Enolate. coupling

With a phenol, naphthol or keto-enol coupling component the mechanism is given by Scheme 4.4, in which blocking of the p-position forces coupling at the o-position. In certain cases involving the use of feebly reactive diazonium salts, loss of the proton from the transition state (4-1) in Scheme 4.4 may be slow but may often be facilitated by the addition of a tertiary base, such as pyridine, to the coupling mixture [7,8]. 

Whilst azo compounds prepared from diazonium salts and phenolic or keto-enol coupling components are often depicted in the hydroxyazo form (4.11), an alternative tautomeric structure can be drawn for such compounds (Scheme 4.19). This ketohydrazone tautomer (4.21) can, in cases where the azo and hydroxy groups are located on adjacent carbon atoms, exhibit hydrogen bonding between the two groups as shown. Similar pairs of structures, but without hydrogen bonding, can be drawn for p-hydroxyazo compounds. 

Paquette has reported an intramolecular oxidative coupling using ferric chloride to prepare the intermediate 30 for the synthesis of cerorubenic acid-III. Addition of the dienolate of 28 to FeCls in dmf at —78°C produced the cyclopropane intermediate 29 in 54% yield (equation 16). Although the mechanism of this oxidative cyclization is not discussed in the paper, it is likely that a one-electron transfer pathway is involved. Copper(n) salts have also been utilized for intramolecular enolate coupling, but they proved to be somewhat less effective in the present context. 

For the sake of completeness, it should be mentioned that at variance with the corresponding silyl enolates, the oxidation of titanium bis(enolates) with a variety of oxidants does not show any diastereoselectivity in the formation of the enolate coupling product . On the basis of crossover experiments, it has been shown that the C—C bond formation occurs via an intramolecular route in the case of the silyl derivatives and intermolecularly in the case of the titanium derivatives. 

The titanium enolato complexes shown in Scheme 597 have been used to form intramolecular carbon-carbon bonds through diastereoselective enolate coupling reactions.1550... 

D.1. Reactions with Nucleophiles. Previously, a jr-allylic palladium complex was generated by reaction of palladium reagents with allylic hydrocarbons prior to reaction with nucleophiles. In the catalytic version of this reaction, an allylic halide or an allylic acetate is used with a palladium(O) reagent. Why use a palladium complex when enolate alkylation is a well-known process (sec. 9.3.A) A typical enolate coupling reaction is the conversion of 2-methylcyclopentane-l,3-dione (373) to the enolate anion by reaction with NaOH, allowing reaction with allyl bromide. Under these conditions only 34% of 374 was obtained. When allyl acetate was used in place of allyl bromide in this reaction and tetra w(triphenylphosphino)palladium was used as a catalyst, a 94% yield of 374 was obtained.224 in this reaction, formation of the Jt-allyl palladium complex facilitated coupling with the nucleophilic enolate derived from 373, which exhibited poor reactivity in the normal enolate alkylation sequence. 

Schmitlel M, Burghart A, Malisch W, Reising J, SoUner R (1998) Diastereoselective enolate coupling through redox umpolimg in silicon and titanium bisenolates a novel concept based on intramolecu-larization of carbon-carbon bond formation. J Org Chem 63 396- ... 

A concise synthesis of lycopladine, an unusual and modestly cytotoxic lycopodium alkaloid, illustrates the remarkable ability of this reaction to introduce a carbon substituent at a crowded centre (Scheme 9.62). By virtue of hydroboration-oxidation, the hydroxypropyl substituent can be introduced via allylation. The central five-membered ring can be constructed by sequential conjugate addition and enolate coupling (see Section 2.11). 

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