Stereospecific Ester Activation

II. Stereospecific Ester Activation in Nitrite-Mediated Carbohydrate Epimerization... 

Finally, it is important to mention that there are other related publications in which porphyrin macrocycles are not directly used as dipolarophiles but are transformed into new derivatives that can react with carbonyl ylides via ACE (alkene cyclobutene epoxide) reactions. This idea arose in 1997, when Russell and co-workers found that fused ester-activated cyclobutene epoxides 86 can be ring-opened to give carbonyl ylides 87, and that these can be trapped stereospecifically by ring-strained alicyclic dipolarophiles, such as 2,5-norbomadiene, to form hetero-bridged norbomanes 88 in good yields, through ACE transformations (Scheme 31) <97CC1023>. 

Other systems that allow stereospecific substitution with retention include ester-activated chloride displacement by an amine (25 to 26) and sulfone-activated chloride displacement by azide (27 to 28). The choice of E- or Z-isomers is arbitrary as each gives >98% retention.1 The reactions shown so far do not include carbon nucleophiles. 

Ring-opening reactions with 3-alkylaziridine esters 36 take a similar course. The reactions are in practically all cases regio- and stereospecific with attack at C-3. An important difference is that the aziridine ring needs to be activated by an electron-withdrawing substituent, such as a tosyl or a benzyloxycarbonyl group. In addition, for benzenethiol, indole, and DMF, catalysis with BF3 was necessary (Scheme 22) [31]. 

In Candida sp., degradation of the CoA-alkanoic esters to the alkenoic acid esters is catalyzed by an acyl-CoA oxidase and results in the production of H2O2 that is converted into O2 by catalase activity. The enzyme from C. tropicalis contains FAD (Jiang and Thorpe 1983), and in C. lipolytica carries out a stereospecific antielimination of hydrogen (Kawagnchi et al. 1980). 

When thionophosphonic esters are used for conversion to the phosphonothiochloridates, observation of the stereospecificities of the reactions is possible. Alternative results may be attained through judicious choice of the reagent system. For example, the optically active O-isopropyl methylphosphonothioate, as shown in Equation 4.10, reacts with phosgene at sulfur only to form the O-isopropyl methylphosphonochloridate with inversion of configuration at phosphorus.20... 

Syntheses of naphthyridone derivatives follow the same procedures as those of quinolones, except that substituted 2-aminopyridines (Gould-Jacobs modification) or substituted nicotinic ester/nicotinoyl chloride are used instead of anilines or o-halobenzoic acid derivatives. Most of the recently introduced quinolone antibacterials possess bicyclic or chiral amino moieties at the C-7 position, which result in the formation of enantiomeric mixtures. In general, one of the enantiomers is the active isomer, therefore the stereospecific synthesis and enantiomeric purity of these amino moieties before proceeding to the final step of nucleophilic substitution at the C-7 position of quinolone is of prime importance. The enantiomeric purity of other quinolones such as ofloxacin (a racemic mixture) plays a major role in the improvement of the antibacterial efficacy and pharmacokinetics of these enan-... 

To rationalize the stereospecificity of PLE toward a large variety of monocarboxylic and dicarboxylic esters, Tamm and co-workers have proposed the general formula displayed in Fig. 7.5 [5 5] [67]. Here, no representation of the active site is implied, but the model does rationalize numerous data and allows some qualitative predictions. A qualitative topographical model of the active site of PLE has been proposed by Jones and co-workers [68] [69], As shown in Fig. 7.6, substrate binding is defined by a carboxylate group that interacts with the catalytic serine residue, and by one or two hydrophobic groups that bind to sites 1 and/or 2. 

The stereospecific conversion of sulfinates into sulfoxides of known chirality has been applied as a general method for determining the absolute configuration of a wide range of optically active sulfinic esters. For example, the absolute configurations of a series of alkyl alkanesulfinates obtained by asymmetric synthesis (107) or resolution via 3-cyclodextrin inclusion complexes (106) were determined by this method. 

The reduction of 4-chloroacetoacetate ethyl ester (CAAE) to 4-chloro-3-hydroxy-butanoate ethyl ester (CHBE) usually proceeds stereospecifically [54, 55]. This activity is widely distributed in yeasts, molds and bacteria, most of which give the (S)-enantiomer. Sporobolomyces salmonicolor was found to produce the (l )-enan-tiomer predominantly (62% e. e.) with high molar conversion [54,55], and several Candida yeasts formed (S)-CHBE of high optical purity (> 90% e. e.) [54,55]. 

Compound 211 and several related compounds are readily accessible by stereospecific deprotonation of the appropriate optically active carbamic esters with 5-BuLi/TMEDA ° . Much of the knowledge about the stereochemical course of substitution in benzyUithium derivatives was obtained from experiments with these compounds. Only the reaction with proton acids, aliphatic aldehydes, ketones or esters as electrophiles proceed with retention for alkyl, silyl and stannyl halides, acid chlorides. 

The high regio- and stereospecificity in the rhodium-catalyzed system does not seem to be compatible with the catalytic asymmetric synthesis using a chiral rhodium catalyst, and thus, there have so far been very few reports on the use of chiral rhodium catalysts for the asymmetric allylic alkylation. In 1999, Pregosin and his co-workers first reported asymmetric rhodium-catalyzed allylic alkylation of allylic esters (Equation (48)). Use of optically active... 

In a number of classes of systems, the catalytic and other chemical effects of metal ions on reactions of organic and inorganic molecules are generally recognized the catalysis of nucleophilic reactions such as ester hydrolysis the reactions of alkenes and alkynes in the presence of metal carbonyls (8, 9, 69) stereospecific polymerization in the presence of Ziegler catalysts (20, 55, 56) the activation of such small molecules as H2 (37), 02 (13), H202 (13), and possibly N2 (58) and aromatic substitution reactions of metal-cyclopentadienyl compounds (59, 63). 

Mayer and co-workers improved the amide bond formation of TenBrink s method using unprotected amino alcohols and active esters of bromoalkyl carboxylic acids.[5] More recently, Anthony et al.,[6] and Norman and Kroin[7l reported stereospecific alkylation of acylmorpholinone (Schemes 3 and 4) using sodium hexamethyldisilazanide and lithium diisopropylamide, respectively. 

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