast for stabilized carbanions (e.g., nitrile stabilized carbanions, ester enolates) whereas (most) sulfur stabilized carbanions and simple organo lithium compounds add irreversibly. Nevertheless protonation is more rapid than anion dissociation even for the first category of anions mentioned and nucleophile addition/proto-nation reactions allows efficient conversion to a dearomatized product. 

As you study this mechanism, note how closely its first two steps resemble the first steps of the aldol reaction (Section 15.1). In each reaction, base removes a proton from an a-carbon in Step 1 to form a resonance-stabilized enolate anion. In Step 2, the enolate anion attacks the carbonyl carbon of another ester molecule to form a tetrahedral carbonyl addition intermediate. 

This chapter will discuss carbanion-like reactions that utilize enolate anions. The acid-base reactions used to form enolate anions will be discussed. Formation of enolate anions from aldehyde, ketones, and esters will lead to substitution reactions, acyl addition reactions, and acyl substitution reactions. Several classical named reactions that arise from these three fundamental reactions of enolate anions are presented. In addition, phosphonium salts wiU be prepared from alkyl halides and converted to ylids, which react with aldehydes or ketones to form alkenes. These ylids are treated as phosphorus-stabilized car-banions in terms of their reactivity. 

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