Keto esters acyclic

Davis et al.111 developed another method for reagent-controlled asymmetric oxidation of enolates to a-hydroxy carbonyl compounds using (+)-camphor-sulfonyl oxaziridine (147) as the oxidant. This method afforded synthetically useful ee (60-95%) for most carbonyl compounds such as acyclic keto esters, amides, and a-oxo ester enolates (Table 4-20). 

Stereoselective hydrogenation.3 Hydrogenation of the cyclic P-keto ester 2 catalyzed by an (R)-BINAP-Ru complex (1) proceeds with high nnri-diastereoselec-tivity to give a 99 1 mixture of 3 and 4. On the other hand, catalytic hydrogenation of the acyclic keto ester 5a proceeds with no appreciable resolution to give a 1 1... 

An interesting intermolecular version of this reaction has likewise been put forward for the preparation of seven-, eight-, and nine-mem-bered carbocycle, as illustrated with a sole example in Scheme 3 [7]. In contrast to the above, these reactions begin with a carbonyl addition reaction of chloroiodoalkanes to cyclic or acyclic keto esters leading to the formation of an intermediate lactone. An intramolecular nucleophilic acyl substitution then terminates the sequence. The example in Scheme 3 represents a simple method for the construction of the 5 8 5 tricyclic ring system. 

Derivatives of the type of (250) have also been obtained by the use, as the AB component, of unsubstituted oj-tetralone or, as the D component, of acetylcyclohexene [359, 361, 362, 364-367]. Attempts to use acyclic keto esters in the reaction with (8) and their subsequent cyclization were unsuccessful [368] likewise, bicyclie ketones not containing an aromatic... 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Another approach in the use of chiral S/P ligands for the hydrosilylation reaction of ketones was proposed more recently by Evans et Thus, in 2003, these workers studied the application of new chiral thioether-phosphinite ligands to enantioselective rhodium-catalysed ketone hydrosilylation processes. For a wide variety of ketones, such as acyclic aryl alkyl and dialkyl ketones as well as cyclic aryl alkyl ketones and also cyclic keto esters, the reaction gave high levels of enantioselectivity of up to 99% ee (Scheme 10.44). 

This chemistry is applicable to the hydrogenation of acyclic compounds such as a-acylamino-, a-ammonio-, a-amidomethyl-, and a-chloro-substituted / -keto esters (Fig. 32.26) [14n, 74a, 77-79]. The (R)-BINAP-Ru-catalyzed hydrogenation of the a-acylamino and a-amidomethyl ketones in CH2C12 leads to the 2S,3R (syn) alcohols in up to 98% ee [14n, 74a]. The use of sterically hindered... 

Fig. 32.26 Hydrogenation of acyclic a-substituted yfi-keto esters via dynamic kinetic resolution.

Jorgensen s group44a carried out the reaction using the anhydrous form of chiral bis(oxazoline) coordinated copper complex. Complex 106 containing 83 as the chiral ligand was found to be the most effective. As shown in Scheme 5-32, the asymmetric hetero Diels-Alder reaction of //.y-unsaturated a-keto esters with acyclic enol ethers results in products with excellent yield and enantioselectivity. 

There are few cases in which free /3-aldehydo esters have been condensed successfully with ureas. Commonly, alkoxymethylene esters are used. The initial reaction leads to an acyclic intermediate that may require a separate treatment to induce ring closure. The reaction of a /3-keto ester with urea may be a two-step process in which case acid catalysis can be used in the formation of an acyclic intermediate, with ring closure effected by strong alkali. When the ester component is a lactone or chromone, the product contains a hydroxyalkyl <2000JME3837> or 2-hydroxyphenyl substituent <2004S942>, as shown by the synthesis of the 5-(2-hydroxyethyl)-4-pyrimidinone 657 and the 6-(2-hydroxyphenyl)-pyrimidine 659. 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Condensation of a /3-keto ester with 1,3-dibromopropane gives the bromoketone, e.g. (232), which on hydrolysis yields a mixture of equal quantities of 2-methylpyran-2-ol and the acyclic ketone (233 Scheme 55) (79JOC364). 

The conjugate addition of cyclic or acyclic a-substituted ft-keto esters to cy,/3-unsaturated ketones can be achieved with good diastereo- and enantio-selectivity (<98% ee) by using derivatives of Cinchona alkaloids, such as (104), a chiral organo-catalysts.155... 

Mteto esters can be obtained by acylation of enamines of acyclic and cyclic ketones with ethyl chloroformate3. Surprisingly no /J-keto ester was obtained when the reaction was carried out in the presence of triethylamine and an extra mole of enamine or a tertiary aromatic amine must therefore be used to neutralize the acid liberated The intermediate enamino ester can be isolated and reduced by hydride donors225 (Scheme 92). 

The phorphorus betaine method is recommended for inversion of the stereochemistry of acyclic di- and Irisubstituted alkencs. Highly hindered epoxides react very slowly with LDP and alkenes arc not obtained in good yield. Keto groups interfere with the sequence owing to enolate formation unless 2 eq. of reagent is used. Epoxy esters cannot be dcoxygenated in practical yield. 

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). ... 

Amines and -keto carbonyl compounds form enamines in high yields. This reaction has been used to protect amino acids and amino acid esters (Scheme 17). Enamines (28) from acyclic P-dicarbonyl com-... 

---