Cyclic keto esters

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). 

Azolo[1,6]naphthyridines. Benzimidazonaphthyridines can be prepared from a one-pot reaction of o-phenylene-diamine, acrolein, and the cyclic keto ester 235 in the presence of molecular sieves and air (Equation 63) <2006SC1671>. 

In the hydrogenation of cyclic / -keto esters (ketones substituted with an al-koxycarbonyl moiety), Ru(II)-binap reduced a racemic substrate in DCM with high anti-diastereoselectivity to give a 99 1 mixture of the trans-hydroxy ester (92% ee) and the ds-hydroxy ester (92% ee), quantitatively [Eq. (18)] [119, 120]. 

Problem 17.39 Ethyl pimelate, CjH,OOC(CH2)5COOCjH reacts with CjH,0 Na (Dieckmaiin condensation) to form a cyclic keto ester, CjHj Oj. Supply a mechanism for its formation and compare the yields in ethanol and ether as solvents. ... 

PdLX complex undergoing insertion of the coordinated double bond into the a-Pd-carbon bond to form a Pd-alkyl intermediate. With 1,4-penta-diene and 1,5-hexadiene, cyclic keto esters are formed in MeOH and a similar cyclic mechanism is suggested involving insertion of the coordinated double bond into the acyl Pd complex intermediate (16). Although CO pressures of 1000 atm were used, these cyclic ketones were produced also at 250 atm in the presence of p-toluene sulfonic acid, but no details were reported. 

Interestingly, cyclic / -keto esters, e.g. 69, can be also fhiorinated with enantioselectivity up to 80% ee, although the yield and enantioselectivity depend strongly on the type of substrate. A representative example of asymmetric fluorination of a cyclic ester is shown in Scheme 3.27, Eq. (2). In addition, oxindoles 71 have been successfully fhiorinated, as shown in Scheme 3.27, Eq. (3). Under optimized conditions, the desired 3-substituted 3-fluorooxindole, 72, was obtained in 79% yield and with enantioselectivity of 82% ee. 

The synthesis may thus be seen to be an intramolecular Claisen ester condensation, which is known as the Dieckmann reaction. The procedure is an important method for the synthesis of five- and six-membered ring systems, and the cyclic / -keto ester product may be converted into the corresponding cyclic ketone by hydrolysis followed by decarboxylation (ketonic hydrolysis, see Section 5.8.5, p. 619). The base catalyst used in Expt 7.8 is sodium ethoxide, but sodium hydride as a 50 per cent dispersion in oil is a recommended alternative. 

In the absence of the MeaSiCI, the main product from this reaction becomes the cyclic keto-ester below, which arises from base-catalysed Dieckmann cyclization (see Chapter 28) of the diester. 

Ethyl 2-oxocyclohexane-carboxylate la cyclic -keto ester)... 

Intramolecular Claisen condensations can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones (Section 23.6). Called the Dieckmann cyclization, llie reaction works best on 1,6-diesters and 1,7-diesters. Intramolecular Claisen cyclization of a 1,6-diester gives a tiive-membered cyclic /3-keto ester, and cyclization of a 1,7-diestcr gives a six-membered cyclic -keto ester. 

The only trap is in the reduction of the cyclic keto-ester where you need to recall that NaBH4 reduces ketones but doesn t reduce esters. Correct identification of functional groups matters. 

Loss of alkoxide ion from the tetrahedral intermediate fanas a cyclic -keto ester. 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product- Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benxoate and ethyl formate, for instance) sind thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmaan cyclization reactions, provide excellent syntheses of five- and six-membered cyclic -keto esters starting from 1,6- and 1,7-diesters. 

Mechanism of the Dieckmann cyclization of a 1,7-diester to yield a cyclic -keto ester product. 

Table 17. Krapcho reaction of -cyclic keto esters...

Phenols react with P-keto-esters, including cyclic keto-esters, to give coumarins under acid-catalysed conditions - concentrated sulfuric acid, hydrogen fluoride, a cation exchange resin, indium(III) chloride and sulfamic acid (solvent free) are amongst those that have been used. 

Figure 15-44. Diastereoselective reduction of cyclic keto esters 24S. ...

Enantio- and diastereoselective reduction of cyclic keto esters are also achieved using various microorganisms (Fig. 15-44) 245]. By selecting a suitable organism, syn-and anti-hydroxyesters may be synthesized enantio- and diastereoselectively. 

Oxidative cyclization gives radical 32 oxidation of 32 gives 33, probably as a mixture of double bond positional isomers. The unsaturated cyclic -keto ester 33 is more acidic than 31 and is rapidly oxidized further by two equivalents of Mn(III) to give a cyclohexadienone that tautomerizes to phenol 34. The overall reaction consumes four equivalents of Mn(OAc)3. 

The formation of esters from cyclic / -keto esters is necessarily combined with ring opening. Thus ethyl 2-(hydroxyimino)adipate is obtained from ethyl 2-oxocyclopentanecarboxylate on its reaction with ethyl nitrite and sodium ethoxide.263 If the ester group is hydrolysed under... 

The tautomeric form of 4-hydroxycoumarin (103), acting as a cyclic ) -keto ester, was condensed with aldehydes and urea or thiourea in the presence of basic alumina by heating for 4-6 h at 110-120 °C to give benzopyrano[4,3-[Pg.85]

The spectrometric and chiroptical properties of vinylogous urethane derivatives of L-alanine and L-phenylalanine methyl esters (70) can be ascertained from the reaction of a-amino acid esters with cyclic ) -keto esters (Tortorella and Tangari, 1973). These chromophores show strong uv... 

Diphenyl prolinol silyl ether (123a) has been employed as a catalyst for the Michael-Michael cascade reaction of the /3-dicarbonyl Michael donor (155) and Q, /i-unsaturated aldehydes (156), giving rise to functionalized cyclic keto esters (157) with <32 1 dr and <99%... 

The ketone moiety of a cyclic keto-ester need not be in conjugation with the carboxyl moiety. This allows other methods for introduction of the amine group. Conversion of R-7.127 (resolved from the racemic material with brucine) to its oxime (7.128) was accomplished by treatment with hydroxylamine and pyridine.20... 

Scheme 5.35 outlines the first four steps and Scheme 5.37 the final steps of fliis synthesis. Cyclic keto ester 5 is easily available by Dieckmann condensation... 

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