Enolates summary

Any doubt about the existence of individual tautomers is now long past some tautomers can be crystallized separately (desmotropy), and others can be observed simultaneously in the same crystal (Section V,D,2) in summary, tautomers are not intrinsically different from isomers. Maybe it is worth mentioning that even two identical tautomers can differ. This is the case for the two intramolecular hydrogen-bonded (IMHB) enol tautomers of acetylacetone and for many NH-azoles they correspond to a doublewell profile for the proton transfer with both wells having the same energy (autotrope). 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

In summary, the same factors that operate in the electrophile, namely steric, chelation, and polar effects, govern facial selectivity for enolates. The choice of the Lewis acid can determine if the enolate reacts via a chelate. The final outcome depends upon the relative importance of these factors within the particular TS. 

Summary of Facial Stereoselectivity in Aldol and Mukaiyama Reactions. The examples provided in this section show that there are several approaches to controlling the facial selectivity of aldol additions and related reactions. The E- or Z-configuration of the enolate and the open, cyclic, or chelated nature of the TS are the departure points for prediction and analysis of stereoselectivity. The Lewis acid catalyst and the donor strength of potentially chelating ligands affect the structure of the TS. Whereas dialkyl boron enolates and BF3 complexes are tetracoordinate, titanium and tin can be... 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

In summary, boryl enolate 38 can be obtained via in situ O-borylation of N-propionylsultam 37 and converted to aldol product 40 upon treatment with aliphatic, aromatic, or a,/l-unsaturatcd aldehdyes at - 78°C in the presence of TiCU- As aldol product 40 can normally be obtained in crystalline form, in most cases diastereomerically pure anti- Ao 40 can also be obtained after the recrystallization. 

The existence of a protonated oxazolone has been demonstrated indirectly by a simple experiment. When p-nitrophenol was added to an excess of 2-alkoxy-5(4//)-oxazolone in dichloromethane, a yellow color appeared. The color persisted until all the p-nitrophenol had been consumed by the oxazolone. The anion of p-nitro-phenol is yellow. The explanation for the color of the mixture is the presence of the p-nitrophenoxide anion that was generated by abstraction of the proton by the oxazolone. In summary, protonation of the O-acylisourea suppresses the side reaction of oxazolone formation as well as the side reaction of A-acylurea formation and accelerates its consumption by enhancing its reactivity and generating an additional good nucleophile that consumes it. Protonation of the oxazolone suppresses epimerization by preventing its enolization and also increases the rate at which it is consumed.4 68 78 79... 

A summary of representative stereochemically defined metal enolates and their respective kinetic aldol condensations with benzaldehyde is provided in Table 24. Both the metal center and the enolate substituent Ri for the substituted carbonyl derivatives... 

In summary, enolates derived from 2-ketosugars may serve as progenitors to C-glycosides, but this topic is still at an early phase of its development and warrants more extensive investigation and evaluation. 

TABLE 25. Summary of bracketing (equation 38) and hydrogen/deuterium exchange (equation 39) experiments for thiocarbonyl enolate anions (R = H, Me)... 

The evidence is now practically conclusive that the intramolecular process occurs via hydrogen bonding between the gamma carbon atom and the oxygen, and that scission then occurs to give the enol form of a methyl ketone and the olefin in a single step. A very brief summary of the evidence which leads to this conclusion is as follows. 

In summary, a stereoselective 10-step total synthetic route to the antimalarial sesquiterpene (+)-artemisinin (1) was developed. Crucial elements of the approach included diastereoselective trimethylsilylanion addition to a,p-unsaturated aldehyde 16, and a tandem Claisen ester-enolate rearrangement-dianion alkylation to afford the diastereomerically pure erythro acid 41. Finally, acid 41 was converted in a one-pot procedure involving sequential treatment with ozone followed by wet acidic silica gel to effect a complex process of dioxetane formation, ketal deprotection, and multiple cyclization to the natural product (+)-artemisinin (1). The route was designed for the late incorporation of a carbon-14 label and the production of a variety of analogues for structure-activity-relationship (SAR) studies. We were successful in preparing two millimoles of l4C-l73 which was used for conversion to I4C-arteether for metabolism75 and mode of action studies.76,77... 

