Reaction with Alkyl and Aryl Halides

In 1861 A.W. Hofmann isolated from the interaction of phosphorus with ethyl iodide and zinc in a sealed tube at 150 to 160 °C for several hours three products, e.g. 

Some years later, Carius found that ethyl iodide also alkylates white or red phosphorus in the absence of zinc when the mixture is heated in a sealed tube to 150 — 170 °C. The following equation was proposed  

Interest in the preparation of tertiary phosphine oxides by this route has recently been revived by several groups of workers with the result being considerable improvement in the synthesis of tertiary phosphine oxides by this method (Kirsanov and coworkers) (for a summary see Table 1). 

Thus heating red phosphorus and lower alkyl iodides (ratio 1.5 3) in the presence of a trace of iodine or diphosphorus tetraiodide in an autoclave at 200 °C for eight hours, followed by treatment with aqueous sodium sulfite or successive treatments with nitric acid and aqueous base gave Me3PO (54%), Et3P0 (56%) and BU3PO (66%) 

Alkylations of phosphorus with higher alkyl iodides, s,so) benzyl iodide, 

Halophosphines are produced by reactions of phosphorus with alkyl chlorides, alkyl bromides, or aryl bromides in solution (12) and by reaction of red phosphorus in tlie presence of copper with alkyl halides in tlie vapor phase (13). Both methods require temperatures in excess of 2 )0°. The preparation of halopliosphines in solution is illustrated by the results of uncatalyzed white phosphorus reactions summarized in Table I (12). Alkyl dihalopliosphiues are the predominant products under these conditions, but appreciable yields of dialkylmonohalophos-phines are also obtained. The reaction temperature requirement de- 

Uncatalyzed Reactions of Phosphorus with Orj anic Halides (12) RX -H — RPX, -I- R,PX 

RX Moles RX P4, gram atoni.s Temp., °C. Time. hr. Conversion, %  

Phos])horus modification Reactant ratio Phosphorus CF3I, g. at., moles Tern])., °C. Conversions based on CF3I, % Recovered CF3I, % Ref. 

Iodine (0.24 g. at. per gram atom of i)host)horus) was pre.sent. 

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For alkyl and aryl halides, the quenching rates with Pt2(pop)4 follow the sequence aryl iodide > alkyl halide, and Phi > PhBr > PhCl. The latter sequence parallels that of the relative ArX bond strengths. The first step in the reaction with alkyl and aryl halides is halogen atom abstraction by the A2ii state of Pt2(pop) to give Pt2(pop)4X" (Refs. 38 and 50) ... 

Organozinc compounds have been extremely useful reagents in the Negishi cross-coupling reactions with alkyl and aryl halides creating a new C—C bond (Scheme 13.28). The Negishi Ni, Pd, or Fe mediated cross-coupling reactions have proved to be powerful tools in vast areas of synthesis. 

Palladium(O) complexes undergo oxidative addition to form Pd11 dH complexes readily. They form hydrido, chloro or dichloro species with HC114,24,35 and also react with alkyl and aryl halides.36 52 These reactions are exemplified in Scheme 3. 

Atom-abstractive addition of Cpji YbOEt2 with alkyl and aryl halides give Cp YbX and Cp YbX2 where X = halide [149]. The side products of the reaction are Cp H, R-R, RH. 

There is presumably more than a subtle difference between the reactions of alkyl and aryl halides with organocopper compounds, as a straightforward nucleophilic displacement of aryl halide by the d electrons of a copper species is hardly likely. Simple aryl halides are nearly all inert to the usual nucleophiles, such as alkoxides, unless strongly activated by electron-attracting groups in the ortho and para positions. However, coordination of the halogen to copper may be sufficient to... 

Subsequent to his discovery that alkylaluminum compounds in conjunction with suitable alkyl halides are effective initiator systems for synthesizing high molecular weight polyisobutylene (/), Kennedy in 1970 (6) studied the reaction between alkyl and aryl halides with tri-methylaluminum using methyl chloride solvent at —78° C. The results... 

This method has also been quite useful for the synthesis of triorganoarsenic compounds. Arsenide anions, which can be prepared by several methods (vide infra), react with alkyl and aryl halides. Several examples are shown in equations 18 , 19 , 20 °, 21 , 22 23 , 24 and 25 . In the reaction with alkyl halides inversion of configuration at the sp carbon atom takes place and in the reaction of vinyl halides retention of configuration has been observed (equations 18 and 21). Photostimulated reaction with aryl halides has been reported to proceed via the Sjj l mechanism thus, the ketone group is compatible with the reaction conditions as shown in equation 23 . 

Reactions of Activated Magnesium with Alkyl and Aryl Halides... 

Once palladacycle formation has occurred, a number of possibilities exist for its reaction. A side product often seen in Catellani reactions is cyclobutane (21) formation resulting from a reductive elimination of the palladacycle (Scheme 7). In fact, under optimized conditions it is possible to achieve good yields of the cyclobutane products [26], However, the focus of this section will be to examine the reaction of the palladacycle with alkyl and aryl halides. 

There is little information on reactions of Be with alkyl and aryl halides ... 

Reaction of alkyl and aryl halides with salts and derivatives of hydrogen sulfide... 

The steroidal a-(isocyanomethyl)phosphonates (130) and (133) have been synthesized by methylation of the carbanions (129) and (132), respectively.66 Compounds (130) and (133) behave as N,P-ketals in that they can be hydrolysed to the corresponding ketones (131) and (134) (Scheme 10). A range of a-substituted a-aminophosphonic acids (136) have been prepared in moderate to excellent yield by the alkylation of the protected a-aminophosphonate (135) with alkyl and aryl halides and Michael acceptors under phase transfer catalysis (Scheme 11).67 The reactions of the lithium carbanion of diethyl prop-2-enyIphosphonate (137) with a,P-unsaturated ketones and esters have been investigated.6S Attack can be at the a- or y-positions in the phosphonate although in all cases Michael addition to the a, p-unsaturated carbonyl is preferred to attack at carbonyl carbon. In some examples simple adducts (138) are formed, but in more complex cases addition is followed by cyclisation to give (139) (Scheme 12). The bisphosphonate (141), which is a potent inhibitor of myo-inositol monophosphatase, has been prepared with the phosphonylation of the carbanion of (140) as a key step.6 9... 

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