Enolates and their Equivalents

Enolates and their Equivalents. The generation of regiospecific enolates is another problem of considerable synthetic importance. Use of lithium bis(2-propyl)amide as base at low temperature is recommended - for formation of trilithio derivatives of 2,4,6-triketones and for synthesis with little loss of optical activity of the enolate of (14). The highly hindered base (15) is even better for carrying out in situ crossed aldol reactions between methyl ketones and aldehydes. 

The alternative approach involves generation of an enolate equivalent, and lithiated dialkylhydrazones (16) show considerable promise from this point of view. Unsymmetrical dimethylhydrazones (DMH s) are lithiated with notable regioselectivity and the products are readily converted into ketones by oxidative hydrolysis with NaI04. Furthermore, use of optically active hydrazones (17) allows a very respectable level of asymmetric induction at the new chiral centre. DMH s 

Wiaux-Zamar, J.-P. Dejonghe, L. Ghosez, J. F. Normant, and J. Villieras, Angew. Chem. 

Kuwajima, T. Sato, M. Arai, and N. Minami, Tetrahedron Letters, 1976, 1817. 

Lithiated oxazolines (22) are asymmetric carboxylic acid enolate equivalents, allowing quite reasonable optical induction in many cases. Organolithium reagents add to vinyloxazolines such as (23) [obtained by reaction of (22 R = H) with 3-methoxypropanal], and this approach has been applied to the synthesis of chiral lactones.  

---

We have considered the reactions of enolates and their equivalents with alkyl halides. In the next chapter we move on to consider the reactions of the same types of enolate equivalents with a different class of electrophiles carbonyl compounds themselves. 

How enolates and their equivalents react with alkylating agents ch26... 

Carbon-carbon bond formation is a reaction of fundamental importance to the cellular metabolism of all living systems and includes alkylation reactions involving one and five carbon fragments as well as carboxylation reactions. In addition, a very common method of generating carbon-carbon bonds in biology includes the reactions of enolates and their equivalents (such as enamines) with aldehydes, ketones, keto acids, and esters. Reactions in which the enolate derives from an acyl thioester are Claisen condensations, whereas the remainder are classified as aldol reactions. 

Copper(I)-Catalyzed Asymmetric Addition of Enolates and Their Equivalents... 173... 

Silyl enol ethers (Figure Si3.1) are stable molecules which may be isolated, purified, and characterized using standard organic procedures. As will be illustrated below, they are sources of regiochemically-pure enolate ions and their equivalents, and as such they play an important role in modern synthetic organic chemistry. 

Enol silyl ethers undergo aldol reactions with aldehydes, acetals and their equivalents with the aid of a Lewis acid catalyst. These reactions are discussed in Volumes 2-4. Enol silyl ethers prepared by hydro-silylation of a, 3-unsaturated ketones with a rhodium catalyst can be used for aldol reactions with aldehydes or ketones in situ under neutral conditions (equation 60)." ... 

In addition to aldehydes and ketones, acetals, ketals, orthoesters," a-halo ethers, a-halo sulfides, amino acetals and their equivalents also react with enol silyl ethers in the presence of Lewis acid to af-... 

Preparation and chemical reactivity of 2-chromanols 13ARK(1)101. Reactions of salicylaldehyde and enolates or their equivalents Versatile synthetic routes to chromane derivatives 12BJ02166. 

Conjugate additions of enolates or their equivalents to enones are also catalyzed by Lewis acids, and again enantioselective versions of the reactions have proved to be very useful (Figure 23.11). 

Although enolates, their equivalents, and otherwise stabilized carbanions would be interesting candidates for ARO of weso-epoxides, no efficient catalytic method has been developed to date. Crotti reported that 20 mol% of (salen)Cr-Cl complex 2 promoted the addition of the lithium enolate of acetophenone to cyclohexene oxide with moderate ees (Scheme 7.26) [50], However, the very low yields obtained... 

Carbonyl compounds can react with electrophiles via their enol isomers or equivalents, and these reactions result in a-substitution. 

Inter- and intramolecular reactions between a propargyiic carbocation equivalent stabilized by Co2(CO)6-coordination and enol derivatives also provide a good method for the carbon-carbon bond formation at the propargyiic carbon of propargyiic alcohols and their derivatives. Many diastereoselective and enantioselective propargyiic alkylation reactions at the propargyiic position take place between chiral propargyiic cation equivalents and enol derivatives. 

The conjugate addition of unstabilized enolates to various acceptors was conceptually recognized by early researchers however, complications were encountered depending on the enolates and acceptors employed. Reexamination of this strategy was made possible by the development of techniques for kinetic enolate formation. This discussion is divided into three enolate classes (a) aldehyde and ketone enolates, azaenolates or equivalents, (b) ester and amide enolates, dithioenolates and dienolates and (c) a,0-carboxylic dianions and a-nitrile anions, in order to emphasize the differential reactivity of various enolates with various acceptors."7 The a-nitrile anions are included because of their equivalence to the hypothetical a-carboxylic acid anion. 

The ring closure of 1,5-keto-acids and their derivatives is a widely used strategy for the synthesis of 2A-pyran-2-ones <1984CHEC, 1996CHEC-II>. The 1,5-keto acid derivatives are typically formed in situ with concomitant ring closure to form 2//-pyran-2-ones. There are three main approaches to access the prerequisite 1,5-keto acid derivatives, namely (i) reaction of an ester enolate with a 2-acyl vinyl cation equivalent, (ii) the reaction of a ketone enolate... 

In contrast to 83 and 85, 1,2-dimethyl-4,5-dihydroimidazole (89, n = 2) and 1,2-dimethyl- 1,4,5,6-tetrahydropyrimidine (89, n = 3) underwent direct acylation with two equivalents of aroyl chloride to give diacylenediamines 90 rather than enol benzoates. Their acid hydrolysis with sulfuric acid at water bath temperatures results in cleavage of one of the aroyl groups and benzoyl-substituted 1,1-enediamines 91 are formed in moderate yields (equation 31)103. 

Two transformations require special note because of their very high potential in organic synthesis. First, the use of allylic alcohols as substrates has been shown to result in /3-hydride elimination toward the OH group, and the resulting enol tautomerizes to the aldehyde. This overall conversion, illustrated for 2-methaUyl alcohol and 1-bromobutene, opens a new strategy for the synthesis of carbonyl-containing compounds, and is equivalent (with very different selectivities)... 

The Claisen rearrangement of allyl vinyl ethers 480 is a fairly general method for the preparation of y, -unsaturated carbonyl compounds of the general formula 481 from simple precursors (Scheme 2.154). ° Synthetically, this transformation is equivalent to the well-known a-allylation of enolates, which gives ultimately the same product. However, the mechanisms and conditions of these two reactions differ and their synthetic potentials are complementary to each other. 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

---