Esters a-hydroxy

The reactions of 1,1,2,3,3,3-hexafluoropropyldiethylamine with secondary aliphatic p-hydroxy esters give reasonable to good yields of their corresponding fluondes, whereas aliphatic a-hydroxy esters yield mostly 2,3,3,3-tetrafluoropro-pionates [55] (equations 55 and 56)... 

A fluorinated keto ester reacts as an electrophile with hydrides, giving a hydroxy ester in a highly stereoselective reduction [30] (equation 25). 

FIGURE 14.25 Catalytic antibodies are designed to specifically bind the transition-state intermediate in a chemical reaction, (a) The intramolecnlar hydrolysis of a hydroxy ester to yield as products a S-lactone and the alcohol phenol. Note the cyclic transition state, (b)... 

A terpene yielding isofenchyl alcohol on hydration, which Wallach considers to be one of the fenchenes, was artificially prepared by converting nopinone into a hydroxy ester by means of bromoacetic ester and zinc-dust. The hydroxy ester is dehydrated by potassium bisulphate, and so yields an unsaturated ester, which on saponification yields an acid from which the terpene results by distillation. This fenchene has the following characters —... 

Some workers avoid delay. Pai)adium-on-carbon was used effectively for the reductive amination of ethyl 2-oxo-4-phenyl butanoate with L-alanyl-L-proline in a synthesis of the antihyperlensive, enalapril maleate. SchifTs base formation and reduction were carried out in a single step as Schiff bases of a-amino acids and esters are known to be susceptible to racemization. To a solution of 4,54 g ethyl 2-oxO 4-phenylbutanoate and 1.86 g L-alanyl-L-proline was added 16 g 4A molecular sieve and 1.0 g 10% Pd-on-C The mixture was hydrogenated for 15 hr at room temperature and 40 psig H2. Excess a-keto ester was required as reduction to the a-hydroxy ester was a serious side reaction. The yield was 77% with a diastereomeric ratio of 62 38 (SSS RSS)((55). 

Since 1,4-butanediol (BD) undergoes dehydration side reaction in the presence of acid resulting in THF formation, the hydroxy-ester interchange reaction is the preferred method for the preparation of PBT. The first stage of reaction is carried out at 150-200°C and consists of a hydroxy-ester interchange between DMT and excess butanediol with elimination of methanol. In the second stage, temperature is raised to 250°C and BD excess is eliminated under vacuum. Tetraisopropoxy-and tetrabutoxytitanium are efficient catalysts for bodi stages (Scheme 2.20). 

Likewise, C. parapsilosis was investigated for substrate tolerance in the deracemization reactions with aryl a-hydroxy esters (23) (Figure 5.16) [29]. A range of... 

Based on these preliminary findings, related couplings to pyruvates and iminoacetates were explored as a means of accessing a-hydroxy acids and a-amino acids, respectively. It was found that hydrogenation of 1,3-enynes in the presence of pyruvates using chirally modified cationic rhodium catalysts delivers optically enriched a-hydroxy esters [102]. However, chemical yields were found to improve upon aging of the solvent 1,2-dichloroethane (DCE), which led to the hypothesis that adventitious HC1 may promote re-... 

On treatment with acetic anhydride and pyridine, stephadiamine (16) was converted to W-acetylstephadiamine (22), which was hydrolyzed with potassium hydroxide followed by methylation, after acidification with dilute hydrochloric acid, with diazomethane to yield a hydroxy ester (23) in 93%... 

Effenberger and coworkers have utilized the tolerance of methyl ketones by the recombinant enzyme to develop an alternative synthesis of tetronic acids and their amino derivatives, as shown in Figure 5.18. Treatment of O-acyl cyanohydrins with lithium disilazide resulted in base-induced ring closure to amino tetronic acid derivatives. Alternatively, the cyanohydrins could be converted to a-hydroxy esters prior to acylation, and the same base-induced cyclization then led to tetronic acid derivatives [89]. 

Developments after these Ugi derivatives have taken a number of pathways. The MandyPhos family of ligands (32) have been used to reduce enamides to 01-amino acids as well as an enol acetate to produce an a-hydroxy ester [134—140]. The substituents R and R1 can be used for the fine-tuning of a specific substrate. Many of the family have R1 as a secondary amine, relating the family back to PPFA. For confusion, MandyPhos has also been called FerriPhos, while the derivative 32 (R = Rx = Et) is known as FerroPhos. 

Asymmetric reductions. The reagent can effect asymmetric reduction of alkyl aryl ketones and unhindered dialkyl ketones in high optical yield.1 It is the most useful reagent known to date for asymmetric reduction of even hindered a-keto esters to (S)-a-hydroxy esters in >90% ee.2 It is also effective for asymmetric reduction of phosphinyl imines of dialkyl ketones, RlR2C=NP(0)(C6H5)2 (50-84% ee).3... 

Magnesium iodide reacts with a,p-epoxy esters to form p-iodo-a-hydroxy esters selectively (200 1). The regioselectivity is attributed to favorable chelation of the iodohydrin. These products are reduced by Bu,SnH to overall yields with retention of the original configuration at the a-position. 

