Enols/enolates chemistry

Enolate chemistry follows from this anion acting as a carbon nucleophile. 

Enolate chemistry is often the chemistry of the enolate salts. 

Show how by using regioselective enolate chemistry and organoselenium reagents, you could convert 2-phenylcyclohexanone to either 2-phenyl-2-cyclohexen-l-one or 6-phenyl-2-cyclohexen-l-one. 

Diaza compound 669 condensed with bromobutyryl chloride under classical basic conditions gives bicyclic derivative 670. This compound can be further functionalized, for example, via classical enolate chemistry (Scheme 110)... 

A new piperidine alkaloid Adalinine 352 was prepared in racemic form, using a rearrangement as a key step (equation 134). Enolate chemistry allowed double a-alkylation of cyclopentanone, producing 350 after oxime formation. Rearrangement provided a clear conversion into the lactam 351, easily converted to racemic Adalinine 352. 

The D-ring of steroids has been cleaved frequently by a Beckmann fragmentation. Typical strategy uses enolate chemistry to introduce an oximino group at the a-carbonyl carbon. Reduction of the carbonyl (or addition of a carbanion) produces an a-hydroxy oxime which serves as good substrate for the fragmentation. Two examples of this strategy are shown in equations 213 and 214. 

Show how, using enolate chemistry and organoselenium reagents, you could convert... 

The carbanion generated by ot-proton abstraction of a 2-alkyloxazoline is capable of typical enolate chemistry. Thus, the carbanion was found to react with nitriles to give an enamine, with formate esters to give an aldehyde that can be trapped,with chiral sulfinate esters to give chiral sulfoxides,and with alkylating agents. A carbamate-protected aminomethyl chiral oxazoline was deprotonated and alkylated with diastereoselectivities up to 92% de. ... 

The next extension of preparatively useful ester enolate chemistry was the deconjugative a-alkylation of a./J-unsaturatcd esters20,21. A Michael addition of LDA was avoided by the use of one equivalent of HMPA21, which forms a non-nucleophilic complex with the former. The yields of the mono- and disubstituted products are all in the region of 90% 21,22. 

For the use of lithium and sodium bis(trimethyl-silyl)amide respectively in carbonyl enolate chemistry see Barton (reference 15). 

ElectrophiHc substitutions with carbon and hetero electrophiles a to the carbonyl group of aldehydes and ketones are among the most important synthetic operations. Such regio-, diastereo-, and enantioselective substitutions can be carried out efficiently with the SAMP/RAMP hydrazone methodology [3]. For cases where virtually complete asymmetric inductions could not be attained, an alternative approach based on a-silylated ketones 2 was developed [4]. They can be prepared easily from ketones 1 in high enantiomeric purity (ee > 98%) by asymmetric carbon silylation employing the SAMP/RAMP hydrazone method (Fig. 1.1.1). After the introduction of various electrophiles via classical enolate chemistry with excellent asymmetric inductions, the desired product ketones 3... 

J. S. Fruchart, G. Lippens, C. Kuhn, H. Gras-Masse and O. Melnyk, Solid-phase enolate chemistry investigated using HR-MAS NMR spectroscopy, J. Org. Chem., 2002,67, 526-532. 

Palladium enolate chemistry has been exploited to perform a range of catalytic enantioselective reactions on carbonyl substrates, including aldol, Michael, Mannich-type, and a-fluorination.154... 

In a general sense, the Reformatsky reaction can be taken as subsuming all enolate formations by oxidative addition of a metal or a low-valent metal salt into a carbon-halogen bond activated by a vicinal carbonyl group, followed by reaction of the enolates thus formed with an appropriate electrophile (Scheme 14.1).1-3 The insertion of metallic zinc into a-haloesters is the historically first and still most widely used form of this process,4 to which this chapter is confined. It is the mode of enolate formation that distinguishes the Reformatsky reaction from other fields of metal enolate chemistry. 

Diels-Alder [4+2] Diels-Alder with diimine Deallylation (see also Palladium chemistry Electrophilic addition Enolate chemistry Li enolate... 

The foregoing classification is of fundamental significance for the understanding of enolate chemistry. For every pair of C,H acid and base, one needs to know whether the combination effects quantitative or partial enolate formation. If deprotonation is only partial, then the unreacted substrate may represent an electrophile that can react with the enolate nucleophile. In such a case, it depends on the specific circumstances whether an enolate reacts with any remaining substrate or whether it reacts only with an added different electrophile. The occurrence of a reaction between enolate and unreacted substrate is avoided if the C,H acid is deprotonated completely with a stoichiometric amount of a sufficiently strong base. 

Alkaline earth metal amides have a unique place in enolate chemistry in light of the preceding discussion. Yet, amides without steric demand—from NaNH2 to UNIT,—also are usually not suitable for the formation of enolates, since their nucleophilicities exceed their basicities. On the other hand, the amides LTMP, LDA, and LiHMDS (structures in Figure 4.18) are so bulky that they can never act as nucleophiles and always deprotonate C,H acids to the respective enolates. 

C. H. Heathcock, Modem Enolate Chemistry Regio- and Stereoselective Formation of Enolates and the Consequence of Enolate Configuration on Subsequent Reactions, in Modem Synthetic Methods (R. Scheffold, Ed.), Vol. 6, 1, Verlag Helvetica ChimicaActa, Basel, Switzerland, 1992. 

This chapter is also the last chapter in the second cycle of chapters within this book, with which we complete our survey of the important elementary types of organic reactions. We follow it with two review chapters, before looking in more detail at enolate chemistry and how to make molecules. 

---