Cyclic /?-ketoesters

Crossed Claisen reactions with two different esters, each of which has a-H atoms, are seldom useful synthetically as there are, of course, four possible products. Crossed Claisen reactions are, however, often useful when one of the two esters has no a-H atoms, e.g. HCOzEt, ArC02Et, (C02Et)2, etc., as this can act only as a carbanion acceptor. Such species are in fact good acceptors, and the side reaction of the self-condensation of the other, e.g. RCH2C02Et, ester is not normally a problem. Intramolecular Claisen reactions, where both C02Et groups are part of the same molecule [e.g. (123)], are referred to as Dieckmann cyclisations. These work best, under simple conditions, for the formation of the anions of 5-, 6- or 7-membered cyclic / -ketoesters... 

Intramolecular reactions are very favourable here as elsewhere and the cyclic ketoester 41 can be disconnected to the symmetrical diester 42. The cyclisation works well.12 In these reactions the proton between the two carbonyl groups of the product (marked in 41) is removed by the ethoxide formed in the reaction to give the stable enolate 43. This is easily demonstrated by adding an alkyl halide in the work-up when products 44 are formed. 

Dowd and coworkers have ingeniously ring-expanded twelve-, fourteen- and fifteen-membered cyclic / -ketoesters using the following sequence. Reaction of the anion of the / -ketoester with diiodomethane followed by treatment with tributyltin hydride with AIBN, in benzene under reflux, gives a one-carbon ring expansion (equation 137)810. 

Some nonconjugated dienes are converted to cyclic ketoesters. 5-Aiyl-1,2,4-oxadiazoles are formed in the carbonylation of aryl halides when RC(=NOH)NH2 are present. 

The reactions of lithiated anions of chiral hydrazones 1.76 (Samp, Ramp) with a,P unsaturated esters or sulfones are highly stereoselective at -78°C. By a sequence of 1,4-addition and removal of the chiral auxiliary with O3, Enders and coworkers [161, 1441, 1442, 1443] prepared 5-keto-3,4-dialkylesters and 5-keto-3-alkylsulfones with high selectivities (figure 7.60). When -bromo-a,P-un-saturated esters or sulfones are used as Michael acceptors, cyclic ketoesters or... 

Problem 17.32 Ethyl pimelate, C2H5OOC(CH2)5COOC2H5, react C2H50 Na+ (Dieckmann condensation) to form a cyclic ketoester, C9H1403. Supply a mechanism for its formation and compare the yields in ethanol and ether as solvents. 

A new application of the Schmidt rearrangement is to give unnatural aminoacids <91BMC125>. Treatment of the optically active cyclic -ketoester (266) with hydrazoic acid gives the optically active azepinone (267) which upon selective reduction with diborane furnishes the novel cyclic amino acid ester (268) (Scheme 36). 

In the absence of the MejSiCI, the main product from this reaction becomes the cyclic ketoester below, which arises from base-catalysed Dieckmann cyclization (see Chapter 25) of the diester. 

In 2010, Zhong and co-workers [32] tried a similar approach using nitrotyrenes and cyclic ketoesters. The reaction occurs through a Michael-Henry cascade reaction catalyzed by bifunctional thiourea catalysts derived from cinchona alkaloids. The reaction furnished the desired bicyclic products 43 in good yields and excellent stereoselectivities (Scheme 10.14). 

In 2009, McGarraugh and Brenner [53] reported the reaction of cyclic ketoesters like 81 with enals catalyzed by VII. The reaction undergoes a Michael-Michael cascade reaction and furnish the cyclohexene derivatives 82 in good yields and excellent stereoselectivities. 

Scheme 60 Copper-peptide-catalysed ECA of organozinc reagents to activated cyclic ketoesters by Hoveyda [92]...

Scheme 65 Copper-NHC-catalysed ECA of dialkylzinc reagents to cyclic ketoesters by Hoveyda...

In the current numbering of chlorophylls, the two carbons of the cyclic ketoester are numbered 13 (connected to carbon-13) and 13 (coimected to carbon-15). For more information, consult the page of lUPACs Website devoted to the nomenclature oftetrapyrrolic compounds. 

An efficient protocol for enantioselective trifluoromethylation of cyclic / -ketoesters has been developed via Cu-boxmi (6) catalysis. Both five- and six-membered ring 0-ketoesters have been converted to the corresponding products in high yields with up to... 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Cyclic a-halomethyl or a-phenylselenenylmethyl (3-ketoesters undergo one-carbon ring expansion via transient cyclopropylalkoxy radicals.360... 

Organo copper and lithium enolates of cyclic ketones, lactones, and lactams or acyclic ketones are converted with acylimidazoles or imidazole-N-carboxylates into the corresponding / -diketones or / -ketoesters ... 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

One-pot syntheses of 1,4-diketones, y-oxoaldehydes, y-ketoesters, and co-oxoalkanoates have been reported by bond cleavage of cyclic a-nitroketones with KOH in methanol and subsequent Nef reaction (Section 6.1) with KMn04 (Eq. 5.16).31... 

Dealkoxycarbonylation of activated esters occurs classically under drastic thermal conditions [90]. It constitutes a typical example of a very slow-reacting system (with a late TS along the reaction coordinates) and is therefore prone to a microwave effect. The rate determining step involves a nucleophilic attack by halide anion and requires anionic activation, which can be provided by solvent-free PTC conditions under the action of microwave irradiation [91]. The above results illustrate the difficult example of cyclic /1-ketoesters with a quaternary carbon atom in the a position relative to each carbonyl group (Eq. 36). 

This type of reaction is usually best performed in DMSO solution. A simpler procedure has been proposed which uses anionic activation and microwave irradiation, with a metallic salt as the reagent and a PTC in the absence of solvent [75], This procedure was applied to the striking example of cyclic /J-ketoesters with considerable improvements (Eq. 53 and Tab. 5.25) which are readily apparent when the maximum yields obtained under classical Krapcho conditions (<20% when R-H) are considered [76],... 

Ojima (43) used the same DIOPRh catalyst earlier to add Et2SiH2, PhMeSiH2, Ph2SiH2 and a-naph-PhSiH2 to a-ketoesters to synthesize optically active a-hydroxy carboxylate esters. With diethyl- or phenyl-methylsilane and propyl pyuvate, a double hydrosilation occurred to chiefly make a cyclic product with double asymmetry. 

A new stable sulfenylating reagent 3-phenylsulfenyl-2-GV-cyano-imino)thiazolidine 57 has been described. It reacts with amines or thiols to give sulfenamides or disulfides in excellent yields. a-Sulfenylation of carbonyl compounds also proceeds smoothly and if an optically active 4-diphenylmethyl substituent is attached to the thiazolidine ring (58), the cyclic (3-ketoester 59 can be sulfenylated in high yield with an ee of 96% to give the sulfide 60 <00SL32>. 

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