The considerable Lewis acidity of bis(oxazoline)-copper(II) complexes held promise for catalyzing the ene reaction, a process that usually requires strong Lewis acids. Indeed, these catalysts effect a highly selective ene reaction between a variety of alkene partners and glyoxylate esters to produce a-hydroxy esters in good yield, Eq. 210 (245). The ene reaction between cyclohexene and ethyl glyoxylate proceeds in excellent diastereoselectivity and enantioselectivity, Eq. 211. As a testament to the Lewis acidity of these complexes, it is noteworthy that... 

N. Borho and M. A. Suhm, Tailor made aggregates of a hydroxy esters in supersonic jets. Phys. Chem. Chem. Phys. 6, 2885 2890 (2004). 

Alkoxyallenes have also been subjected to oxidative reaction conditions [46, 62, 74, 132-134]. Ozonolysis of the already mentioned a-hydroxy-substituted methoxyal-lenes 230 provided a syn-anti mixture of a-hydroxy esters 231 (Scheme 8.58) [62]. 

Similarly, treatment of a-tosylamino-substituted allene 83 provided the expected a-amino ester 232 in good yield [74], The analogous reaction could also be performed with methoxyallene-aziridine adduct 46, which furnished enantiomerically pure /3-amino acid 233 [46], Although the ozonolysis approach seems to constitute a versatile and flexible method for the construction of a-amino and a-hydroxy esters, only a few examples have been reported so far. 

Asymmetric introduction of azide to the a-position of a carbonyl has been achieved by several methods. These include amine to azide conversion by diazo transfer,2 chiral enolate azidation,3 and displacement of optically active trifluoromethanesulfonates,4 p-nitrobenzenesulfonates,5 or halides.6 Alkyl 2-azidopropionates have been prepared in optically active form by diazo transfer,2 p-nitrobenzenesulfonate displacement,5 and the Mitsunobu displacement using zinc azide.7 The method presented here is the simplest of the displacement methods since alcohol activation and displacement steps occur in the same operation. In cases where the a-hydroxy esters are available, this would be the simplest method to introduce azide. 

After protection, the a-hydroxy esters can be reduced by DIBAL-H into O-protected a-hydroxyaldehydes that are very useful synthetic intermediates (e.g., leukotrienes,7-9 ionophore antibiotics,10 insect pheremones,11 etc.). The secondary hydroxyl group of the a-hydroxy esters may also be substituted with inversion of configuration after activation as triflates of nosylates (p-nitrobenzenesulfonates) to give a-alkyl esters12 ora-amino esters.13... 

Ethyl 2,3-epoxypropanoate is a very interesting chiron. It may be opened by various organometallic compounds such as dialkyl, diaryl, and divinyl lithium cuprates, dialkylmagnesium cuprates, trialkylalanes and aluminum acetylides.5 6 The epoxide ring is attacked regiospecifically at the p-position and produces a-hydroxy esters exclusively without racemization. The same result is observed with... 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

B. Borhan, A. D. Jones, F. Knot, D. F. Grant, M. J. Kurth, B. D. Hammock, Mechanism of Soluble Epoxide Hydrolase. Formation of an a-Hydroxy Ester-Enzyme Intermediate through Asp-333 , J. Biol. Chem. 1995, 270, 26923 - 26930. 

The methanesulfonates (481) of a-hydroxy esters can be converted to the deoxygenated esters (482) in 70 88% yields by indirect electrolysis with PhSeSePh as a recyclable reagent in a divided cell (Scheme 166). The procedure involves the formation of a-phenylselenoester by substitution of the a-methylsulfonyloxyl group with the PhSe followed by displacement of the CK-phenylseleno group with PhSe . The electrolysis is performed in a DMF-NaCl04-(Pt/C) system in the presence of PhSeSePh and ethyl malonate at 50 °C [567]. 

Lemer and Benkovic examined the possibility of performing an intramolecular cyclisation reaction [30]. They chose the formation of a six-membered lactone ring from a hydroxy ester (12) and observed that only one single enantiomer of the 5-lactone (14) in 94% ee was formed from the corresponding 5-hydroxy ester. Moreover, the stereospecific ring closure reaction was accelerated by the antibody -elicited from the transition-state analog 15- by about a factor of 170. 

Under the conditions of iridium-catalyzed hydrogenation, alkyne-carbonyl and alkyne-imine reductive coupling occurs in the absence of stoichiometric byproducts. For example, iridium-catalyzed hydrogenation of nonconjugated alkynes in the presence of ot-ketoesters delivers the corresponding a-hydroxy esters in... 

Scheme 2 Iridium-catalyzed hydrogenation of alkynes in the presence of a-ketoesters to furnish a-hydroxy esters...

In the aldol-Tishchenko reaction, a lithium enolate reacts with 2 mol of aldehyde, ultimately giving, via an intramolecular hydride transfer, a hydroxy ester (51) with up to three chiral centres (R, derived from rYhIO). The kinetics of the reaction of the lithium enolate of p-(phenylsulfonyl)isobutyrophenone with benzaldehyde have been measured in THF. ° A kinetic isotope effect of fee/ o = 2.0 was found, using benzaldehyde-fil. The results and proposed mechanism, with hydride transfer rate limiting, are supported by ab initio MO calculations. 

Deoxygenation of a-hydroxy esters is achieved under milder conditions by reaction of the methanesulphonate with electrochemically generated phenylselenium... 

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