Enolates synthons representing

Recently, the improved chiral ethyl ketone (5)-141, derived in three steps from (5)-mandelic acid, has been evaluated in the aldol process (115). Representative condensations of the derived (Z)-boron enolates (5)-142 with aldehydes are summarized in Table 34b, It is evident from the data that the nature of the boron ligand L plays a significant role in enolate diastereoface selection in this system. It is also noteworthy that the sense of asymmetric induction noted for the boron enolate (5)-142 is opposite to that observed for the lithium enolate (5)-139a and (5>139b derived from (S)-atrolactic acid (3) and the related lithium enolate 139. A detailed interpretation of these observations in terms of transition state steric effects (cf. Scheme 20) and chelation phenomena appears to be premature at this time. Further applications of (S )- 41 and (/ )-141 as chiral propionate enolate synthons for the aldol process have appeared in a 6-deoxyerythronolide B synthesis recently disclosed by Masamune (115b). 

The keto-acid 24 is best disconnected at the branchpoint where the chain joins the ring giving the available cyclohexenone 25 and the enolate synthon 26 best represented by malonate 27. 

An important family of disconnections follows. The alkylations represented by 4c(i), 4c(ii) and 4c(iii) belong to extended enolate chemistry and you will learn to call the synthons 9,10 and 11 the a, y and a extended enolates. Synthons 9 and 11 react in the normal d2 position but 10 has d4 reactivity. There are obvious questions of regioselectivity in this family. This chemistry will not be discussed further in this chapter as it is the subject of chapter 11. 

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

Thus, [ri2-alkene-Fp]+ complexes represent useful cationic synthons for the vinyla-tion of enolates [31]. 

The disconnection is of the newly formed C-C bond 14a and is not the same as 8a. The synthons are represented by the enolate anion and a carbon electrophile. We saw alkyl halides in this role in chapter 13 but in the next 10 chapters we shall be mostly interested in combining enol(ate)s with carbonyl compounds. 

Another odd-numbered relationship means we can still use synthons of natural polarity. The 1,5-diketone 1 disconnects to a d2 synthon, an enolate, and an a3 synthon 2, that you should realise (chapter 6) is represented by the reagent 3. The conjugation in the enone makes the terminal carbon atom electrophilic. 

The problem of unnatural polarity also arises in making C-C disconnections for the synthesis of 1,4-difunctionalised compounds. If we start with 1,4-diketones 1, disconnection in the middle of the molecule gives a synthon with natural polarity 2, represented in real life by an enolate 4, and one of unnatural polarity, the a2 synthon 3 represented by some reagent of the kind we met in chapter 6 such as an a-haloketone 5. 

We mentioned the dimer of ketene 6 itself at the start of this chapter it is a cyclic enol ether and a good acylating agent. Nucleophiles attack the carbonyl group 39 expelling the enolate 40 of the acetoacetyl derivative 41. The disconnection is shown on 41 and the ketene dimer represents synthon 42. 

You will perhaps realise from these particular examples that the d2 synthon will be represented in real life by an enolate or its equivalent and the a3 synthon by an a, 3-unsaturated carbonyl compound, both displaying the natural polarity of these fragments. It is generally true that even numbered donor synthons (d2, d4, etc.) and odd numbered acceptor synthons (a1, a3, etc.) have natural polarity while the odd numbered donor synthons (d1, d3, etc.) and the even numbered acceptor synthons (a2, a4, etc.) have unnatural polarity or umpolung. This makes the numbering of such synthons a useful quick check on the type of reagent likely to be needed. 

Enolisation 1 involves the removal of the a-proton from a carbonyl compound to form an enolate ion 2. Homoenolisation involves the removal of a (i-proton 3 to form the homoenolate ion 4 or 5. Both the enolate and the homoenolate can be represented as carbanions, but whereas the enolate version 2b is merely a different way of representing a single delocalised structure, the homoenolate 5 is a different compound from the cyclopropane 4. No literal examples of homoenolates 5 are known so they have the status of synthons which may be represented in real life by reagents derived from cyclopropanols 4 among many other possibilities.1... 

The synthetic value of homoenolates, in exact analogy to that of enolates, stems from their amphoteric nature (equations 1 and 2). In addition, homoenolates represent archetypal synthons in the concept of umpolung , acting as inverse polarity nucleophilic synthons of Michael acceptors. 

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