Phosphine oxide, from alkene

However, during the addition of -keto esters onto enals, ytterbium triflate proved to be an efficient catalyst [171] as in the Michael additions of a-nitro esters [172]. Several water-soluble phosphines gave the corresponding phos-phonium salts in good yields when added to a,j9-unsaturated acids [173] or activated alkynes [174]. With alkynes, vinyl phosphine oxides or alkenes were formed depending on the pH of the aqueous solution. Significantly, the reaction of nitroalkanes with buten-2-one is considerably accelerated when going from... 

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. 

Carbanions derived from phosphine oxides also add to carbonyl compounds. The adducts are stable but undergo elimination to form alkene on heating with a base such as sodium hydride. This reaction is known as the Horner-Wittig reaction.268... 

The lluorous biphasic technique has also been applied to the Wittig reaction, one of the most effective methodologies for the production of C=C double bonds [13] (Scheme 10.11). One of the major drawbacks of this reaction is the separation of the alkene from the phosphine oxide by-product. This is commonly achieved via recrystallization or column chromatography, but recently it has been shown... 

A large number of Group VIII metal-dioxygen complexes catalyze the oxidation of phosphine to phosphine oxide or isocyanides to isocyanates by molecular oxygen.6,12,56,140,141 146,184 However, their use as catalysts for the oxidation of alkenes generally leads to the same products as those obtained from free radical chain autoxidations.184,196-198... 

Another argument against the oxo-transfer mechanism in our catalytic aerobic oxidation protocol is the lack of formation of sulfoxides from sulfides, N-oxydes from amines and phosphine oxydes from phosphines. Alkenes also proved to be inert towards oxidation no epoxide formation could be detected under our reaction conditions. 

Thefcphosphine oxide can be reduced back to the phosphine (for example, with Cl- SiH) while still bound to the polymer and the polymer-bound reagent can be used again. Separation of Ph3P=0 from alkene products after a Wittig reaction can be quite a nuisance so the ease of work-up alone makes this an attractive procedure. 

Unlike the carbanions derived from phosphonate esters, the carbanions of dimethyl methylphosphonate18 and, in some instances phosphine oxides (Homer-Wittig reaction), do not react directly with aldehydes and ketones to give the corresponding alkene.2,3 Rather, the reaction yields an intermediate P-hydroxy derivative that can be isolated and purified to high diastereoisomeric purity. Subsequent reaction then gives the desired alkene with control of stereochemistry (see Schemes 3, 5 and Protocols 7, 8). 

Low reactivity of ot,(B-unsaturated ketones and sterically hindered ketones as well as separation of reaction products from phosphine oxide are a few disadvantages of the classical Wittig reaction. Phosphonate anions are stronger nucleophiles than related phosphoranes thus, alkenate hindered ketones under mild conditions. The dialkylphosphate (R2PO4), the other product of the HWE reaction, can easily be removed from the reaction mixture because it is soluble in water. 

Cyclopentadienyl complexes of cobalt exist mainly in three oxidation states Co Co, and Co. Co is represented by complexes of the type CpCoL2, where L is CO, alkene, alkyne, or phosphine. Apart from derivatives of cobaltocene, half-sandwich complexes (see Half-sandwich Complexes) (CpCoX)2 or CpCoLX with cobalt in oxidation state II are known. CpCo occurs in various CpCoL Xm compositions (Section 9.2). 

One of the main drawbacks of the Wittig reaction is the formation of unwanted triphenylphosphine oxide. A new route, which makes use of polymer-supported triphenylphosphine and microwave dielectric heating has been developed (Scheme 13), which yields the required alkene without the triphenylphosphine oxide. An alternative strategy for separation of the product alkene from unwanted phosphine oxide by-product is to carry out the Wittig reaction in a fluorous solvent using a perfluorinated ylide such as (45). One drawback of this... 

The use of anions derived from a phosphine oxide (132) or a diethyl phosphonate (133) to form al-kenes was originally described by Homer.Although these papers laid the foundations for the use of phosphoryl-stabiliz carbanions for alkene synthesis, it was not until Wadsworth and Emmons published a more detailed account of the general applicability of the reaction that phosphonates bet e widely used. Since the work of Wadsworth and Emmons was significant and crucial to the acceptance of this methodology, the reaction of a phosphonate caibanion with a carbonyl derivative to form an alkene is referred to as a Homer-Wadsworth-Emmons reaction (abbreviated HWE). The phosphine oxide variation of the Wittig alkenation is called the Homer reaction. 

Most recently, the immunosuppressive agent FK-S06 (416) has been the target of total synthesis. To date several approaches to the trisubstituted alkene region at C-19 and C-20 have appeared. These preliminary studies allow the comparison between the Warren phosphine oxide approach and the Julia coupling. In the first total synthesis of FK-S06, Jones and coworkers at Merck formed the the alkene deprotonadon of the phosphine oxide (418) and condensation with the aldehyde (417). The hydroxy-phosphine oxides were formed in a ratio of 1 1 in 77% yield. The less polar diastereomer was treat with base to obtain the ( )-alkene (419) in 32% overall yield from the aldehyde (equation 96). Danishefsky utilized the Julia coupling for the formation of the trisubstituted alkene region. The sulfone anion (420) was treated with isobu raldehyde as a model, followed by acetylation and reductive elimination to... 

In a more direct comparison of the phosphine oxide elimination with the sulfone, Schreiber employed a identical system to Danishefsky, but used the phosphine oxide (422). Reaction with isobutyralde-hyde and subsequent elimination resulted in a 1 1 mixture of the ( )- and (Z)-alkenes (421 equation 98). It appears from the more complex example of the Merck synthesis and from this example, that the Julia coupling proceeds with higher ( )-selectivity, in similar yield. 

Another variation of the Wittig reaction is the Wittig-Horner reaction, in which the anion generated ot- to phosphine oxide is used as a nucleophile to react with carbonyl compounds. The intermediate formed in this reaction, -hydroxyphosphine oxide, is isolable particularly when bases with lithium counterion are used for deprotonation. Since the j6-hydroxyphosphine oxides are diastereomers, they can be separated and subjected to elimination to form the corresponding alkenes. Since the elimination of phosphonate moiety is syn, stereospecific alkenes are obtained from the elimination step. As expected, the generation of erythro and threo isomers is dependent on the solvent and the reaction conditions. 

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