Esters enamine carboxylic

The conversion of enaminones and enamine carboxylic esters to trifluoroethoxylated 2//-azirines through reactions with PhIO in trifluoroethanol is postulated to proceed via a PhlO-mediated oxidative trifluoroethoxylation and a subsequent azirination of the a-trifluoroethoxylated enamine intermediates. " ... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

Ketones and carboxylic esters can be a hydroxylated by treatment of their enolate forms (prepared by adding the ketone or ester to LDA) with a molybdenum peroxide reagent (MoOs-pyridine-HMPA) in THF-hexane at -70°C. The enolate forms of amides and estersand the enamine derivatives of ketones can similarly be converted to their a hydroxy derivatives by reaction with molecular oxygen. The M0O5 method can also be applied to certain nitriles. Ketones have also been Qc hydroxylated by treating the corresponding silyl enol ethers with /n-chloroperoxy-... 

Use of an interesting enamine photooxidation reaction has teen made of in the synthesis of P-lactams from 2-azetidine carboxylic esters (6.19) 625>. 

Several cycloaddition reactions of 2,5-dihydrothiophene derivatives have been reported. Compounds possessing an enamine system undergo [2 + 2] cycloaddition with acetylene-dicarboxylic ester (Scheme 215) (77AHC(2l)253). Diels-Alder addition of the 2,5-di-hydrothiophene-3-carboxylic ester (557) with butadiene, followed by desulfurization, leads to the trisubstituted cyclohexane (558) (B-74MI31404). 

Certain geminal difluoro groups arc easily aminolyzed yielding imines or enamines.3,20-24 An imine-enamine equilibrium is generally observed,13,25 - 28 which is dependent on the substrate and the amine used. Nevertheless, /i-imino carboxylic esters are predominantly obtained when a-hydrylperfluoro esters (e. g., 4) are reacted with primary amines, while reaction with secondary amines leads to the respective enamines.29,30... 

Formation of Imines or Enamines From a-Hydrylperfluoro Carboxylic Esters General Procedure 2 ... 

Enol ethers are oxidized to carboxylic esters (RCH=CHOR RCH2COOR ) with PCC and enamines to a-amino ketones (R CH=CR2NR R COCR2NR)... 

Aminations of alkyl halides and carboxylic esters are performed with organotin amides, which are also employed for the preparation of enamines (eq (118)) [113],... 

Only a few chiral catalysts based on metals other than rhodium and ruthenium have been reported. The titanocene complexes used by Buchwald et al. [109] for the highly enantioselective hydrogenation of enamines have aheady been mentioned in Section 3.4 (cf. Fig. 32). Cobalt semicorrin complexes have proven to be efficient catalysts for the enantioselective reduction of a,P-unsaturated carboxylic esters and amides using sodium borohydride as the reducing agent [ 156, 157]. Other chiral cobalt complexes have also been studied but with less success... 

Heating is essential for conversion of keto carboxylic esters into amides, as otherwise enamines are formed by reaction of the keto group with the amine773 (cf. pages 507 and 517). 

Studies by Mayer and his school have shown that replacement of the nitrogen group of enamines provides a synthetic method capable of considerable variation and especially useful for the preparation of sulfur heterocycles.486 For example, 3i/-l,2-dithiol-3-thiones are obtained by the action of hydrogen sulfide and sulfur on enamines, particularly in a polar solvent, at room temperature.487 If the sulfur is omitted, then at higher temperatures and in an apolar solvent 2JE7-thiopyrone-2-thiones are formed preferentially.488 Also, enamines can be cleaved to 1,1-dithiols by sulfur 489 enamines obtained from p-oxo carboxylic esters thus give 60-90% yields of / -thioxo carboxylic esters.490... 

Indole-3-carboxylate esters and 3-acetylindoles can be prepared by palladium-catalyzed cycli-zation of enamines (14). These can be prepared from the corresponding anilines by condensation with j8-dicarbonyl compounds or by palladium-catalyzed substitution reactions with ethyl acrylate or methyl vinyl ketone <86BCJ927, 90S215>. Overall yields for the two-step process are 60-80% (Scheme 33). 

In addition to direct formation from an arylhydrazine and a carbonyl compound, iV-aryl-hydrazones can be prepared from aryldiazonium ions by coupling with enolates or enamines (Japp-Klingemann reaction). This reaction has most frequently been applied to j -ketoesters. The coupling product undergoes deacylation so that the ultimate product of Fischer cycUzation is an indole-2-carboxylate ester (Scheme 58) <92JMC4823>. 

Recently, Dominguez de Maria and co-workers [45] have studied experimentally the influence of the organocatalyst on the outcome of the aldol reaction reaction between acetone and isobutyraldehyde. Qrganocatalysts able to form bicyclic oxazolidine intermediates (proUne and prolinol) led predominantly to aldol adducts, while organocatalysts unable to form these oxazolidines (pyrrolidine, O-methyl prolinol and proline tcrt-butyl ester) afforded preferently (>2.5 1) the condensation product. In summary, most of the experimental evidence points toward a distinct catalytic role of oxazoUdinone intermediates in proline-catalyzed reactions. It should be pointed out, however, that DPT studies of the proline-catalyzed self-aldol reaction of propanal, in which the enamine carboxylic acid and the oxazoUdinone pathways were compared, concluded that the Seebach model was inadequate for rationalizing... 

Catalytic asymmetric transamination of i-keto carboxylic esters 94 catalyzed by a chiral base was firstly reported by Soloshonosk et al. [40a] providing an original biomimetic approach to p-fluoroalkyl- 3-amino acids. This transformation involves the formation of A-benzyl enamines 96 in tautomeric equilibrium with A-benzyl... 

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