The Chemistry of Enols and Enamines

In six chapters we have dealt with the chemistry of molecules containing C=0 double bonds (Chapter 6-11). In this context we encountered 

Despite their diversity, the cited reactions share a common feature they take place on the carbonyl or carboxyl group. 

In the present—and next—chapter, the focus will once more be on the chemistry of molecules containing C=0 double bonds. However, Chapters 12 and 13 will for the first time deal with reactions taking place in the position next to the carbonyl or carboxyl group. They are known for both neutral derivatives of carbonyl or carboxyl compounds (Chapter 12) and their conjugate bases, i.e., the enolates (Chapter 13). The neutral derivatives of carbonyl or carboxyl compounds, that allow for reactions next to the C=0 double bond, are presented in the following scheme  

B ( enamine ) C ( enol ether ) D ( silyl enol ether ) E ( silyl ketene acetal ) 

Bruckner R (author), Harmata M (editor) In Organic Mechanisms — Reactions, Stereochemistry and Synthesis Chapter DOI 10.1007/978-3-642-03651-4 12, Springer-Verlag Berlin Heidelberg 2010 

---

In recent years The Chemistry of Functional Groups series has included three volumes on composite functional groups in which a C=C double bond was attached to another group. The chemistry of enones (edited by S. Patai and Z. Rappoport) appeared in 1989 The chemistry of enols (edited by Z. Rappoport) appeared in 1990 and The chemistry of enamines (edited by Z. Rappoport) appeared in 1994. We believe that the time has arrived for a book dealing with the combination of C=C double bonds, namely dienes and polyenes. The two double bonds can be conjugated, and conjugated dienes have a chemistry of their own, but even non-conjugated dienes show certain reactions that involve both double bonds. Allenes and cumulenes, which represent a different combination of the double bonds were treated in The chemistry ofketenes, allenes and related compounds, edited by S. Patai in 1980. 

This is painfully unlike the case of enols, wherein a tentative set of Benson increments has been developed [F. Turecek and Z. Havlas, J. Org. Chem., 51, 4066 (1986)]. This is not particularly surprising—the collection of thermochemically characterized classical and thus unburied enols is much more coherent than that of enamines [see J. P. Guthrie, in The Chemistry of Enols (Ed. Z. Rappoport), Wiley, Chichester, 1990]. The reader is addressed, however, to S. W. Slayden and J. F. Liebman, in Supplement E The Chemistry of Hydroxyl, Ether and Peroxide Groups, Vol. 2 (Ed. S. Patai), Wiley, Chichester, 1993, for a brief excursion into the complications that arise in the study of more general enols. 

For several tautomeric systems ketones/enols, imines/enamin and others) a distinct reversal of the stability order is observed when going from the neutral compounds to the radical cations, the first use of which in a new preparative a-Umpolung reaction has been documented for keto/enol systems. The present review provides a critical evaluation of the chemistry of enol radical cations in solution with a special emphasis on the Umpolung reaction and the intermediates thereof. Other enol type of radical cations are discussed with respect to their potential to provide a-carbonyl radical and a-carbonyl cation intermediates. Hence, this article does not constitute a comprehensive summary on all enol type of radical cation reactions. All potentials in this review are referenced versus SCE, unless noted otherwise. Potentials measured against the ferrocene/ferrocenium couple were converted to SCE by adding 0.334 V. 

See Patai, S. The Chemistry of the Carbonyl Group, Wiley, London, 1966 Rappoport, Z. The Chemistry of Enols, Wiley, NY, 1990 Patai, S. The Chemistry of the Thiol Group, Wiley, London, 1974 Zabicky, J. The Chemistry Amides, Wiley, London, 1970 Boyer, J. H. The Chemistry of the Nitro and Nitroso Groups, Interscience Publishers, NY, 1969 Patai, S. The Chemistry of Amino, Nitroso, Nitro Compounds and their Derivatives, Wiley, NY, 1982 Patai, S. The Chemistry of Amino, Nitroso, Nitro and Related Groups, Supplement F2,Wiley, Chichester, 1996 Cook, A. G. Enamines, 2nd ed., Marcel Dekker, NY,... 

