Phosphines nucleophile oxidation

The phospha-Michael reaction has been the last hetero-Michael reaction to be developed under iminium activation. In addition to the selectivity issues that have to be addressed, the identification of a suitable phosphorous nucleophile has been the most difficult task to overcome when developing the reaction because of the high tendency of phosphines toward oxidation in the presence of air. The first example was developed independently by Melchiorre and... 

Lewis base or nucleophilic catalysis by chiral amines, amine or phosphine iV-oxides, sulfides, and phosphines has been intensively exploited in asymmetric organocatalysis [122]. Representative catalysts are shown in Figure 2.27. 

A catalytic system amenable to nucleophilic oxidations uses tri-fluoromethyl hydroxy palladium or platinum bis-phosphine complexes [81]. This has been extensively studied in the laboratory but not yet used industrially. 

Oxidation of free phosphines was mentioned above as a reaction leading to phosphine loss. Here we will discuss three further ways of phosphine decomposition oxidative addition of phosphines to low-valent metal complexes, nucleophilic attack on coordinated phosphines, and aryl exchange via phosphonium species. Interestingly in all cases the metal serves as the catalyst for the decomposition reaction ... 

Another very important reaction initially involving nucleophilic attack on an aldehyde carbonyl is the Wittig reaction. An yUd adds to the carbonyl forming a betaine intermediate which then decomposes to produce an olefin and a tertiary phosphine oxide. 

Preparation and Properties of Organophosphines. AUphatic phosphines can be gases, volatile Hquids, or oils. Aromatic phosphines frequentiy are crystalline, although many are oils. Some physical properties are Hsted in Table 14. The most characteristic chemical properties of phosphines include their susceptabiUty to oxidation and their nucleophilicity. The most common derivatives of the phosphines include halophosphines, phosphine oxides, metal complexes of phosphines, and phosphonium salts. Phosphines are also raw materials in the preparation of derivatives, ie, derivatives of the isomers phosphinic acid, HP(OH)2, and phosphonous acid, H2P(=0)0H. 

Because of their relative instabiUty, primary phosphine oxides caimot be isolated and must be converted direcdy to derivatives. Primary and secondary phosphine oxides undergo reactions characteristic of the presence of P—H bonds, eg, the base-cataly2ed nucleophilic addition to unsaturated compounds such as olefins, ketones, and isocyanates (95). 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

Recently, Fossum et al. prepared several phosphine-oxide-containing monomers (Scheme 6.23).163 These monomers were used to prepare hyperbranched polymers in a typical aromatic nucleophilic substitution. However, only oligomers with M lower than 2500 g/mol were obtained. These results did not surprise us, since our previous work demonstrated that the para-hydroxyl group of the phosphonyl group is not very reactive and would require higher reaction temperatures.11... 

Hexa-fluorobisphenol A (HFBPA) based polysulfone and poly(arylene ether phosphine oxide) were prepared by nucleophilic aromatic substitution similar to that of bisphenol-A-based polysulfone and poly(arylene ether phosphine oxide).11... 

C. Nucleophilic Attack on Other Atoms.—Amidoximes have been shown to react with tris(dimethylamino)phosphine by displacing dimethylamine to give the phosphine oxides (52), but some N-substituted aromatic amidoximes give derivatives of (53). ... 

A. Nucleophilic Reactions of the P=0 Group.—Tris(trifluoromethyl)-phosphine oxide (33) reacts with hexamethyldisiloxane to give a phos-phorane, whose n.m.r. spectrum at — 140 °C shows non-equivalent trifluoromethyl groups. Although this unusual reaction clearly involves nucleophilic attack of the phosphoryl oxygen on silicon at some stage of the reaction, a full study of the mechanism has not been published. Tertiary phosphine oxides can be converted cleanly into dichlorophos-phoranes (34) by treatment with two moles of phosphorus pentachloride. Alkylation of the sodium salt of tetraphenylmethylenediphosphine dioxide (35) with alkyl halides, in dimethyl sulphoxide, has been reported to... 

The different products obtained from the analogous reaction of diphenyl-phosphine oxide are explained in terms of the hardness of nucleophilic centres involved. Similar reactions with 2-methyl-3,4,5-triphenylcyclo-pentadienone gave the phosphonate (39). Gallagher and Jenkins have... 

This reaction may be visualized as proceeding by nucleophilic attack of tervalent phosphorus at the carbonyl group to give an intermediate such as (15). The structure of (16) was deduced from the fact that it was hydrolysed to the known phosphine oxide (17). Methylenephosphoranes (phosphorus ylides) may also be converted into monophosphazenes by reaction with benzonitrile ... 

The relatively basic (hydroxyalkyl)phosphines act toward LMCs as reductants and, compatible with this, also as strong nucleophiles. We have studied such reactions in aqueous and D2O solutions by P-, H-, and C-NMR spectroscopies (including 2D correlation methods), product isolation and, when possible, X-ray analysis of isolated compounds or their derivatives. Thus, aromatic aldehyde moieties present in lignin (e.g., 3) are reduced to the corresponding alcohols (see 4) with co-production of the phosphine oxide in D2O, -CH(D)OD is formed selectively (36). The mechanism proceeds via a phosphonium species formed by initial nucleophilic attack of the P-atom at the carbonyl C-atom, i.e., via ArCH(OH)P%, where Ar is the aromatic residue and R is the hydroxyalkyl substituent (36). When the aldehyde contains a 4-OH substituent, the alcohol product... 

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... 

In contrast to the situation on flash pyrolysis, methyleneoxophosphoranes generated by thermolysis or photolysis in the presence of protic nucleophiles can be directly trapped to form corresponding derivatives of phosphinic acid (17- 19) however, the possibility of competing insertion of carbenes into the H/X bond of the additives is always present, giving phosphine oxides with X in the a-position (16- 18). Reaction branching at the carbene 16 was first observed on photolysis of 7 in water 13) and prompted detailed investigations on the phosphorylcarbene/ methyleneoxophosphorane rearrangement. 

A similar reaction sequence of triisopropylphenylphosphole or mesitylphosphole (17b and 17a, respectively) with phosphorus tribromide afforded the corresponding 2-substituted products. The reaction of dibromophosphine 37 with nucleophiles followed by oxidation or hydrolysis gave phosphonic or //-phosphinic derivatives (39 or 41, respectively) (Scheme 9) [48, 49], The regioselectivity is obviously the consequence of the presence or the lack of the steric hindrance with ortho tert-butyl groups, only position 3 is available, while with the smaller triisopropyl substituent, position 2 may be the appropriate reaction site. 

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

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