6-hydroxyesters from

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of / -hydroxyketones from /J-sulfinylhydrazones 166211-214, of /3, /l -dihydroxyketones from 3-(p-tolylsulfinyl-methyl)-A2-methylisoxalinones 167215, of /1-hydroxyacids from 2-(p-tolylsulfinylmethyl)oxazolines 168216 and of /J-hydroxyesters from ethyl-p-tolylsulfinyl-W-methoxyacetamide 169217. 

B-hydroxyesters from, 53, 69 a-deuterio-, 53, 82 preparation using 1,3-dithiane,... 

Chow KYK, Bode JW (2004) Catalytic generation of activated carboxylates direct, stereoselective synthesis of fi-hydroxyesters from. J Am Chem Soc 126 8126-8127... 

Synthesis of p-hydroxyesters from carbonyl derivatives and a-halo esters via a zinc reagent (Reformatsky). Synthesis of p-ketoesters from nitriles and a-halo esters via a zinc reagent (Blaise) (see 1st edition). 

Lithium borohydride supported on zeolite A or X will bring about the selective reduction of aldehydes without reducing any ketones that may be present [102]. Lithium aluminium hydride in the presence of silica gel reduces ketones rapidly and in high yield without affecting cyano or nitro groups (e.g. equation 4.19) [103]. The same reagent also selectively reduces carboxylic esters when other reducible groups are present and facilitates the formation of hydroxyesters from ketoesters [104]. 

Table 6.28 Synthesis of e yf/iro-P-hydroxyesters from boron azaenolate [ 13]...

The protection of carboxylic acids as their phenacyl esters has been described regeneration is effected with great facility at room temperature by zinc in glacial or dilute aqueous acetic acid. Of notable applicability is the formation of y-hydroxyesters from y-lactones, an otherwise indirect transformation an example is the obtention of the ester (13) from the sodium salt of santonin (12). This protection can be extended to phenols. 

L. Vuitel, A. Jacot-GuiUannod, Preparation of 3-hydroxyesters from carbonyl compounds and ketene in the presence of titanium alkoxides. Synthesis 11, 1972 608. 

Lezl980 Leznoff, C.C. and Yedidia, V, The Solid Phase Synffiesis of Tertiary Hydroxyesters from Symmetrical Diacid Chlorides using Organomanganese Reagents, Can. J. Chem., 58 (1980) 287-290. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

For this reaction, CALB catalyzes the amidation between a racemic P-hydroxyester and racemic amines, leading to the corresponding amide with very high enantiomeric and diastereomeric excesses. Besides, the remaining ester and amine are recovered from the reaction media, also showing good enantiomeric excesses. By this method, three enantioenriched interesting compounds are obtained from an easy one-step reaction. 

Baker s yeast has been widely used for the reduction of ketones. The substrate specificity and enantioselectivity of the carbonyl reductase from baker s yeast, which is known to catalyze the reduction of P-keto ester to L-hydroxyester (L2-enzyme) [15], was investigated, and the enzyme was found to reduce chloro-, acetoxy ketones with high enantioselectivity (Figure 8.32) [24aj. 

A similar sequence starting with the acylation product (76) from metachlorophenylacetonitrile gives the halogenated tricyclic ketone 83. Condensation of that intermediate with ethyl bromoacetate in the presence of zinc (Reformatsky reaction) gives the hydroxyester 84. This product is then in turn dehydrated under acid conditions (85), saponified to the corresponding acid (86), and converted to the dimethyl-amide (87) by way of the acid chloride. The amide function is then reduced to the amine (88) with lithium aluminum hydride catalytic hydrogenation of the exocyclic double bond completes the synthesis of closiramine (89). This compound also exhibits antihistaminic activity. 

We felt the Reformatsky reaction was a worthwhile target because it is the most generally applicable method for converting aldehydes and ketones to ff-hydroxyesters(25). The improvements in yield and reaction time exceeded our expectations. Essentially quantitative conversion to the 0-hydroxyester was effected in a matter of a few minutes(26). The absence of other products, such as a, 0-unsaturated esters, resulting from dehydration, and dimers of the bromo ester and the carbonyl are probably the result of running... 

Isolation of the diesters and hydroxyesters/alcohols fraction by anion exchange chromatography with an aminopropyl cartridge from a solution of 1 mg ml-1 of raw beeswax in CHCU/MeOH (2 1, v/v)... 

C-H insertion a to oxygen results in the formation of /3-hydroxyester derivatives that are generally prepared from aldol reactions (Figure 3). For the C-H insertion chemistry to be a viable surrogate of the aldol reaction, the reaction would need to be highly diastereoselective and enantioselective. 

Furthermore, 2,2-difluoro-3-hydroxyesters are readily obtained from ClCF2COOMe and carbonyl compounds by electrolysis in a one-compartment cell using a sacrificial zinc anode and a nickel-complex catalyst [26], The catalytic cycle is shown in Scheme 3.11 and nickel zinc exchange is a key step. 

The much lower thermodynamic stability of hemiorthoesters compared to hemiacetals is illustrated by comparing the equilibrium constant for the formation of [121] from the corresponding hydroxyester, 5 x 10-7 to 1 x 10" 6 (Table 17) with that for the formation of hemiacetal [123] from the corresponding hydroxyaldehyde [122] which is 8.1 in 75 25 dioxan-water... 

Recently, Zhu and coworkers have investigated the reaction of the zinc reagent from ethyl 3-bromodifluoromethyl-3-benzyloxyacrylate. The exclusive zinc reagent formed in DMF was the -carbon metallated product (equation 88)82. These workers utilized this reaction to prepare -dilluorovinyl substituted / -hydroxyesters in high yields and high regioselectivity via the reactions of aldehydes mediated by zinc (equation 89)82. 

C of the acetal and the Lewis acid. Enantiomerically pure cyclic acetals 49 deriving from chiral diols open a route to adducts 50, which can be successively elaborated to chiral /9-hydroxyesters upon oxidation of the alcoholic group followed by alkaline elimination (equation 33). 

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