Phosphonium salts alkenes

The isoxazoles (585) were formed regioselectively from the (dioxoalkyl)phosphonium salts (584) with hydroxylamine hydrochloride, the direction of cyclization being different from that of the nonphosphorus-containing 1,3-dioxo compound (see Chapter 4.16). Aqueous sodium hydroxide converted (585) into the isoxazole (586) and triphenylphosphine oxide. Treatment of (585) with n-butyllithium and an aldehyde gave the alkene (587). With hydrazine or phenylhydrazine analogous pyrazoles were formed (80CB2852). 

In the Wittig reaction an aldehyde or ketone is treated with a phosphorus ylid (also called a phosphorane) to give an alkene. Phosphorus ylids are usually prepared by treatment of a phosphonium salt with a base, and phosphonium salts are usually prepared from the phosphine and an alkyl halide (10-44) ... 

The overall sequence of three steps may be called the Wittig reaction, or only the final step. Phosphonium salts are also prepared by addition of phosphines to Michael alkenes (hke 15-8) and in other ways. The phosphonium salts are most often converted to the ylids by treatment with a strong base such as butyllithium, sodium amide, sodium hydride, or a sodium alkoxide, though weaker bases can be used if... 

Wittig reactions are versatile and useful for preparing alkenes, under mild conditions, where the position of the double bond is known unambiguously. The reaction involves the facile formation of a phosphonium salt from an alkyl halide and a phosphine. In the presence of base this loses HX to form an ylide (Scheme 1.15). This highly polar ylide reacts with a carbonyl compound to give an alkene and a stoichiometric amount of a phosphine oxide, usually triphenylphosphine oxide. 

This accounts for the considerable discrepancy between the alkene Z/E ratio found on work-up and the initial oxaphosphetan ais/trans ratio. By approaching the problem from the starting point of the diastereomeric phosphonium salts (19) and (20), deprotonation studies and crossover experiments showed that the retro-Wittig reaction was only detectable with the erythreo isomer (19) via the cis-oxaphosphetan (17). Furthermore, it was shown that under lithium-salt-free conditions, mixtures of (19) and (20) exhibited stereochemical drift because of a synergistic effect (of undefined mechanism) between the oxaphosphetans (17) and (18) during their decomposition to alkenes. 

This is an extremely useful reaction for the synthesis of alkenes. It involves the addition of a phosphonium ylid, e.g. (136), also known as a phosphorane, to the carbonyl group of an aldehyde or ketone the ylid is indeed a carbanion having an adjacent hetero atom. Such species are generated by the reaction of an alkyl halide, RR CHX (137), on a trialkyl- or triaryl-phosphine (138)—very often Ph3P—to yield a phosphonium salt (139), followed by abstraction of a proton from it by a very strong base, e.g. PhLi ... 

The olefin metathesis of 3-hydroxy-4-vinyl-l,2,5-thiadiazole 112 and a McMurry coupling reaction (Ti3+ under reductive conditions) of the aldehyde 114 were both unsuccessful <2004TL5441>. An alternative approach via a Wittig reaction was successful. With the use of the mild heterogenous oxidant 4-acetylamino-2,2,6,6-tetramethyl-piperidine-l-oxoammonium perfluoroborate (Bobbitt s reagent), the alcohol 113 was converted into the aldehyde 114. The phosphonium salt 115 also obtained from the alcohol 113 was treated with the aldehyde 114 to give the symmetrical alkene 116 (Scheme 16) <2004TL5441>. 

In the phosphonium salt synthesis, the addition reaction of tertiary phosphines to activated alkenes has been reported (Scheme 3). PPh3 is added to electron-deficient alkenes such as enones or enals at the p-position in the presence of acids.4 The reaction of styrenes with phosphine has recently been reported by Okuma, which gave Markovnikov adducts.5 Although no catalyzed reactions of... 

Before examining the reaction of deactivated alkenes, the phosphonium salt synthesis was applied to 1,3-dienes.21 When ( )-6-phenyl-l,3-hexadiene was treated with equimolar amounts of PPh3 and CF3S03H in the presence of RhH(PPh3)4 (2.5 mol%) in THF at 0 °C for 3 h, ( )-(6-phenyl-3-hexenyl)triphenylphosphonium salt was obtained in 89% yield after anion exchange with LiPF6 and recrystallization (Scheme 16). The addition of phosphine and hydrogen occurred at the 1- and 2-carbon atoms of the 1,3-diene, respectively. The reaction of (7)-1,3-dienes was then performed for comparison. 

These types of compounds can also be formed via a Wittig reaction [19]. Triphenylphosphine can be quatemized with a suitable alkyl iodide, and the resultant perfluoroalkylated phosphonium salt will react with aldehydes to give fluorinated alkenes which are easily hydrogenated (Scheme 3.4). This methodology has recently been expanded to the formation of perfluoroalkylated pyridines [20],... 

Historically, the concept of EG Bs was developed in relation to electrochemically induced Wittig reactions [45], Co-electrolysis of the phosphonium salt and the carbonyl compound was carried out using the carbonyl compound as the solvent and gave reasonable yields of the alkene [45]. Most of these reactions can be rationalized within Scheme 19, in which the phosphonium ion participates both as the probase (PB) and as the acidic substrate [46]. 

Yields of alkenes fi om the elecfrochemical Wittig reaction between phosphonium salt 19 and aldehydes from Ref. [87]. 

The Wittig reaction is one of the most important reactions in organic chemistry for synthesizing alkenes with unambiguous positioning of the double bond. The process involves a reaction between a phosphonium ylide and an aldehyde or ketone 150). The reacting ylide is formed from a phosphonium salt in a solution of a base such as NaH, t-BuOK, or NaOH 151) (Scheme 19). 

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

Two standard routes to y-functional phosphonium salts with electron-withdrawing groups consist in using the corresponding Michael alkenes to achieve either halide substitution in the -position to the functional group, in order to obtain y-functional vinylphosphonium salts, or Michael addition in the presence of acid to produce the y-functional alkylphosphonium salt (reaction 85). 

In another example710, the phosphonium salt 76 decomposes competitively by the two mechanisms of substitution and elimination (reaction 211). This salt behaves in a manner intermediate between salts 74 and 75 indeed, the SN(P) mechanism is not completely excluded as for the salt 74 but the EHfi mechanism is still favoured with regard to the salt 75 since the alkene formed is stabilized. 

The method of Kim et al.[89-93] starts from the synthesis of the three-carbon phosphonium salt according to the modified method of Corey et alJ94,95] The Wittig reaction of the phosphonium salt with a Z-protected a-amino aldehyde using potassium hexamethyldisilazanide provides the ds-alkene without racemization. Efficient hydrolysis of the orthoester without double bond migration is achieved by acidolytic hydrolysis with aqueous hydrochloric acid in tert-butyl alcohol under reflux conditions. Then, an a-amino acid methyl ester is coupled. The desired epoxide product is obtained by treatment with 3-chloroperoxybenzoic acid. The epoxidation reaction is stereoselective and predominantly provides one isomer (R,S S,R = 4-10 1). The trans-epoxide can also be prepared using a trans-alkene-containing peptide. A representative synthetic procedure to obtain the ds-epoxide isostere is detailed below. 

The method of greatest applicability is the reaction of alkali metal phosphides with dihalo-alkanes, -alkenes, etc. (equation 4). Generally this reaction proceeds well and in high yield excess dihaloalkane should be avoided as this leads to the production of phosphonium salts which can contaminate the product. 

The addition of ammonium and phosphonium salts as catalysts for HI addition to alkenes has been recommended as a useful alternative procedure.68... 

---