So what is new here We can save time, materials and effort if we combine two reactions in one operation. These tandem processes, as they are called, avoid the isolation of potentially difficult intermediates and may avoid the need for control over reactions in chapter 19 we discussed the need for control in the acylation of enolates. Workers at Merck1 combined the difficult acylation of enolates 7 by acid chlorides with the capture of the intermediates 9 by hydrazine to give stable pyrroles 10. This is a summary of their method ... 

A summary of reported reactions of enolate ions with alkynyliodonium salts is presented in Table 6. Those that result in alkynylation are denoted with an (A), while those that... 

Summary Enolate Additions and Condensations 1092 EssentialTerms 1094 Study Problems 1096... 

We end with a summary of the factors controlling the two modes of addition to a, ( -unsaturated carbonyl compounds, and by noting that conjugate addition will be back again—in Chapters 23 (where we consider electrophilic alkenes conjugated with groups other than C=0) and 29 (where the nucleophiles will be of a different class known as enolates). 

Summary ofthe last four sections on specific enol equivalents. 

First, chemoselective (Chapter 24) conjugate addition of the silyl ketene acetal on the enone is preferred to direct aldol reaction with the aldehyde. Then an aldol reaction of the intermediate silyl enol ether on the benzaldehyde follows. The stereoselectivity results, firstly, from attack of benzalde-hyde on the less hindered face of the intermediate silyl enol ether, which sets the two side chains trans on the cyclohexanone, and, secondly, from the intrinsic diastereoselectivity of the aldol reaction (this is treated in some detail in Chapter 34). This is a summary mechanism. 

In 1971 Kol tsov and Kheifets were the authors of a review of all type of tautomerism and this is a useful summary of the intensive efforts that went into tackling the problem in the 1950s and 1960s10). The keto e enol equilibrium has three features of interest... 

Maleic hydrazide has also been investigated in detail and its structure determined as the monohydroxymonooxo form, i.e., 6-hydroxy-3(2I )-pyridazinone, from spectroscopic data (for summary see Volume 1 of this Series, Chapter VII, p. 366). Similar conclusions were reached for substituted maleic hydrazides, although for 4- or 5-substituted maleic hydrazides it is not known which of the amide groups relative to the substituent is in the lactam and which in the enolized form. 

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. 

In summary, these data support the proposed overall mechanistic scheme for the a-Umpolung reaction (Scheme 8), which invokes rapid deprotonation of the enol radical cations 86Should the other mechanisms (Scheme 3, mech. 4 and 5) be valid for the a-Umpolung reaction of 86 one would expect the yields to go up with less electron rich enols, since both the benzyl radical ArCH -C(OH)(OMe)CH3 and the a-hydroxy radical ArCH(OMe)-C-(OH)CH3 should be readily oxidized even for a p-chloroaryl system. In competition experiments... 

In summary, the literature survey provides clear evidence for a-carbonyl radical intermediates but no convincing proof for further oxidation to a-carbonyl cation in the vast majority of silyl enol ether radical cation reactions. This suggests that for most cases, silyl enol ethers are more readily oxidized than the corresponding a-carbonyl radicals. Only in oxidations of -aryl substituted silyl enol ethers, a-carbonyl cation intermediates have been invoked. For example, one-electron oxidation of 87d with TTA" " in acetonitrile/MeOH afforded 76 in analogy to the a-Umpolung of ketones via enol radical cations (Scheme 4), and oxidation of 124 with FePHEN provided benzofuran 19 [171]. 

In summary, although the azidation of phosphorus-stabilized carbanions at the present time is not yet as stereoselective as azidation, especially of chiral imide enolates (see Section 7.1.1.), the Evans reagents2 also provide a promising methodology for the preparation of optically active a-aminophosphonic acids12. 

In summary, the electrophilic amination of lithium enolates derived from 1 with di-toT-buty] azodicarboxylate (DBAD) provides an excellent approach to the stereoselective synthesis of a-hydrazino and a-amino acids. 

This section provides a comprehensive tabular summary of mixed metal oxide deposition, complementary to the books edited by Rees Jr. and by Jones and O Brien, focusing on the literature dealing with metal enolate precursors published after 1996. 

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