Keto esters regioselectivity

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

A few functional group transformations were necessary to set the stage for the Koevenagel condensation of the p-keto ester 220 (Scheme 33). Ketone 215 was protected as a 1,3-dioxolane. Regioselective hydroboration of the terminal exocyclic double bond was then accomplished with 9-BBN and... 

Reactions of propargylic alcohols with 1,3-cydohexanedione gave 4,6,7,8-tetrahy-drochromen-5-ones in excellent yields with complete regioselectivity (Equation 7.5). Reactions with various six-membered or five-membered ring 1,3-diketones and P-keto esters also gave the corresponding 4,6,7,8-tetrahydrochromen-5-ones and pyranone derivatives, respectively (Scheme 7.22). In contrast, reactions with... 

Asymmetric hydroboration.1 The key step in a synthesis of natural (+ )-hir-sutic add-C (1), based on an earlier synthesis of racemic 1, is an efficient asymmetric hydroboration of the meso-alkene 2. Reaction of 2 with (+ )-diisopinocampheyl-borane (90% ee) followed by oxidation provides the exo-alcohol 3 in 73% yield and in 92% optical purity. Ring expansion of the corresponding ketone with ethyl diazoacetate is not regioselective even in the presence of BF3 etherate or (C2H5)30+ BF4, but does afford the desired a-keto ester in the presence of SbCl5 (8, 500-501). Decarboxylation of the crude product gives (— )-4 in 90% ee after chromatography. 

The ruthenium complex Cp Ru(bipyridyl)Cl has been developed as a catalyst for the first regioselective tandem Michael addition-allylic alkylation of activated Michael acceptors. The net outcome is the decarboxylative insertion of Michael acceptors into allyl /3-keto esters to produce (215). The reaction combines the generation of Ru-tt-allyl and enolate from (213) the enolate is first added to the Michael acceptor (214) and the resulting species is captured by the Ru-tt-allyl.254... 

Carbapenem antibiotics (29) can be manufactured from intermediates obtained by Ru(BINAP)-catalyzed reduction of a-substituted P-keto esters by a dynamic kinetic resolution (Scheme 12.8). 4-Acetoxy azetidinone (30) is prepared by a regioselective RuCl3-catalyzed acetoxylation reaction of 31 with peracetic acid 46 This process has been successful in the industrial preparation of the azetidinone 30 in a scale of 120 tons per year.47 The current process has changed ligands to 3,5-Xyl-BINAP (3c), and 31 is obtained in 98% ee and >94% de (substrate-to-catalyst ratio, or S/C ratio = 1,000).23... 

Regioselective photocyclization of ethylthiopropyl phenylglyoxalate 793, by an electron-transfer process, produced the 1,5-oxathiocin 773 in 96% yield. The mechanism proposed for such a photocyclization involved excitation of the keto ester 793 to its triplet state (T) upon irradiation (350 nm), and electron transfer between the donor and acceptor occurred in T producing the ketyl radical anion (A). This was deactivated to ground state 793 by back electron transfer or was converted to biradical (B) by proton transfer process. Cyclization occurred between the excited carbonyl group and the carbon a to the sulfur on the remote side (Scheme 156) <1997T7165>. 

Keto esters.2 Methyl cyanoformate reacts regioselectively with preformed lithium enolates in the presence of HMPT at -78° to give p-keto esters in generally high yield. Sodium and potassium enolates are unreactive. 

Chiral cyclopentanones.2 The regioselective cyclization of a-diazo-p-keto esters to cyclopentanones (11, 459) is also enantioselective with substrates derived from chiral alcohols. Preliminary studies show that steric factors affect the diastereoselectivity the highest diastereoselectivity is obtained with esters of the alcohol 1, which is available from camphor,3 and in which both the bomane and the naphthalene rings can exert steric effects on the diastereoselectivity. 

