Phosphonium ylides oxidation

Oxidation is an important preparation process in the phosphonium ylide chemistry, which can be performed with a lot of oxidizing agents [29]. 

NMR spectroscopic studies f111,13C, and 31P) are consistent with the dipolar ylide structure and suggest only a minor contribution from the ylene structure.234 Theoretical calculations support this view.235 The phosphonium ylides react with carbonyl compounds to give olefins and the phosphine oxide. 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

Horner reactions of phosphonium ylide and phosphine oxide... 

A series of conjugated polyenes capped with chromophores and containing an androstane spacer were synthesized by Wittig or Wittig-type olefinations from epi-androsterone 5150. For example, vinyl carboxaldehyde 52, prepared from 51 in 60% yield as shown in equation 32, was treated with 9-anthrylmethylphosphonium bromide and n-butyllithium to give diene 53. Exocyclic diene 53 was subsequently oxidized to vinyl carboxaldehyde 54. The androsterone vinyl aldehyde intermediate could either be treated with a tetraphenylporphyrinpolyenyl phosphonium ylide, or, as shown below, the phosphonium salt of the androsterone (55) could be reacted with TPP polyeneal 56. The desired all-(E) isomer, 57, was obtained from the ( )/(Z)-isomeric mixture by chromatographic purification. 

With the fully functionalized heterocyclic core completed, synthetic attention next focused on introduction of the 3,5-dihydroxyheptanoic acid side-chain. This required initial conversion of the ethyl ester of 35 to the corresponding aldehyde through a two-step reduction/oxidation sequence. In that event, a low-temperature DIBAL reduction of 35 provided primary alcohol 36, which was then oxidized to aldehyde 37 with TRAP. Subsequent installation of the carbon backbone of the side-chain was accomplished using a Wittig olefination reaction with stabilized phosphonium ylide 38 resulting in exclusive formation of the desired -olefin 39. The synthesis of phosphonium ylide 38 will be examined in Scheme 12.5 (Konoike and Araki, 1994). 

The metal-free eyclobutane-1,2-dioxime can be generated by oxidative displacement. It is interesting to note that, unlike ketene dimerization, head-to-head dimerization takes place here. The chromium ketenimine complex 20 is prepared by reaction of the Fischer-type chromium carbene complex with alkyl isocyanides.60 A cyclobutane-1,2,3,4-tetraimine 24 has been reported from the reaction of the ketenimine phosphonium ylide 22.61 Bisimine 23 has been proposed as the intermediate in this transformation. 

For reasons similar to those for the oxides2, studies of the bonding in phosphonium ylides have concentrated on the nature of the P=C bond regarding the following issues (i) the strength of the bond, although in reality this has meant its reactivity (see below) (ii) the exact distribution of the electron density with discussions very similar to those for the oxides and (ii) the difference between phosphorus, nitrogen and (to a lesser extent) arsenic ylides. 

Table 4.51. One-Bond (J and Longer-range (2J, 3J, 4J) Carbon-Phosphorus Coupling Constants of Representative Phosphines [372], Phosphonium Salts [365], Phosphine oxides [366, 372, 373], Phosphonium Ylides [365, 373], Phosphonates [368, 372], Phosphites [374], and Phosphates [375] (in Hz). 

D. G. Gilheany, Chem. Rev., 94,1339 (1994). Nod Orbitals but Walsh Diagrams and Maybe Banana Bonds Chemical Bonding in Phosphines, Phosphine Oxides, and Phosphonium Ylides. 

Phosphonium ylides 66 attack 1,2,4-dithiazole derivatives 65 (Y = 0, S) mainly at the S-S bond to give intermediates 67, which can either afford thiazoline derivatives 68 or react further, with a second ylide molecule 66 at the C=Y bond, to finally yield new thiazole and dithiole derivatives 69 and 70. Compounds 70 are predominant in this mixture (yields > 50%). They are oxidized into known dithiole derivatives 71 (Scheme 8) <1993MI33, 1994PS105, 1995PS63, 1999PS393>. 

Review.1 This review covers use of phosphonium ylides, phosphoryl carbani-ons, and phosphine oxide carbanions in synthesis with particular emphasis on (Z)-and (E)-selectivities (558 references). 

The Wittig reaction involves the interaction of an oxo compound (an aldehyde or ketone) (1) with phosphonium ylides [substituted methylene phosphoranes (2a,b)], through an intermediate betaine (3), to yield the appropriate alkene (4) and triphenylphosphine oxide (5), as shown in equation 1. 

Interaction of 4,5 6,7-di-0-cyclohexylidene-2,3-dideoxy-l-C-phe-nyl-L-arafeino-hept-2-enose (65) with phenylmethylenetriphenylphos-phorane was accompanied9 6 by the formation of triphenylphosphine, instead of the expected triphenylphosphine oxide, thus indicating the abnormal character of this reaction. This result may be interpreted as involving possible addition of the phosphonium ylide to the alkenic bond, with subsequent stabilization of the intermediate betaine 82 through elimination of triphenylphosphine, and closure of the three-membered ring2(f) with formation of the cyclopropane derivative 83, as shown in equation 5. 

Thiaoxaphosphetanes are unknown. They have been proposed as intermediates in the addition of sulfur dioxide to phosphonium ylides to give sulfines, in the oxidation of a-phosphinosulfoxides by iodine,and in the reaction of the anticancer alkaloid, acronine, with P4Sio. ... 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

In the Wittig reaction an aldehyde and a phosphonium-ylide are coupled to give a new C=C double bond and triphenylphosphine oxide. Depending on the nature of the phosphonium ylide the Wittig reaction is either Z-selective if a labile ylide is employed or E-selective if a stable ylide is used. A labile phosphonium-ylide PhsP-CH-X possesses a substituent X (e.g. alkyl), which is not able to stabilize the negative charge at the carbon atom, whereas a stable ylide... 

The mechanism of phosphonate anion (135) addition to carbonyl derivatives is similar to the phosphonium ylide addition however, there are several notable features to these anion additions that distinguish the reactions fix)m those of the classical Wittig. The addition of the anion gives a mixture of the erythro (136 and 137) and threo (139 and 140) isomeric p-hydroxyphosphonates (Scheme 24). In the case of phosphine oxides, the initial oxyanion intermediates may be trapped. The anion intermediates decompose by a syn elimination of phosphate or phosphinate to give the alkene. The elinunation is stereospecific, with tile erythro isomer producing the ci.r-alkene (138), and the threo addition adduct producing the... 

Treatment of P-oxido ylides with electrophiles other than proton donors provides a route to stereospecific trisubstituted alkenes. For example, trapping the P-oxido phosphonium ylide B with formaldehyde (generated from paraformaldehyde) leads to dioxido phosphonium derivative D to yield, after elimination of triphenylphosphine oxide, the trisubstituted allylic alcohol... 

Alkylation chemistry has also been reported for alkylphosphine oxides and dialkyl phosphonates. The phosphonate carbanions are often preferred as they offer many advantages over the phosphonium ylides. In particular, the phosphonate group is highly acidifying and the resulting organolithium can be smoothly alkylated. 

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