Enol phosphonium salts

The elimination of the stable PhjPO from enol phosphonium salts 36 can be induced thermally to yield acetylenes. The phosphonium salts are readily prepared on acylation of phosphoranes (equation 104). The pyrolysis of 36 is effective provided that neither nor R is hydrogen, and that R or R is phenyl or acyl, or the... 

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 authors favored a mechanism in which 521 was trapped by (C6H5)3P/l2 to generate the enol phosphonium salt 523 (Scheme 1.143). Loss of triphenylphos-phine oxide from 523 produced the acylimino carbene 524, which cycUzed directly to 522. An alternative mechanistic rationale involving cyclization of 523 to an oxazoline 525 that then eliminated triphenylphosphine oxide to afford 522 was discounted. 

The direct attack on the halogen of a-halocarbonyl compounds by a tertiary phosphine is implicated by substrate reactivity indices (22). The change of venue from the Perkov and Arbuzov pathways concurs with the HSAB rationale as the phosphine P is softer than the phosphite P. Studies on enol phosphonium salt formation (23) support this contention. 

Heterocycles.—The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /9-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig reaction.63 Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphos-phonium salt (61) and sodium carboxylates (Scheme 21).64 Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y—H bond and a carbonyl or nitroso-function, as shown in Scheme 22.65... 

As shown in Scheme 1, aliphatic phosphines such as P(n-Bu)3 catalyze the addition of alcohols (2) to methyl propiolate (3) [35]. The mechanism is believed to involve an initial addition of the phosphine to the C = C moiety to give a zwitterionic allenolate (I), which then deprotonates the alcohol, yielding a vinyl phosphonium salt (II). An alkoxide addition to give an enolate (III), followed by phosphine elimination gives the product 4 and regenerates the catalyst. Several experiments suggest that when alcohols are used in excess, the catalyst rests as the original phosphine [34]. 

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). 

Intramolecular alkylation, although it is enticing, has not been developed as a method for cyclohexanone construction. Joseph P.A. Harrity of the University of Sheffield reports (J. Org. Chem. 68 4392, 2003) that TiCl smoothly transforms the enol ether 10, prepared from the corresponding alkynyl phosphonium salt, into the 2-aryl cyclohexanone 11. Alkynyl ethers such as 10 are readily prepared in enantiomerically-enriched form. Would the enantiomeric excess be maintained on cyclization ... 

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. 

Annelation. Cleavage of l-(trimethylsilyloxy)-2-alkoxycarbonylcyclo-propanes (1) with KF-18-crown-6 generates y-oxo-a-ester enolate anions, which can be trapped by electrophiles. Trapping with a vinyl phosphonium salt results in [3 + 2] annelation to provide annelated cyclopentanones (2).1... 

A possible correlation between the strucmre of the phosphonium salt and polymerization control was investigated. Based on kinetic analysis and NMR data , it was proposed that a fast equilibrium is established between the propagating enolate (46) and a dormant ylide (47) in the polymerization initiated by Ph3CPPh4 (equations 44 and 45). 

The stereoselectivity of the attack of the enolate on the activated cyclopropane most likely is due to steric factors arising from the preferred pseudoaxial conformation of the incipient methyl group . In other words, the approach of the rather bulky phosphonium salt II is less perturbed by the methyl group when it rests on the opposite side of the molecule in the transition state, presumably in the pseudoaxial conformation, as portrayed in IX. This remarkable stereoselectivity has been put to good use in the synthesis of some natural products of the spirovetivane family. ... 

The X-ray structure of the pyramidal and thermally very stable ylid 279, however, rigorously excludes that the cyclopropyl hydrogens of the phosphonium salts 281 and 282 might be less acidic than the isopropyl hydrogens because in the latter the ylid is planar, as is the case with cyclopropyl enolates Does R4P" really lead to a violation of the acidity rule ... 

Enolization plays a role for a number of the acids in Table 3—for example, (MeCO)2CH2 is more than 50% enolized in DMSO [80], and the rate-enhancing effect of enolization is also expected to play a role in the high rate constant in the final entry in Table 3. The other phosphonium salts listed may be regarded as true carbon acids, but Et02CCH2PPh is almost certainly readily enolized with a substantial contribution to the rate constant coming from proton transfer from oxygen. 

Reactions. - The phosphonium salts (287) have been shown to undergo facile nucleophilic displacement of triphenylphosphine on treatment with a range of C, N and S-nucleophiles, giving a range of functional P-substituted silyl enol ethers. The 4-phosphonio-oxazolones (288) undergo dephospho-... 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

---