Ketenes boron enolates

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Asymmetric Mannich reactions provide useful routes for the synthesis of optically active p-amino ketones or esters, which are versatile chiral building blocks for the preparation of many nitrogen-containing biologically important compounds [1-6]. While several diastereoselective Mannich reactions with chiral auxiliaries have been reported, very little is known about enantioselective versions. In 1991, Corey et al. reported the first example of the enantioselective synthesis of p-amino acid esters using chiral boron enolates [7]. Yamamoto et al. disclosed enantioselective reactions of imines with ketene silyl acetals using a Bronsted acid-assisted chiral Lewis acid [8]. In all cases, however, stoichiometric amounts of chiral sources were needed. Asymmetric Mannich reactions using small amounts of chiral sources were not reported before 1997. This chapter presents an overview of catalytic asymmetric Mannich reactions. 

As above (eq 1), a major drawback of this reagent is the lack of a readily available enantiomer. There are many alternative methods for the enantioselective propionate aldol reaction. The most versatile chirally modified propionate enolates or equivalents are N-propionyl-2-oxazolidinones, a-siloxy ketones, boron enolates with chiral ligands, as well as tin enolates. Especially rewarding are new chiral Lewis acids for the asymmetric Mukaiyama reaction of 0-silyl ketene acetals. Most of these reactions afford s yw-aldols good methods for the anri-isomers have only become available recently. ... 

Boron enolates can be formed with good stereoselectivity by the reaction of ketenes with dibutylthio-borinates (equations 29 and 30). ... 

Spiroketals have been obtained by RCM of cyclic ketals 18 without loss of stereochemical integrity at the spiro linkage <04TL5505> and a stereoselective solid-phase synthesis of 6,6-spiroketals has been reported in which aldol reactions of boron enolates are the key feature <04AG(E)3195>. Spiro orthoesters are accessible from thiophenyl ketene acetals and diols (Scheme 5) <04SL2013>. 

The answer is both For the Li enolate, the usual rule makes OLI of lower priority than OMe (because Li has a smaller atomic number than C), so it s E, while the silyl enol ether (or sllyl ketene acetal ) has OSI of higher priority than OMe (Si has a larger atomic number than C), so it s Z This is merely a nomenclature problem, but It would be irritating to have to reverse all our arguments for lithium and boron enolates (as opposed to, say, tin or silicon ones). So, for the sake of consistency, it is much better to avoid the use of E and Zwith enolates and Instead use cis and trans, which then always refer to the relationship between the substituent and the anionic oxygen (bearing the metal). 

In this context the Reformatsky type reaction of Gilman and Specter between a-bromoesters and imines, the lithium enolate-imine condensation and the use of silyl ketene acetals, boron enolates and tin(II) enolates have been successfully utilized in the synthesis of appropriately substituted P-lactams for carbapenem synthesis. 

Shibasaki [89a] has reported an asymmetric synthesis of (-h) PS-5 by using the boron enolate-imine condensation reaction. The most notable features of this approach were that the correct absolute stereochemistry at C3-C4 of the p-lactam ring was produced in a highly diastereoselective fashion and imines derived from aliphatic amines could be used in this reaction in a similar way to the silyl ketene acetal approach (Scheme 32). 

Many attempts have been made to add chiral acetates to aldehydes or prochiral ketones, to obtain non-racemic y -hydroxycarboxylic esters. Here again, several variants based on boron and titanium enolates and on Mu-kaiyama aldol additions of silyl ketene acetals have been developed, and will be described in Chapter 2 (titanium enolates). Chapter 3 (boron enolates) and in Part II (Mukaiyama reaction), for enolates of group 1 and 2 elements the following fruitful approaches were elaborated. 

Investigation of this mechanism reveals that the key intermediate of this reaction is vinyloxyborane (boron enolate) 7 generated from ketene 1 and alkylthioborane 6 (Eq. (2)) [2]. Thus, our original study on organo-thioboranes led us, unexpectedly, to discover the widely utilized aldol reactions via boron enolates [3]. 

Oppolzer s auxiliary opened, in addition, an access to a/iti-configured aldol adducts 272 (Scheme 4.62). For this purpose, silyl ketene N,0-acetal 271 was prepared from propionic sultam 92, obtained as a single diastereomer, according to the NMR spectra of the crude product, and isolated as a crystalline compound it was characterized as a cis-silicon enolate by a crystal structure analysis. For the subsequent Mukaiyama aldol addition, titanium tetrachloride was found to be the optimum Lewis acid to yield the awti-diastereomers 272 in excellent diastereoselectivity. Their formation under attack of the enolate to the Re-face of the aldehyde is consistent with an open transition state 275, wherein the Lewis acid-coordinated aldehyde is located on the face opposite to the sulfonyl group (Scheme 4.62) [136b]. An alternative approach to the a fi-aldol adducts was also elaborated, based upon cA-boron enolates 267 when they are reacted with aldehydes in the presence of titanium tetrachloride, an ti-selective aldol addition occurs leading to the products 272 rather than to sy -aldols 268 that result in the absence of the Lewis acid [136c]. 

