Enolates continued reaction with aldehydes

The same catalyst is also effective in three-component reactions between aldehydes, amines, and silylated nucleophiles, leading to amino ketone, amino ester, and amino nitrile derivatives, respectively (Eq. 30) [114]. It is reported that 103 can be recovered and that continuous use is possible without any loss of activity. More interestingly, in competitive reaction of aldehyde, aldimine and silyl enolate, the less reactive aldimine reacted exclusively with silyl enolate in the presence of 103. This unique selectivity was explained by the polymer effect [115]. 

The aldol reactions of aldehydes with silyl enol ethers were also found to proceed smoothly in water-ethanol-toluene (1 7 4) [19]. Some reactions proceeded much faster in this solvent system than in THF-water. Furthermore, the new solvent system enabled continuous use of the catalyst by a very simple procedure. Although the water-ethanol-toluene system was one phase, it easily became two phases by adding toluene after the reaction was completed. The product was isolated from the organic layer by a usual work-up. On the other hand, the catalyst remained in the aqueous layer, which was used directly in the next reaction without removing water. It is noteworthy that the yields of the 2nd, 3rd, and 4th runs were comparable to that of the 1st run (Eq. (14.2)). 

In the nineteen-eighties many researchers developed a variety of Lewis acid catalysts of the Mukaiyama aldol reaction. In particular, TrClO4 [23] and TMSOTf [24] effectively promote reaction of silyl enolates with aldehydes or acetals. These studies suggested that introduction of a soft Lewis base such as the CIO4 or OTf anion into the Lewis acidic center should lead to effective catalysts. Based on this concept, further studies have been continued to develop novel Lewis acid catalysts with higher catalytic activity or higher chemo- and stereoselectivity. 

The aldol reactions of silyl enol ethers with aldehydes were also found to proceed smoothly in water-ethanol-toluene [20]. Some reactions proceeded much faster in this solvent system than in THF-water. Furthermore, the new solvent system realized continuous use of the catalyst by a very simple procedure. 

Kobayashi and coworkers reported addition of enol silanes (72) to aldehydes (71) catalyzed by Cu(OTf)2/(52) (Scheme 17.14) [19]. Moderate to good enantioselectivities could be obtained with low syn/antiselectivity. The reduced enantioselectivity relative to bidentate acceptors employed may be attributed to single-point coordination to the Lewis acid. This point is noteworthy, as acceptors restricted to single-point coordination continue to be challenging substrates in copper-catalyzed aldol reactions. 

Boron.—Whereas in 1981 a considerable amount of work relating to the use of boron enolates in enantio- and stereo-selective aldol condensations was reported, the last 12 months have seen a shift of emphasis and the publication of a number of papers continuing and extending the well known ability of allyl-boranes to function in these reactions. A good example of this is the paper by Midland describing the condensation of enantiomerically enriched allylboranes (93) with aldehydes R CHO to give the homoallylic alcohols (94). Enantiomeric excesses of up to 85% (R = isopinocampheyl) are observed in the reaction, and threo erythro ratios are in the range 96 4 to 99 1. 

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 mixed Tishchenko reaction involves the reaction of the aldol prodnct 113 from one aldehyde with another aldehyde having no a-hydrogens to yield an ester The products were proposed to be formed through an aldol step (equation 33), followed by addition of another aldehyde (equation 34) and an intramolecular hydride transfer (equation 35). However, several aspects of this mechanism need to be clarified. As part of the continuing mechanistic studies carried out by Streitwieser and coworkers on reactions of alkali enolates ", it was found that the aldol-Tishchenko reaction between certain lithium eno-lates and benzaldehyde proceeded cleanly in thf at room temperature". Reaction of the lithium enolate of isobutyrophenone (Liibp) with 1 equiv of benzaldehyde in thf at — 65 °C affords a convenient route to the normal aldol product 113 (R = R" = Ph, R = Me). At room temperature, however, the only product observed after acid workup was the diol-monoester 116, apparently derived from the corresponding lithium ester alcoholate (115, R = R" = Ph, R = Me), which was quantitatively transformed into 116 after quenching. As found in other systems", only the anti diol-monoester diastereomer was formed. 

Now the aldehyde is added. If the reaction is to take place, the aldehyde must coordinate to the boron because boron enolates aren t reactive enough to attack aldehydes unless they are activated by coordination to a Lewis acid. However, the aldehyde can t simply coordinate to the boron atom of the enolate because then the boron will end up with five bonds, which is impossible for a first-row element. So, if the reaction is to continue, the boron has to let go of the auxiliary s carbonyl group and coordinate to the aldehyde instead. 

The bicyclo[2,2,l]heptane system also continues to find employment for the assessment of new synthetic procedures, or for testing the efficacy of new reagents. Isolated yields of 50—65 % of ap-unsaturated aldehydes have been obtained by reaction of alkyl tosylhydrazones with butyl-lithium, addition of DMF, and hydrolysis however, reaction of camphor tosylhydrazone (381 X = NNHTs) according to this procedure only gave 10 % of the aldehyde (382 X = CHO), presumably because of unfavourable steric effects. " Trimethylsilyl trifluoromethanesulphonate is a mild reagent for converting carbonyl compounds into trimethylsilyl enol ethers, for example the production of (382 X = OSiMcj) from camphor (381 X = Experimental details... 

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