Keto-esters, reaction with

In this reaction, sodium metal is reacted with absolute alcohol to make sodium ethoxide (NaOCH2CH3). Ethyl acetoacetate and bromobenzene are then added to this to produce a beta keto ester. Reaction with acid then produces phenylacetone. 

Our development of the catalytic enantioselective inverse electron-demand cycloaddition reaction [49], which was followed by related papers by Evans et al. [38, 48], focused in the initial phase on the reaction of mainly / , y-unsaturated a-keto esters 53 with ethyl vinyl ether 46a and 2,3-dihydrofuran 50a (Scheme 4.34). 

A piridazine ring forms the nucleus for a rather unusual nontricyclic antidepre.ssant. Condensation of the keto ester 136 with hydrazine leads to the cyclic hydrazide 137. Oxidation, for example with bromine, gives the corresponding pyridazone 138. The oxygen is then replaced by chlorine by reaction with phosphorus oxychloride. Displacement of the halogen in 139 with N-ethylami-nomorpholine affords minaprine 140 [30]. 

Reactions with Carboxylic Acid Esters Alkyl nitrones can be metallized upon treatment with phenyl lithium in ether solution. The Li-derivatives react with carboxylic acid esters to give 3-oxo nitrones (305)- the analogs of 3-diketones and j3-keto esters (545). With the help of the 13C NMR method it has been found that 3-oxo nitrones (305) exist as an equilibrium mixture... 

Three-cmbon ring expansionThe cyclic p-keto esters 1 with a 4-oxopentyl group at the a-position do not undergo the expected aldol condensation on treatment with KOC(CH3)3 in DMSO, but undergo ring expansion to medium-size ketones (2). The reaction may involve aldol and retro-aldol condensation. A similar... 

The pyrido[2,3-, pyrimidines 560 and 562 were prepared as analogues of the multitargeted antifolate (MTA) by the reaction of /3-keto ester 558 with either 2,4-diamino-6(l//)pyrimidinone 490 or 2,4,6-triaminopyrimidine 466, followed by saponification of the resulted glutamate products 559 and 561, respectively (Scheme 25) <1997H(45)2229>. 

Related to simple chain extension is ring expansion and contraction useful because some ring sizes are easier to make than others. So available cyclohexanone can be expanded into cycloheptanones such as the useful keto-ester 20 with an activated position for enolate reactions. The reagent is ethyl diazoacetate 18 readily available from glycine esters. Addition to the ketone 18 automatically... 

An hDA reaction between Danishefsky s diene and glyoxylate esters proceeds in the presence of bisoxazoline-lanthanide complexes with moderate levels of enantioselectivity <2000TL2203>. A similar reaction between Danishefsky s diene and a-keto esters proceeds with excellent enantioselectivity in the presence of bisoxazoline-copper <2001TL6231, 2003EJ0317, 2004TA1987> or Cr(m), Co(n and m)-salen complexes <2004TA3189>. 

Hydantocidin, which bears a spiro skeleton, is a natural product and a herbicide. Eq. 3.113 shows the typical preparation method of spiro-diketone (277) from the reaction of a-diazoketone (276) with Rh2(OAc)4 via a carbenoide species. However, this spiro skeleton can be also constructed by radical reactions. Treatment of (3-keto ester (278) with Mn(OAc)3 in the presence of electron-rich olefin generates spiro-cyclic thioketal (279) through the formation of a (3-keto ester radical, intermolecular radical addition to... 

As an oxidative cascade reaction with Mn(OAc)3, treatment of tetra-olefinic (3-keto ester (308) with Mn(OAc)3 in acetic acid generates a steroidal skeleton (309) via quartet 6-endo-trig ring closure, in one-pot reaction (eq. 3.129). 

The selective reduction of the 8-hydroxy- 3-keto ester 4 with Me4NBH(OAc)3 afforded the corresponding l,3-anft -diol in 87% yield and 14 1 diastereoselectiv-ity. The 1,3-anti -diol was protected as the acetonide 5, followed by a Pd-catalyzed coupling reaction with the vinyl iodide 6 to provide the diene 7 in 69% yield. Reduction of the ester, Swem oxidation, and finally, Wittig olefination afforded the (Z)-vinyl iodide 8. 

The idea of coupling two keto-esters together with a nitrogen atom also works for pyridines except that an extra carbon atom is needed. This is provided as an aldehyde and another important difference is that the nitrogen atom is added as a nucleophile rather than an electrophile. These are features of the Hantzsch pyridine synthesis. This is a four-component reaction that goes like this. 

For the enantioselective hetero Diels-Alder reaction, very similar bis(oxazoline) complexes proved to be highly efficient [28]. The conversion of several unsaturated keto-esters 59 with ethyl-vinyl ether 60 gave cycloaddition products 61 in 97-99% ee. 

In their enantioselective total synthesis of (+)-triptocallol (3-79), a naturally occurring terpenoid, Yang and coworkers made use of a concise Mn(OAc)rmediated and chiral auxiliary-assisted oxidative free-radical cyclization [39]. Reaction of 3-77, bearing a (R)-pulegone-based chiral auxiliary, with Mn(OAc)3 and Yb(OTf)3 yielded tricyclic 3-78 in a twofold ring closure in 60% yield and a diastereomeric ratio of 9.2 1 (Scheme 3.20). A further two steps led to (-i-)-triptocallol (3-79). For the interpretation of the stereochemical outcome, the authors proposed the hypothetical transition state TS-3-80, in which chelation of the (3-keto ester moiety with Yb(OTf)3 locks the two carbonyl groups in a syn orientation. The attack of the Mn -oxidation-generated radical onto the proximate double bond is then restricted to the more accessible (si)-face, as the (re)-face is effectively shielded by the 8-naphthyl moiety. 

Hydroxylation of a -keto ester. Reaction of the unsaturated 3-keto ester 1 with m-chloroperbenzoic acid gives the expected epoxide in 88% yield. Reaction with excess peracid unexpectedly also effects hydroxylation to provide 2 in high yield. 

Treatment of a P-keto ester direedy with peracid has been shown in one case (Itf to effect quantitative a-hydroxylation. Presumably this arises through epoxidation of the enol. Peracid reactions of this kind will be discussed in more detail in Section 2.3.2.1.3.i. Oxidations of the enols of P-keti> esters to the a-hydroxy derivatives using singlet oxygen in the presence of fluoride ion occurs in moderate yield through an ene process (Section 2.3.2.1.3.ii). 

We wondered if this reaction might be exploited to construct the angularly condensed benzo[a]anthracenes. A problem was the aromatization of the initially formed hydroaromatic ring A under the relatively drastic basic reaction conditions. The starting material 12 was synthesized in a stepwise manner from l-hydroxy-5-methoxy-9,10-anthraquinone [23]. The crucial cyclization can mechanistically be regarded as an intramolecular nucleophilic displacement of the methoxy group to afford a keto ester 13 with about 55% yield (Scheme 5). Only a few nucleophilic additions to electron-deficient anthraquinones are known [20,24,25] and intramolecular reactions of this type are more facile [21, 26-30]. The subsequent ethoxydecarbonylation under acidic conditions to yield ketone 14 presented no problem. 

Keto esters react with arylenediamines when heated in neutral solvents to give benz-imidazolinones in a reaction which is capable of extension to the jS-keto esters derived from cyclic ketones. Under acidic conditions, o-phenylenediamine gives a 78% yield of... 

For example, reaction of an ester enolate with diethyl carbonate yields a p-diester (Reaction [1]), whereas reaction of a ketone enolate with ethyl chloroformate forms a p-keto ester (Reaction [2]). 

---