Acetate enolates chiral

Scheme 27 Addition of nitronates, enolates and silyl ketene acetals to chiral a-amino imines and iminium ions...

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

The importance of the (Z)-enolate substitution has been noted elsewhere in this chapter (see Table 32). A practical solution to the generation of a useful chiral acetate enolate synthon has been to employ a substituted enolate where the ligand Rj may be removed after the aldol condensation. Enolate 149b (Rj = SMe) serves this purpose adequately (eq. [102]). The resultant alddl adducts 151b... 

It should also be noted that there is a strong conformational bias for only one of the product chelate conformers. For example, erythro chelate D should be strongly disfavored by both 1,3-diaxial Rj L and CH3 Xq steric control elements. Consequently, it is assumed that the transition states leading to either adduct will reflect this conformational bias. Further support for these projections stems from the observations that the chiral acetate enolates derived from 149a exhibit only poor diastereoface selection. In these cases the developing Rj CH3 interaction leading to diastereomer A is absent. Similar transition state allylic strain considerations also appear to be important with the zirconium enolates, which are discussed below. 

Further support for this explanation is the fact that the chiral acetate enolates derived from A -acetyl-2-oxazolidone (46). in which the developing Rj <-> CH3 interaction leading to diastereomer A is absent, exhibit only poor diastereofacial selection. 

An additional indication of the mildness of the cyclization is provided by the synthesis of the chiral tetrahydroisoquinoline-3-carboxylic acid (294) (72HCA15) in the presence of hydrogen and palladium-on-charcoal the jV-methyl derivative was obtained. Acetaldehyde gave a mixture of diastereoisomers in which the cis isomer (295) predominated (95 5). Unstable aldehydes can sometimes be generated in situ, as when the phenylglycidate (296) replaces the much less stable phenylacetaldehyde (66T(S8)129) acetals, enol ethers and chloromethyl methyl ethers have also been used. The mild conditions also allow the isolation of 4-hydroxytetrahydroisoquinolines (297) (75H(3)311). A review is available listing syntheses of 4-oxytetrahydroisoquinolines (73AHC(15)99). 

In a one-pot reaction, a series of ketones were converted to chiral acetates with the help of an achiral ruthenium complex and CALB at 1 atm of hydrogen gas in ethyl acetate. Molecular hydrogen was equally effective in the transformation of enol acetates to chiral acetates in the same catalyst system without addition of additional acyl donors (Jung, 2000b). 

J. Park, Practical ruthenium/lipase-catalyzed asymmetric transformations of ketones and enol acetates to chiral acetates,... 

Using a chiral 4-dimethylaminopyridine-ferrocenyl catalyst, acyclic silyl ketene acetals react with anhydrides to furnish 1,3-dicarbonyl compounds containing allcarbon quaternary stereocentres in good yield and ee.144 Evidence for dual activation (anhydride -> acylpyridinium, and acetal -> enolate) is presented. 

The reagent (2) is probably the most versatile chirally modified acetate enolate. Good results have also been obtained with the Mg enolate of 2-acetoxy-l,l,2-triphenylethanol and with boron enolates derived from 2,4-dialkylborolanes Chiral Fe-acetyl complexes, which can be considered as acetate equivalents, give impressive stereocontrol upon enolization and aldol reaction. ... 

Nucleophilic addition of ester enolates to enantiopure nitrones, followed by cyclization of the resulting hydro-xylamine, is a general approach to isoxazolidin-5-ones and can be applied to the stereoselective synthesis of these heterocycles <2005CRC775>. In some cases, the cyclization occurs spontaneously under the reaction conditions. For example, the addition of the sodium enolate of methyl acetate to chiral nitrone 551 gave directly the isoxazolidin-5-ones 552 in quantitative yield and high ty -diastereoselectivity (Equation 91) <1998CC493>. 

Stereoselective aldol reactions of menthyl acetate enolates, and allylations with benzaldehyde mediated by mono-Cp monochloro bis-alkoxo chiral titanium complexes have been reported.972... 

The synthesis of the racemic dihydropyrones has previously been described.24,30,31 The chiral synthesis of the dihydropyrones is shown in Scheme 1 as reported by Christopher Gajda.16,17 The ketone 131 was reacted with the appropriate acetate enolate to afford 132,134, or 136. The resulting ester was converted into the acid 133 by either hydrolyzing the alkyl ester or hydrogenating the benzyl ester. The resulting racemic acid was resolved by classical resolution with a variety of chiral amines to afford resolved 135. An alternative route to chiral acid 138 was achieved by resolution of the intermediate ester using chiral columns and... 

Diastereoselective Aldol Additions of Chiral Silyl Ketene Acetals and Chiral Silyl Enol Ethers... 

The ferrocenyldiphosphine ligand 99 constitutes a catalytic system with (cod)2RhBp4 for synthesizing a-alkylsuccinic acid derivatives from the alkylidene compounds. Secondary acetates in chiral form are accessible from hydrogenation of enol acetates using the catalytic system of (cod)2RhBF4-100. ... 

Mandelic acid-derived chiral (a-substituted) acetate enolate addition to aldehydes leading to chiral j5-hydroxycarboxylic acids illustrates the versatility of the readily available ester 63. The addition of phenylmagnesium bromide to methyl (i )-mandelate (63) gives the (i )-diol 152, which is acetylated to (i )-2-acetoxy-l,l,2-triphenylethanol (153) [(/ )-HYTRA]. Deprotonation with LDA at — 78 °C provides an enolate that is then transmetallated with magnesium bromide and further cooled to —115 °C before reaction with an aldehyde to produce 154 as the major diastereomer with a yield of 84-95%. Heating 154 in aqueous methanol containing potassium hydroxide provides the optically active j5-hydroxyacid 156 (Scheme 36) [41- 4]. 

A relatively concise synthesis of a compactin lactone (99) derivative makes use of 590 as the source of chirality (Scheme 93) [142]. Addition of ethyl acetate enolate to 590 produces a 1 1 mixture of aldols 633 in 58% yield. After silylation of the hydroxyl group, cleavage of the acetonide furnishes lactone 635 as a crystalline solid. Tosylation of the primary alcohol and separation of the isomers furnishes 636 (47% yield) and 637 (44% yield). The desired isomer 636 is a suitably protected and functionalized version of compactin lactone . 

The goal of introducing a nucleophile to an enone 1,4 enantioselectively has been reported by the use of both chiral enones and chiral nucleophiles. The former strategy is exemplified by a synthesis of natural (-)-methyl jasmonate by the addition of an acetate enolate equivalent to a chiral... 

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