Appel reaction

The reaction between triphenylphosphine and tetrahalomethane (CCI4, CBr4) forms a salt known as Appel s salt. Treatment of alcohols with Appel s salt gives rise to the corresponding halides. 

Example 2, Appel s salt is often used as a dehydrating agent 

Kleinstueck, R. Ziehn, K. D. Angew. Chem., Int. Ed. Engl. 1971, 10, 132. Rolf Appel was a professor at Anorganisch-Chemisches Institut der Universitat in Bonn, Germany. 

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The Appel reaction (between dialkyl hydrogen phosphate and amine... 

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

There are two processes called the Appel Reaction. Although similar, the second is concerned with reactions of phosphorous ... 

Halides are often prepared in a single step from alcohols through use of the Appel reaction. The reagents in this synthesis are tri-phenylphasphine and a halogen species such as tetrachloromethane, hexachloroacetone, or iodine. In place of the Appel reaction it is often possible to use inorganic acid chlorides, including phosphorus tribromide or thionyl chloride (see Chapter 16). 

Heterosubstitutions.—One of the most useful processes for conversion of alcohols into halides (mostly chlorides) is the Appel reaction.247 Treatment of free sucrose with Ph3P and CC14 in pyridine affords tiA -dichloro-b/i -dideoxysucrose in 91% yield.248,249 Surprisingly, a similar procedure performed on a penta-D-benzylsucrose was much less selective.250 Other dihalosucroses (bromides, iodides) are also accessible by reaction with modified Appel or related reagents.251,252... 

Dibromoalkenes (R R C = CBr2) have been prepared analogously by Appel reaction of the requisite ketone with carbon tetrabromide/triphenylphosphane. - ... 

The resulting propargylic alcohol is protected as TIPS ether by a standard procedure using the corresponding silyl chloride and imidazole in DMF. Optionally the more reactive silyl triflate and 2,6-lutidine may be employed in order to shorten the reaction time. Under acidic conditions TIPS and TPS are nearly stable protecting groups. Therefore the TBS ether is selectively cleaved with acetic acid even in presence of the acetal moiety. Subsequent reaction with iodine and triphenylphosphine, known as the Appel reaction, provides the desired iodide 4. 

Bis(hydroxymethyl)phosphonic acid esters that incorporated thymine were employed as a backbone to prepare short oligonucleotide chains. This chain was prepared by condensation of the bis(4,4 -dimethoxytrityl) protected phosphonic acid and iV or N -(2-hydroxyethyl)thymine in the presence of l-(2-mesitylenesul-fonyl)-3-nitro-l,2,4-triazole or by an Appel reaction with or N -(2-aminoethyl)thymine (89a-h). Selective removal of one DMT-group and phos-phitylation yielded the building blocks for solid supported synthesis of the short oligomers by the phosphoramidite approach. Holy has reported the synthesis of 8-amino and 8-substituted amino derivatives of acyclic purine nucleotide analogues. The 8-amino, 8-methylamino- and 8-dimethylamino-adenine and -guanine analogues of iV-(2-phosphonomethoxyethyl) and (S)-iV-(3-hydroxy-2-phosphono-methoxy-propyl) derivatives of purines (90a-i), were prepared by... 

In the second step, the resulting alcohol is transformed to an alkyl iodide via an Appel reaction. 

The next reaction in this sequence is an Appel reaction, which transforms an alcohol to an alkyl iodide. The simplified mechanism is depicted in the margin. The initial step of this reaction is the nucleophilic attack of triphenyl phosphine to iodine with formation of an iodine triphenyl phosphonium cation. The positive charge increases the oxophilicity of phosphorus, which is attacked in the next step by an alcohol. After elimination of hydrogen iodide, the resulting alkoxy triphenyl phosphonium cation is attacked by an iodide anion in an SN2-type reaction. Therefore, the reaction of chiral alcohols typically proceeds with inversion of configuration, although other behavior is also reported. The product of the Appel reaction is alkyl iodide 37 and triphenyl phosphine oxide is formed as byproduct. ... 

The first transformation is an Appel reaction the mechanism is shown below. The carbanion 55, which is generated in situ from PR3 and... 

Another example of the transposition of the C2-C3 double bond into the C3-C4 position was reported by Lubineau [46]. Tri-O-acetyl-D-glucal 23 was converted in three standard steps into 2,3-unsaturated sugar 41. The modified Appel reaction provided bromide 42 which reacted with aldehyde in the presence of metallic indium affording the 3,4-unsaturated product 43 (O Scheme 22). 

The preparation of (Rp) and (Sp)-N, N, O -tribenzoyladenosine 3, 5 -phosphoranilidates (96) has been greatly improved by treating the cyclic phosphate (97) with oxalyl chloride and a catalytic amount of DMF, rather than the triphenylphosphine-carbon tetrachloride mixture (Appel reaction) used previously, followed by addition of aniline. 5 near-quantitative yield of (97) obtained as a mixture of diastereoisomers is easily separated. The cyclic phosphoramidates (98-100) have also been obtained in improved yield by treating cAMP with a mixture of phosphoryl chloride and trimethyl phosphate (which had previously been pretreated with one-half a molar equivalent of water) at 0°, followed by ammonium carbonate or the appropriate amine. x e (Sp)-diastereoisomers are formed in excess, e.g. for (100) yields of 13 % of the Rp-isomer and 54 % of the Sp-isomer are obtained, and the proportion of Rp-product decreases further if pre-treatment with... 

This reaction was first reported in 1966 by Lee et al., after the initial work of Horner et al. for the halogenation of alcohol using triarylphosphine dihalides in 1959. In this reaction, primary and secondary alcohols are transformed into corresponding chlorides with a remarkable tendency of inversion of the configuration when the alcohols react with triphenylphos-phine and carbon tetrachloride. This reaction has been extensively reviewed by Appel and is generally known as the Appel reaction. Likewise, the mixture of triphenylphosphine and carbon tetrachloride is referred to as the Appel reagent and Appel agent. ... 

This reaction is related to the Appel Reaction, Staudinger Reaction, and Michaelis-Arhuzov Rearrangement. 

GiUieany et al. [71-76] reported the oxidation of tertiary phosphine 133 with polyhaloalkanes in the presence of chiral proton-donating auxiliary L-menthol (the asymmetric Appel reaction). As a result, chiral phosphine oxides 134 were prepared with good enantiomeric excess. The latter were then treated with LDA and copper chloride to afford the bis-phosphine oxide which is a useful chiral ligand for asymmetric catalysis. The chiral bis-phosphine oxide R,R)-liS was produced in 98% ee and the minor amount of meso-isomer formed was easily removed by recrystallization from benzene, which yielded enantiopure (>99.9% ee) bis-phosphine oxide 135 in an isolated yield of 73% from the racemic phosphine 133 (Scheme 41). 

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