The oxidation of a,p-unsatuiated caibraiyl compounds under the usual conditions in DMF using PdCl2/CuCl/02 is very slow. However, regioselective oxidation of oc, -unsaturated esters to p-keto esters (equation IS), and a,p-unsaturated ketones to 1,3-diketones (equation 16) proceeds with NazPdCU in solvents such as 50% acetic acid, isopropyl alcohol, and NMP. r-Butyl hydroperoxide and hydrogen peroxide are used as the reoxidants of the reduced palladium. The reaction proceeds slowly at room temperature but smoothly between 50 and 80 C. Some typical examples of this process are shown in Table 1. 

It is well known that ir-allylpalladium complexes (86) are easily formed by the reaction of PdCb with P. y-unsaturated esters or ketones (85). An attempted oxidation of. y-unsaturated esters and ketones with the PdCl2/CuCl/02 catalyst system in aqueous DMF led to ir-allylpalladium complex formation as the main reaction, and the oxidation of the alkenic bond was hardly observed to a significant extent. However, in aqueous dioxane or THF, the oxidation became the main reaction, giving y-keto esters and 1,4-diketones (87), respectively, with high regioselectivity (Scheme 26).Some results are shown in Table 2. In all cases, no P-keto ester or 1,3-diketone was detected. At the end of the reaction, formation of a considerable amount of the ir-allylpalladium complex (86) was observed. y-Keto esters and 1,4-diketones are useful intermediates for Ae preparation of cyclopentanedione and cyclopentenone, respectively, by base-catalyzed cyclization. Tliis regioselective oxidation provides a unique and efficient synthetic method for y-keto ester and 1,4-diketone synthesis. 

A variety of a-substituted ketones (a-halo, -hydroxy, -methoxy and -amino) have been converted into alkenes by reductive elimination. Obviously, this approach, depends not only on the feasibility of a-functionalization but also on the ability to introduce the a-substituent regioselectively. a-Halo ketones, which are readily prepared from the starting ketone," have been subjected to reductive elimination conditions to afford the desired alkenic products. For example, in the preparation of ( )-eriolanin (Scheme 5)," the protected dihydroxy keto ester is treated sequentially with LDA and Br to afford the a-bromo... 

Condensation of 7-keto-ester hydrazones 475 with the Vilsmeier reagent yielded a general synthesis of l,3-diaryl-4-pyrazoleacetic acid esters 476 (Equation 95) <2005JHC131>. Regioselective addition of lithiated /3-hydrazono-phosphino oxides 477 to isocyanates afforded functionalized hydrazonoamides 478, which were then cyclized to 5-aminopyrazoles 479 with phosphorus oxychloride in the presence of triethylamine (Scheme 56) <1996T4123>. 

In the first step there is chemoselectivity in that the enolate is formed at the centre of the ester and not on the aldehyde. You may not at first think that the aldehyde can form an enoir think again. There is regioselectivity in that the keto-ester could have formed another enolfi reason for all these selectivities is the same the conjugated enolate is much more stable tha . of the alternatives. 

The Schmidt reaction is closely related to the Beckmann reaction (equation 34). Acyclic and cyclic ketones are transformed to amides and lactams by treatment with hydrogen azide. With bridged bi-cyclic ketones, the regioselectivity of the migration is opposite to the direction of the Beckmann reaction. The Schmidt reaction has been applied to asymmetric synthesis starting from optically active a,a-dialkylated -keto esters. High chemical and optical yields have been obtained (equation 35). ... 

The Schmidt rearrangement of optically active a,a-bisalkylated 3-keto esters (161) regioselectively proceeds to give N-acyl a-alkylated a-amino acid esters (162) with retention of configuration and little or no racemization." Acid hydrolysis of (162), followed by treatment with propylene oxide, affords a-alkylated a-amino acids (163) in high yield and optical purity (equation 48). 

Iridoids.1 The first step in a new route to these terpenes involves regioselective sulfenylation of a /1-keto ester (1). This product is converted to the dihydropyrane 6 by the series of steps indicated. 

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