Enolates attack

Route (b) offers a short cut since the reaction between (5) and PhCHO under dehydrating conditions needs no control as (3) is the only possible enone from a ketone enolate attacking the more reactive aldehyde (p T 167). The Michael reaction is also better by this route as explained on p T 171, This is the published synthesis. 

Potassium tert-butoxide reacts with copper iodide to generate a copper / -butoxide species 98 (Scheme 29). Activation of the alkyne 94 by this copper catalyst (intermediate 96) allows the enolate attack to afford the cyclic... 

The Nl-Cl 1 bond is easily made first. Cleavage of the Cl 1-012 bond gives an iminium ion that is also a l,5-(hetero)diene. The Cope rearrangement occurs to give a new iminium ion and an enol. Attack of the enol on the iminium ion (the Mannich reaction) affords the product. 

The above experimental results strongly support a ligand-coupling mechanism [62, 63] for bismuth(V)-assisted a-alkenylation. Thus, the enolate attacks the... 

This enolate attacks compound 9 at the aldehyde carbon atom... 

Using electrospray ionization mass spectrometry in both positive and negative ion modes, the on-line scanning of the Morita-Baylis-Hillman reaction in the presence of imidazolium ionic liquids has been investigated. The interception of several supramolecular species indicated that ionic liquids co-catalyse the reactions by activating the aldehyde toward nucleophilic enolate attack and by stabilizing the zwitterionic species that act as the main intermediates.175... 

The enol attacks a protonated carbonyl group of a second ketone molecule. 

A plausible mechanism for this reaction is shown in Scheme 8. The nucleophilic attack of the enolate 13 occurs at the 4-position of pyridone 1 to form an adduct intermediate 15, and then regenerated enolate attacks at the 6-position, leading to bicyclic intermediate 16. The order of these nucleophilic attacks is not a serious problem because the same product is obtained even though the 6-position is attacked prior to the 4-position. The following elimination of anionic nitroacetamide from 16 affords RTF product, nitrophenol 14. 

Vinyl epoxides can also be ring-opened via an Sn2 sense, as exemplified in the macrocyclization of the epoxy-tethered cyclopentenone 76, which was induced to occur by treatment with lithium 2,2,6,6-tetramethylpiperidide (LTMP) followed by the mild Lewis acid diethylaluminum chloride in THF. The enolate attacked exclusively from the a-position of the... 

In drawing mechanisms, you can show either resonance form of an enolate attacking the electrophile. 

Aldol condensations also take place under acidic conditions. The enol serves as a weak nucleophile to attack an activated (protonated) carbonyl group. As an example, consider the acid-catalyzed aldol condensation of acetaldehyde. The first step is formation of the enol by the acid-catalyzed keto-enol tautomerism, as discussed earlier. The enol attacks the protonated carbonyl of another acetaldehyde molecule. Loss of the enol proton gives the aldol product. 

Crossed Claisen condensations between ketones and esters are also possible. Ketones are more acidic than esters, and the ketone component is more likely to deprotonate and serve as the enolate component in the condensation. The ketone enolate attacks the ester, which undergoes nucleophilic acyl substitution and thereby acylates the ketone. 

Chapters 26-29 continue the theme of synthesis that started with Chapter 24 and will end with Chapter 30. This group of four chapters introduces the main C-C bond-forming reactions of enols and enolates. We develop the chemistry of Chapter 21 with a discussion of enols and enolates attacking to alkylating agents (Chapter 26), aldehydes and ketones (Chapter 27), acylating agents (Chapter 28), and electrophilic alkenes (Chapter 29). 

The first step of the Wittig reaction proper is just like an aldol reaction as it consists of an enolate attacking an electrophilic carbonyl compound. But, instead of forming an aldol product, this adduct goes on to form an unsaturated carbonyl compound directly. 

In each reaction the only possible enolate attacks another molecule of formaldehyde. By now you have got the idea so we simply draw the next enolate and the structure of the third aldol. 

After protection of the OH group, treatment with base closes a three-membered ring to give a remarkably strained molecule. The ketone forms an enolate and the enolate attacks the alkyl bromide intramolecularly to close the third ring. This enolate is in just the right position to attack the C-Br bond from the back, precisely because of the folding of the molecule. 

The Claisen ester condensation involves the only possible enolate attacking the only possible electrophilic carbonyl group. The stereochemistry of the ring junction cannot be changed by the reaction, and the two ester groups that started tram must end up trans in the product. 

The mechanistic proposal for the formation of these p-laclonc products is related to that for the formation of y-lactones (Scheme 17). Initial formation of the conjugate enamine Ila is followed by a proton transfer from oxygen to carbon thereby forming the enolate V. In an aldol-type reaction this enolate attacks the electrophilic ketone providing zwitte-rions VI. The subsequent cyclization to the lac tone 18 then liberates the NHC catalyst. 

Have the enolate attack the electrophilic carbonyl of the second molecule. 

Prior to 2001, when the first serious computational approaches to the problem appeared in print, four mechanistic proposals had been offered for understanding the Hajos-Parrish-Wiechert-Eder-Sauer reaction (Scheme 6.8). Hajos and Parrish proposed the first two mechanisms Mechanisms A and B. Mechanism A is a nucleophilic substitution reaction where the terminal enol attacks the carbinolamine center, displacing proUne. The other three mechanisms start from an enamine intermediate. Mechanism B invokes an enaminium intermediate, which undergoes C-C formation with proton transfer from the aminium group. Mechanism C, proposed by Agamii to account for the nonlinear proline result, has the proton transfer assisted by the second proline molecule. Lastly, Mechanism D, proffered by Jung, proposed that the proton transfer that accompanies C-C bond formation is facilitated by the carboxylic acid group of proline. 

The authors proposed an intermediate complex 150 in which the chiral induction occurs by reaction of the scandium ketone enolate with the a, S-unsaturated ketone 148 (equation 42). The absolute configuration of the Michael adduct 150a can be explained by coordination of the hydroxy groups of 149 to Sc + in a tetradentate manner and shielding of the si-facc of the scandium enolate by an adjacent f-butyl group. Therefore, the enolate attacks the Michael acceptor preferably at the re-face. ... 

Nucleophilic attack The nucleophilic enolate attacks the alkyl halide, displacing the halide (a good leaving group) and forming the alkylation product by an 8 2 reaction. 

In Step [2], the nucleophilic enolate attacks the electrophilic carbonyl carbon of another molecule of aldehyde, thus forming a new carbon-carbon bond. This joins the a carbon of one aldehyde to the carbonyl c arbon of a second aldehyde. 

The enone could form an enolate on the methyl group (kinetic) or a more stable extended enolate, removal of a proton from the far end (y) of the molecule. Evidently, this is what happens here and extended enolate attacks at the first carbon along the chain (a) to add one cyanoethyl group. Repetic-adds the second cyanoethyl group and blocks the a position against any further enolate formation... 

Hydrolysis of the acetal releases an aldehyde and Mannich-style condensation leads to the produ The cyclization step in which the enol attacks the iminium ion is endo in both components (6-eni.i . trig for both the electrophile and the nucleophile) and thus difficult to do. However, by folding > molecule in a chair (frame in margin) a reasonable overlap between the required p orbital i possible. 

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