This chapter introduced the use of enolates and/or enamines as nucleophiles in several reactions, including aldol reactions, Claisen condensations and Michael additions, alkylations, and acylations. We can also use LDA to generate the enolate anions and perform the same reactions, as shown here for cyclohexanone and a few specific electrophiles. Similar reactions are possible for aldehydes and esters with a-hydrogens. The synthetic versatility of this approach has made LDA a very popular and important reagent in modem synthetic organic chemistry. 

Gilbert stark was bom in Brussels and became an assistant professor of chemistry at Harvard In 1948. Since 1953, Stork has been at Columbia University In New York. Sfnce the 1950s, he has pioneered new synthetic methods, among them many involving. enolates and enamines. 

Recent developments in the chemistry of the 1,2-unsaturated cyclic compounds, namely, the glycals and the 2-hydroxyglycals, are included in order to supplement the earlier Chapters on these topics. There follows a discussion of other cyclic and acyclic sugars which possess, at various positions in the carbon chain, alkenyl, enolic, or enamine systems. The scope has been arbitrarily restricted by the exclusion of the ends themselves [and, therefore, of reductones and compoimds related directly to L-ascorbic acid (1)], of such enones as the pyrone derivative (2), and of dienes or dienones [for example, kojic acid (3)]. Cyclohexene derivatives... 

For both types of substituent, the effects are more marked on the more distant ( 3) proton. If these shifts rehect the true electron distribution, we should be able to deduce something about the chemistry of the following three compounds. You might expect that nucleophiles will attack the electron-deficient site in the nitroalkene, while electrophiles will be attacked by the electron-rich sites in silyl enol ethers and enamines. These are all important reagents and do indeed react as we predict, as you will see in later chapters. Look at the difference— there are nearly 3 ppm between the shifts of the same proton on the nitro compound and the enamine ... 

Carbon nucleophiles play a central role in organic chemistry, as they form the basis of carbon-carbon bond formation. A few are shown in Figure 1.2, including such carbanionic species as organolithiums (RLi), Grignard reagents (typically written as RMgBr), and the cyanide (CN ) and acetylide (R-C=C ) anions. Other examples such as enolates, enols, and enamines will be briefly discussed in Section 1.15. 

Carbon-carbon bond-forming reactions comprise the most important general class of synthetic transformations. Among the various methods used for the construction of these bonds, those based on electrophilic addition to eno-lates (and their analogs silyl ketene acetals, silyl enol ethers, enamines, azaenolates, etc.) are especially pervasive. Indeed, enolate chemistry has provided much of the foundation for the advancement of synthetic organic chemistry to its present state. Over the years, an enormous amount of effort has gone into the study of enolate chemistry. Much of this work has focused on the development of strategies for the asymmetric a-alkylation of monocarbonyl compounds. 

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

Donor- and acceptor-substituted allenes with general structures 1 or 2 (Scheme 8.1) have the most obvious synthetic potential among functionalized allene derivatives and therefore they serve as versatile building blocks in many synthetic endeavors [1], As expected, the reactivity of the double bonds of 1 or 2, which are directly connected to the activating substituents, are strongly influenced by these groups. Hence there is enol ether or enamine reactivity of 1 and Michael acceptor type chemistry of 2. In addition, the terminal double bonds are also influenced by these functional groups. 

While most of the work has been done commencing with the nickel(II) complex (51), the chemistry is quite general. The enamine complex (53) can be deprotonated on nitrogen to yield the neutral imine complex (55). Even the protons of the methyl group in the enol ether complex (52) are sufficiently acidic for the formation of the neutral complex (54). Both of these reactivity features occur together in the alkylation reaction shown in Scheme 18.126 The macrocyclic rings in complexes such as (52), (53) and especially the more flexible complex (56) are not planar but bowl-... 

This section describes the additions of stabilized carbon nucleophiles, such as cyanide, malonate, ketone enolates, enamines, etc., to alkenic ir-systems. These reactions are highly useful in organic synthesis since they are all carbon-carbon bond-forming reactions, and therefore have been used extensively in organic chemistry. 

---