The normal yn-selectivity of (Z)-boron and chlorotitanium enolates can be overridden by diverting the cyclic transition state of the aldolization processes to an open one . This can be accomplished either by using (Z)-0-silyl-iV,0-ketene acetals as starting materials " or by treating the boron enolate solution with an aldehyde pre-complexed with a second Lewis acid 406,112,113 latter case, enantiopure 2-oxazolidinone-... 

The enolates of other carbonyl compounds can be used in mixed aldol reactions. Extensive use has been made of the enolates of esters, thiol esters, amides, and imides, including several that serve as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, titanium, and tin derivatives have all been widely used. The silyl ethers of ester enolates, which are called silyl ketene acetals, show reactivity that is analogous to silyl enol ethers and are covalent equivalents of ester enolates. The silyl thioketene acetal derivatives of thiol esters are also useful. The reactions of these enolate equivalents are discussed in Section 2.1.4. 

Treatment of chromium (III) acetylacetonate with acetic anhydride and boron trifluoride etherate yielded a complex mixture of acetylated chelates but very little starting material. Fractional crystallization and chromatographic purification of this mixture afforded the triacetylated chromium chelate (XVI), which was also prepared from pure triacetylmethane by a nonaqueous chelation reaction (8, 11). The enolic triacetylmethane was prepared by treating acetylacetone with ketene. The sharp contrast between the chemical properties of the coordinated and uncoordinated ligand is illustrated by the fact that chromium acetylacetonate does not react with ketene. 

The lithium enolate generated using lithium diisopropylamide [4111-54-0], lithium 2,2,6,6-tetramethylpiperidide [58227-87-1], or lithium hexamethyldisilazide [4039-32-17 is a chemical reagent that reacts with other reactants to give a variety of products (37). In the quest for improved stereospecificity, enolates with different cations such as silicon, aluminum, boron, and zinc have also been used (38). In group transfer polymerization, ketene silyl acetals, eg, (CH3)2C=C [OSi(CH3)3] (OCH3) are employed as initiators (39). 

Catalysis with Ti(IV) Complexes and Boronates. Carreira has documented the addition of dienolsilane 105 to a broad range of aldehydes [28], Enolization of the commercially available acetone-ketene adduct 104 with LDA, followed by quenching with chlorotrimethyl silane, gave 105 in 78% yield as a clear colorless liquid that can be conveniently purified by distillation (Eq. 8B2.24). The addition reactions are conducted at 23°C utilizing 5 mol % 72 to give adducts with up to 94% ee (Eq. 8B2.25, Table 8B2.13). The aldol adducts 106 were isolated fully protected as the corresponding 0-silyl ethers with the P-keto ester masked in the form of a dioxinone. 

Most [3,3]-sigmatropic rearrangements take place thermally, and the Cope, oxy-Cope and Claisen rearrangements are among the most important rearrangements in this class. Important variants of the Claisen rearrangement include the Johnson modification via orthoesters, the Eschenmoser modification via ketene N,O-acetals, the Ireland modification via ketene silylacetals and the Corey modification via boron ester enolates [696], The aza-Claisen rearrangement has also seen... 

Silyl enol ethers and silyl ketene acetals add to aldehydes in the presence of a stoichiometric amount of a Lewis acid (generally titanium tetrachloride, boron trifluoride etherate, tin(IV) chloride) with low levels or a complete lack of simple stereoselection. The anti.syn ratios usually range from 25 75 to 80 20, depending on the particular aldehyde, Lewis acid, enol ether and on the double bond stereochem-... 

Enantiomerically pure boron-based Lewis acids have also been used successfully in catalytic aldol reactions. Corey s catalyst (7.10a) provides good enantioselectivity with ketone-derived silyl enol ethers, including compound (7.11). Other oxazaborolidine complexes (7.13) derived from a,a-disubstituted a-amino acids give particularly high enantioselectivity, especially with the disubstituted ketene... 

More recent advances in intermolecular [3+2] reductive cycloadditions have involved combinations of enals or enoates with alkynes (Scheme 3-34).l 2 l The initially developed cycloadditions of enals and alkynes likely proceeds by initial formation of a metallacyclic enolate derivative, followed by enolate protonation and addition of the vinyl nickel unit to the resulting carbonyl to produce the boron alkoxide of the observed cyclopentenol product (Scheme 3-35). The analogous transformation with enoates may also proceed by this mechanism, depicted below by the sequence of initial generation of metallacycle 20, followed by enolate protonation to form 21 en route to product generation. Alternatively, the collapse of the metallacycle 20 to a ketene intermediate 22 may occur in the enoate variant. The precise pathway followed likely depends on whether protic or aprotic media are used. 

Formation of p-hydroxy ketones via reaction of silyl enol ethers or ketene silyl acetals with aldehydes in presence of a Lewis acid, such as titanium tetrachloride, tin tetrachloride or boron trifluoride etherate ... 

---