Acetate enolate equivalents, chiral

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... 

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. 

Moreover, this two-step equivalent of an aldol condensation can proceed with high enantioselectivity in the presence of a chiral auxiliary. Thus reaction of the enolate of chiral silyl ketene acetal (5) with isobutyryl chloride gives 6 in 89% yield and 94% ee after reduction of the intermediate. 

Reagent 88 also ranks among the most highly enantioselective chiral acetate aldol enolate equivalents (a) Braun, M. Angew. Chem., Int. Ed. Engl. 1987, 26, 24, and literature cited therein, (b) Masamune, S. Sato, T. Kim, B. M. Wollmann, T. A. J. Am. Chem. Soc. 1986,... 

Since then, efficient catalytic asymmetric methods have been developed for the addition of silyl enol ethers or silyl ketene acetals to imines with chiral metal catalysts [29-34], Recently, direct catalytic asymmetric Mannich reactions which do not require preformation of enolate equivalents have appeared. 

S. G. Davies, H. M. Kellie, and R. Polywka, Opening of carbohydrate 5,6-epoxides with chiral acetate and propionate enolate equivalents attached to the iron chiral auxiliary [(C5H5)Fe(CO)P(Ph)3], Tetrahedron Asymmetry, 5 (1994) 2563-2570. 

Treatment of chiral, nonracemic vinyl sulfoxides (214) with O-silylated ketene acetal (215) in the presence of a catalytic amount of zinc chloride resulted in an enantioselective additive Pummerer-type reaction, affording the corresponding enantiomerically enriched methyl-4-siloxy-4-sulfenylbuyrate (216) (Scheme 55).122 This is the overall addition of the enolate equivalent to the vinyl sulfoxide. 

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. ... 

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. ... 

Braun M, Devant R. R)- and (5)-2-acetoxy-l,l,2-triphenyle-thanol—effective synthetic equivalents of a chiral acetate enolate. Tetrahedron Lett. 1984 25 5031-5034. 

We decided to investigate the E wis aldol reaction (54,55) of the chiral a-hydroxy acetic anion equivalent 47 with the A -Cbz imine of trifluoropyruvate 33. Screening of several enolates and reaction conditions revealed that titanium enolate of the oxazolidinone 47, prepared with 1 equiv. ofTiCU and l.l equiv. of/-Pr2NEt, reacts with excellent stereocontrol affording the "Evans" syn diastereomer 48, in 88% isolated yield, having the correct stereochemistry to be used as intermediate for the synthesis of the targeted 2-Tfm-sphingolipids. 

The chiral enolate-imine addition methodology was examined in detail (Thiruvengadam et al., 1999). Enolate formation proceeds to completion within an hour at temperatures from — 30 to 0°C with either 1 equiv. TiCl4 or TiClaO-iPr (preformed or prepared in the presence of substrate by addition of TiCl4 and followed by a third of an equivalent Ti(0-iPr)4 and two equivalents of a tertiary amine base). Unlike the aldol process with the same titanium enolate, the nature of the tertiary amine base had no effect on the diaster-eoselectivity. The diastereoselectivity is maximized by careful control of the internal temperature to below — 20°C during the imine addition (2 equiv.) as well as during the acetic acid quench. The purity of the crude 2-amino carboxamide derivatives (17a or... 

The conversion of an a, -unsaturated aldehyde or ketone into an allylic acetal or ketal, followed by SN2 -type attack of a nucleophile, leads, after hydrolysis of an initially formed enol ether, to a fi-sub-stituted carbonyl compound. The overall sequence (Scheme 23) is equivalent to a direct conjugate addition, but has the advantage that it allows the temporary introduction of a chiral auxiliary group if a chiral (C2-symmetric) diol is used in the acetalization step, die subsequent nucleophilic addition leads to a mix-... 

Asymmetric alkylation of dimclhoxyphosphoryl-AH 1 -(.S,)- -mclhylbenz i]acet-amide enolates has been reported 65 The synthesis of both stereoisomers from the same source of chirality has been achieved by changing the equivalents of LDA. 

Enol acetates and corresponding derivatives constitute another class of unsaturated compounds that can advantageously be hydrogenated with high enantiomeric excess. This reaction is related to the enantioselective reduction of ketones. Acylated enol carboxy-lates (as an equivalent of a-keto carboxylic acid) can likewise be successfully reduced with rhodium(I) catalysts based on (5,5)-ethyl-DuPHOS (eq 8). Subsequent deprotection of the hydroxyl group or reduction of the carboxylic acid derivatives so obtained deliver chiral a-hydroxy carboxylates and 1,2-diols, respectively. 

An important development is the use of D-glucose-derived alkoxy ligands on titanium in cyciopentadi-enyldi(alkoxy)titanium enolates, which undergo efficient enantioselective aldol reactions with aldehydes. The chiral titanium reagent (30), prepared from reaction of cyclopentadienyltitanium trichloride with two equivalents of (l,2 5,6)-di-0-isopropylidene-a-D-glucofuranose, can be used to transmetal late the lithium enolate of t-butyl acetate in ether solution (equation 10). The titanium enolate generated is then... 

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