Ketones enol phosphonium salts

Preparation.—The reaction of triphenylphosphine with 1-bromoalkyl ketones has been described in which the initially formed labile enolic salts (59) are converted irreversibly into phosphonium salts via ion-pairs (Scheme 4). When R is larger than ethyl the ion-pair is not formed and the enol salts decompose in the pr ence of atmospheric moisture to give alkyl aryl ketones. No enol phosphonium salts are isolated from the reaction of bromo-diketones with triphenylphosphine in ether. The phosphonium salts (60) are precipitated directly. 

The phosphonium salt 2 reacts similarly with enolates to give vinyl sulfides. The vinyl sulfide group can then be hydrolyzed to a ketone. The overall transformation corresponds to the reactivity of the dipolar synthon C (page 841). 

Bicycloannelation.1 The a -enolate of an a,j -cyclohexenone reacts with this phosphonium salt to form a tricyclof3.2.1,0 ]octane in low to moderate yield. This reaction was used in a short synthesis of the pcntacyclic dilcrpcnc trachyloban-19-oic acid (4). Reaction of the lithium enolale of 2, prepared from podocajpic acid, with I provided the pcntacyclic ketone 3, which was reduced by the Wolff-Kishncr reaction to 4. 

In contrast to a,(3-unsaturated phosphonium salts, ot,(3-unsaturated phosphonates (161)1331 alkylate ali-cyclic ketone enolates efficiently, while the homologous diethyl butadiene phosphonate (162)133bintramolecular cyclization. Heathcock reports that... 

Wittig reagents can represent enolates of unsymmetrical ketones. From Corey s work on arachidonic acid metabolites18 comes the coupling between the aldehyde 92 and the phosphonium salt 93. This is very impressive as both components have multiple functionality and there is no loss of stereochemical integrity even though the Wittig reaction is done in aqueous NaOH. 

A device for getting extended enolates of esters to combine with aldehydes and ketones in the y position is to use a Wittig approach. The bromo-ester 28 is commercially available. Reaction with a trialkyl phosphite gives the phosphonate ester 29 that gives dienes such as 30 with aldehydes.11 Phosphonium salts can also be used.12... 

The extra stabilisation makes the ylid rather unreactive and phosphonate esters 91 are often used instead of phosphonium salts in these reactions. Treatment with a base (NaH or RO is often used, BuLi will certainly not do) gives an inherently more reactive enolate anion 92 rather than an ylid. These Horner-Wadsworth-Emmons reagents (H WE as we shall call them, though they go under many other names) react with ketones as well as aldehydes and the product is normally the E-alkcnc16 93. 

Indoles and Carbazoles. - Formation. 2-Arylindoles (132) are formed by intramolecular Wittig reaction of the phosphonium salts (131). The hydroxamic acids PhN(OH)COCH2COR (R = alkyl or aryl) cyclize in boiling toluene to mixtures of indoles (133) and 3-isoxazolones (134). Irradiation of a solution of o-iodoaniline and the potassium enolate of acetone affords 2-methylindole. The enamino-ketone (135) cyclizes photochemically to 1,2-dimethylindole (136) with elimination of acetaldehyde/ The styrene derivative (137), obtained by the action of Meerwein s acetal, Me2NCH(OMe)2, on o-nitrotoluene, yields 1-hydroxyindole on treatment with zinc/ Azidobenzocyclobutanes (138 R = Me, Ph, or CH2Ph) are converted into indoles (133) by the action of concentrated sulphuric acid/ ... 

It is not clear whether enolization is avoided under the lithium-free, high-concentration conditions, or whether it occurs reversibly enough to permit eventual conversion of the ketone to the alkene. However, the most successful procedures involve alkoxide bases (159, 168-170) or require the presence of excess phosphonium salt (171). Proton exchange and reversible enolate formation are likely under these conditions, and aldol condensation pathways would also be reversible when potassium or sodium bases are used. Thus, excellent yields of alkenes are possible with the most hindered substrates, provided that other pathways for irreversible enolate decomposition are not available. 

This chapter will discuss carbanion-like reactions that utilize enolate anions. The acid-base reactions used to form enolate anions will be discussed. Formation of enolate anions from aldehyde, ketones, and esters will lead to substitution reactions, acyl addition reactions, and acyl substitution reactions. Several classical named reactions that arise from these three fundamental reactions of enolate anions are presented. In addition, phosphonium salts wiU be prepared from alkyl halides and converted to ylids, which react with aldehydes or ketones to form alkenes. These ylids are treated as phosphorus-stabilized car-banions in terms of their reactivity. 

Cyclohexene annelation.1 Reaction of ketone enolates with 2 equiv. of this salt results in two sequential Michael reactions to give a cyclohex-enyl(triphenyl)phosphonium bromide, which can be hydrolyzed to a cyclohex-enyl(diphenyl)phosphine oxide.1... 

---