Nucleophiles enolate anions

The second complication arises if the alkyl compound reacts with both carbon and oxygen of the nucleophilic enolate anion. The carbon product is the result of C-alkylation, whereas the oxygen product is the result of O-alkylation ... 

Again the best approach is to identity the site where the nucleophilic enolate anion forms, the a-carbon with the most acidic hydrogen. This carbon becomes bonded to the carbonyl carbon of the ester electrophile in the final product. 

One aldehyde molecule reacts with base (OH ) at it is a C—H bond to give a nucleophilic enolate anion. 

Azirines react with enolate anions. Initial nucleophilic attack on phenyl 1-azirine by the enolate anion derived from acetophenone gives intermediate (223) which undergoes 1,2-bond cleavage, cyclization and hydroxyl group elimination to give pyrrole (226). 

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

Because enolate anions ffle sources of nucleophilic car bon, one potential use in organic synthesis is their- reaction with alkyl halides to give a-alkyl derivatives of aldehydes and ketones ... 

Compare atomic charges for the enolate anion and the lithium salt. Are there major differences, in particular, for the oxygen and the a carbon Also compare the highest-occupied molecular orbital (HOMO) in the two molecules. This identifies the most nucleophilic sites, that is, the most likely sites for attack by electrophiles. Are the two orbitals similar or do they differ substantially Elaborate. 

THF) at room temperature (Scheme 18) (95T8605). The proposed mechanism for this conversion involves the abstraction of H3 by basic attack of NaH to give an enolate anion, which, via ring opening, affords the 2(5//)-furanone 61 by a straightforward intramolecular nucleophilic acyl substitution (Scheme 18) (95T8605). 

The next step is the nucleophilic addition of the enolate anion 5 to the carbonyl group of another, non-enolized, aldehyde molecule 2. The product which is obtained after workup is a /3-hydroxy aldehyde or ketone 3 ... 

Posner recently reported a very simple and fast way to activate epoxides towards nucleophilic opening by ketone lithium enolate anions by use of BF3 Et20 (1 equiv.) [73]. The application of this procedure to the nucleophilic opening of propene oxide with the lithium enolate of 2-cycloheptanone, obtained by the conjugate addition of trimethylstannyllithium to 2-cycloheptenone, afforded the stan-... 

Vinyl sulfones, being good Michael acceptors, have been regarded as useful reagents for carbon-carbon bond formation. Nucleophiles used often are organometallic reagents, enamines and enolate anions and the Michael addition products are usually obtained in... 

The SET mechanism is chiefly found where X = I or NO2 (see 10-104). A closely related mechanism, the SrnE takes place with aromatic substrates (Chapter 13). In that mechanism the initial attack is by an electron donor, rather than a nucleophile. The Srn 1 mechanism has also been invoked for reactions of enolate anions with 2-iodobicyclo[4.1.0]heptane. An example is the reaction of l-iodobicyclo[2.2.1]-heptane (15) with NaSnMe3 or LiPPh2, and some other nucleophiles, to give the substitution product. Another is the reaction of bromo 4-bromoacetophenone (16) with Bu4NBr in cumene. " The two mechanisms, Sn2 versus SET have been compared and contrasted. There are also reactions where it is reported that radical, carbanion, and carbene pathways occur simultaneously. ... 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

Participation by the enolate anion could, in principle, act via either the anionic carbon or oxygen. The former, however, is known to be considerably the more nucleophilic centre. The latter would give rise to a lactone, which would be rapidly hydrolysed under the usual conditions of excess base to give the identical final product. There is no evidence for the occurrence of such a process. 

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

The proportion of the /rans-O-alkylated product [101] increases in the order no ligand < 18-crown-6 < [2.2.2]-cryptand. This difference was attributed to the fact that the enolate anion in a crown-ether complex is still capable of interacting with the cation, which stabilizes conformation [96]. For the cryptate, however, cation-anion interactions are less likely and electrostatic repulsion will force the anion to adopt conformation [99], which is the same as that of the free anion in DMSO. This explanation was substantiated by the fact that the anion was found to have structure [96] in the solid state of the potassium acetoacetate complex of 18-crown-6 (Cambillau et al., 1978). Using 23Na NMR, Cornelis et al. (1978) have recently concluded that the active nucleophilic species is the ion pair formed between 18-crown-6 and sodium ethyl acetoacetate, in which Na+ is co-ordinated to both the anion and the ligand. 

Probably the most significant examples of carbon nucleophiles are enolate anions. These can participate in a wide variety of important reactions, and simple nucleophilic substitution reactions are included amongst these. However, we shall consider these reactions at a later stage, when the nature and formation of enolate anions is discussed (see Chapter 10). 

In Section 10.6 we shall meet the Mannich reaction, where an imine or iminium ion acts as an electrophile for nucleophiles of the enolate anion type. 

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