Boron enolates stability

The kinetically controlled nucleophilic addition of preformed lithium enolates onto carbonyl compounds is reversible with a low activation barrier, and the thermal conditions are likely to have a major impact on the stereoisomeric ratio of the final aldols through the retroaldolization and the thermodynamic equilibration of lithium enolates76. The tendency of aldolates to undergo retroaldolization increases with the stability of enolates, and when going from lithium to potassium. On the other hand, boron enolates usually undergo completely irreversible aldol reaction511,512. 

Coupling of silyl enol ethers or boron enolates with Co2(CO)6-stabilized carbocations, generated via Lewis acid treatment of the appropriate propargyl ethers or aldehydes (aldol reaction), via the Nicholas reaction has been used to obtain large, highly strained, ring ketones. 

Acetylenic cobalt complexes greatly facilitate the heterolytic cleavage of adjacent alcohols or ethers. On treatment with Lewis acids, these complexes afford cobalt stabilized carbenium ions, which can be captured by nucleophiles such as enolates. Jacobi and Zheng have employed chiral boron enolates of Evans s oxa-zolidinone 6.91 (R = i-Pr). After removal of the chiral auxiliary, they obtained anti adds 11.43 with a high selectivity [1677] (Figure 11.9). The reaction can be extended to the boron enolates of related oxazolidinones and to a-branched propargyl derivatives. This reaction has been applied to the synthesis of P-aminoacids after Curtius rearrangement and oxidation of the triple bond [1677]. 

Of the various imines known to condense with active methylene compounds, a-arylimines have been the most widely used, especially in earlier work, because of their stability, ease of preparation and the absence of enolizable protons. Aliphatic imines containing enolizable protons have broader synthetic applications but their use is more restricted because they are prone to deprotonation and self aldol type condensations. As will be discussed, new methods utilizing Lewis acids and the less basic boron enolates have been devised to overcome the problem of deprotonation. Other innovations that have extended the scope of imine condensations include in situ methods for the preparation of elusive formaldehyde imines (CH2=NR2> and the utilization of A/-heterosubstituted imines (N = Si, O and S) for the synthesis of primary Mannich bases and A(-unsubstituted 3-lactams, available via hydrolysis or reduction of the N—X bond. 

Treatment of a-iodo ketone and aldehyde with an equimolar amount of Et3B yielded the Reformatsky type adduct in the absence of PhaSnH (Scheme 21), unlike ot-bromo ketone as shown in Scheme 15 [22], Ethyl radical abstracts iodine to pro-duee carbonylmethyl radical, which would be trapped by EtsB to give the corresponding boron enolate and regenerate an ethyl radical. The boron enolate reacts with aldehyde to afford the adduct. The three-component coupling reaction of tert-butyl iodide, methyl vinyl ketone and benzaldehyde proceeded to give the corresponding adduct 38, with contamination by the ethyl radical addition product 39. The order of stability of carbon-centered radical is carbonylmethyl radical > Bu > Pr > Ef > Me . 

Aldol reactions using the lithium enolate of the acylated auxiliary shown here fail to give good selectivities, so instead we use the boron enolate. The combination of triethylamine and the boron triflate form the stable boron enolate, whch has to be cis because the size of the auxiliary prevents the trans enolate forming. Boron has an empty p orbital, and donation into this orbital from the oxygen of the carbonyl group stabilizes the enolate. 

If the pKa of the corresponding acid R1 - H from the stabilized carbanion is smaller than 35, the migration of R1 fails in (dichloromethyl)borate complexes. Failure to convert pinanediol [(phenylthio)methyl]boronate to an a-chloro boronic ester has been reported15. Reaction of (dichloromethyl)lithium with an acetylenic boronic ester resulted in loss of the acetylenic group to form the (dichloromethyl)boronate, and various attempts to react (dichloromethyl)boronic esters with lithium enolates have failed17. Dissociation of the carbanion is suspected as the cause, but in most cases the products have not been rigorously identified. 

Thermodynamic control. Note that it is also possible for the aldolate adduct to revert to aldehyde and enolate, and equilibration to the thermodynamic product may afford a different diastereomer (the anti aldolate is often the more stable). The tendency for aldolates to undergo the retro aldol addition increases with the acidity of the enolate amides < esters < ketones (the more stable enolates are more likely to fragment), and with the steric bulk of the substituents (bulky substituents tend to destabilize the aldolate and promote fragmentation). On the other hand, a highly chelating metal stabilizes the aldolate and retards fragmentation. The slowest equilibration is with boron aldolates, and increases in the series lithium < sodium < potassium, and (with alkali metal enolates) also increases in the presence of crown ethers. ... 

They are conveniently isolated and stored as ethanolamine esters, which owe their air-stability to their cyclic boroxazolidine structure (3.24) in which the four co-ordinate boron is protected from attack by nucleophiles such as water or molecular oxygen. 8-Hydroxyquinoline, j8-ketoesters and jS-keto enols form similar derivatives, and their acetylacetonates (3.25) result from the smooth cleavage of one alkyl group from trialkylboranes R3B ... 

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