Dialkylboron triflates

The deprotonation of the (1-oxopropyl) group of these compounds is achieved either by treatment with lithium dialkylamides or by the use of dialkylboron triflates in the presence of trialkylamines. In each case, exclusive generation of the corresponding (Z)-cnoiate results. 

A further step towards improved selectivity in aldol condensations is found in the work of David A. Evans. The work of Evans [3a] [14] is based in some early observations from Meyers laboratory [15] and the fact that boron enolates may be readily prepared under mild conditions from ketones and dialkylboron triflates [16]. Detailed investigations with Al-propionylpyrrolidine (31) indicate that the enolisation process (LDA, THE) affords the enolate 32 with at least 97% (Z>diastereoselection (Scheme 9.8). Finally, the observation that the inclusion of potential chelating centres enhance aldol diastereoselection led Evans to study the boron enolates 34 of A(-acyl-2-oxazolidones (33), which allow not only great diastereoselectivity (favouring the 5yn-isomer) in aldol condensations, but offer a possible solution to the problem of enantioselective total syntheses (with selectivities greater than 98%) of complex organic molecules (see below, 9.3.2), by using a recyclisable chiral auxiliary. 

Vinyloxyboranes (boron enolates) are obtained in quantitative yield by reaction of silyl enol ethers with dialkylboron triflates in CH2C12 at —22 . The products can be used for stereoselective aldol condensations.3 Example ... 

Stereoselective aldot condensations. Mukaiyama et al. have reported that ketones are converted into vinyloxyboranes by reaction with dialkylboron triflates and a tertiary amine and that these enolates undergo regioselective aldol reactions with aldehydes (equation I). Mukaiyama used di-n-butylboryl triflate in combination... 

An effective control of the simple diastereoselectivity in boron-mediated aldol reactions of various propionate esters (162) was achieved by Abiko and coworkers (equation 45) °. They could show that under usual enolization conditions (dialkylboron triflate and amine) enol borinates are formed, which allowed the selective synthesis of 5yw-configured aldol products (Table 11). The enolization at low temperature (—78 °C) generated a (Z)-enolate selectively, which afforded mainly the syn diastereomer 164 after reaction with isobu-tyraldehyde (163), following a Zimmerman-Traxler transition-state. The anti diastereomer 164 instead was obtained only in small amounts (5-20%). 

Although stereoselective formation of enolates from acyclic ketones with bases such as LDA is rather difficult, stereodefined boron enolates are more readily accessible. In the Mukaiyama method, an ethyl ketone is treated with a dialkylboron triflate and a tertiary amine, usually i-Pr2NEt. The resultant Z-(0) boron enolates (also known as enol borinates) are believed to be formed under kinetic control by deprotonation of the Lewis acid-complexed substrate. Brown and co-workers have shown that E- 0) boron enolates may be prepared by treatment of ethyl ketones with dicyclohexylboron chloride in the presence of Et3N. ... 

When treated with dialkylboron triflates, thioesters preferentially form (E)-(O) boron enolates, which react with aldehydes to afford good yields of the 2,3-anti aldol products. 

Catalytic hydrogenation of 1 in the presence of rhodium on aluminum oxide proceeds smoothly to afford (5)-hexahydromandelic acid (3) [2]. Subsequent treatment of 3 with ethyllithium provides in 75% yield the ketone 4, which is 0-silylated to afford 5. Generated in situ with the appropriate dialkylboron triflate and 5, the boron enolates 6a—c react with a variety of aldehydes to provide exclusively a mixture of syn-d o products 7 and 8 in 70-80% yields, often with excellent stereoselectivities. 

Excellent results have been obtained by using boron enolates (alkenyloxyboranes or enol borinates), in what is commonly known as a boron-mediated aldol reaction. The boron enolates are prepared easily from the corresponding ketone and a dialkylboron trifluoromethanesulfonate (dialkylboron triflate, R2BOTf) or chloride (R2BCI) and a tertiary amine base. Boron enolates react readily with aldehydes to give, after oxidative work-up of the resulting borinate species, high yields of the desired aldol product (1.58). 

Mukaiyama pioneered the cross aldol reaction involving dialkylboron triflates (28) (Figure 5). Later developments by Evans, Masamune, and others brought this area to new heights (29). However, research in this direction was not complete until we developed a procedure to prepare ann -aldols using fi-chlorodicyclohexylborane (30). This reagent has been utilized in several syntheses, especially in situations where the substrate controls the chirality. 

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