Enols reactions, summary

Introduction The extended enolate problem Kinetic and thermodynamic control Wittig and Horner-Wadsworth-Emmons Reactions Extended Aza-Enolates Extended Lithium Enolates of Aldehydes Summary a-Alkylation of Extended Enolates Reaction in the y-Position Extended Enolates from Unsaturated Ketones Diels-Alder Reactions Extended Enolates from Birch Reductions The Baylis-Hillman Reaction The Synthesis of Mniopetal F... 

The study aids for this chapter include key terms and concepts (which are highlighted in bold, blue text within the chapter and defined in the Glossary (at the back of the book) and have hyperlinked definitions in the accompanying WileyPLUS course (www.wileyplus.com), the list of reaction types in Section 19.9, and the Summary of Mechanisms scheme for Enolate Reactions with Carbonyl Electrophiles and Synthetic Connections Involving Enolates. 

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. 

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... 

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... 

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... 

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. 

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]. 

Hie scheme of retrosynthetic analysis retraces these steps in summary. The decision to use the ch reaction for the enone and to add a C02Et group to stabilize the enolate would be taken at of the analysis. 

Hydroxylation of sodium and potassium enolates side reaction with lithium Substrate controlled stereoselectivity asymmetric hydroxylation Asymmetric hydroxylation with camphor sultam derivatives Asymmetric synthesis of tetracycline precursors Synthesis of a calcium channel opening drug Asymmetric synthesis ofbuproprion Summary... 

In summary, insufficient data are available to decide whether enzymes that catalyze proton abstraction from carbon acids either need or are able to reduce the values of G int from those measured for nonenzymatic reactions. But the conclusion is inescapable these enzymes must significantly stabilize the enolate anion intermediate if the observed values of kct and the associated rate acceleration are to be understood. 

In summary, several factors determine the stereochemical outcome of aldol addition reactions. The diastereochemical preference of the syn or anti isomer is determined by the configuration of the enolate and the orientation of the aldehyde within the TS. Chirality in either reactant introduces another stereochemical influence. The use of chiral auxiliaries can promote high facial selectivity in the approach of the aldehyde and thus permit the preparation of enantiomerically enriched products. The same outcome can be achieved using chiral Lewis acids as reaction catalysts. 

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