Arbuzov-Michaelis rearrangement intermediates

Brief consideration will be given to NMR investigation of intermediates, products and kinetics of reactions. Alkylation, arylation, metalation, reaction with organometallics, thermolysis and thermal rearrangements, isomerisation and many other reactions such as the Wittig, Michaelis and Arbuzov reactions, which are typical of organophosphorus... 

The possibility that R-0 fission may occur in advance of attack by halide ion has been demonstrated in the reactions of dineopentyl phenyl phosphite or neopentyl diphenyl phosphite with alkyl halides. In these cases the Michaelis-Arbuzov intermediates cannot be isolated but the neopentyl halides which are formed are contaminated with varying amounts of rearrangement product (t-pentyl halide) (Table IV). These results may explain the formation of mixtures of isomeric halides (9,10,11) in certain applications of Rydon s method for alkyl halide preparation (12). S i fission of the R-0 bond appears to be encouraged by the electron-attracting effect of phenoxy-substituents (Figure 3). 

The mechanism of the Perkow reaction has been a subject of some debate but is now generally thought to proceed by initial attack of phosphorus at the carbonyl carbon atom, not by rearrangement of a Michaelis-Arbuzov intermediate 5.77,78... 

The reaction is presumed to occur by initial formation of HjfMenO) PO], which then undergoes direct P-alkylation by nucleophilic attack of phosphorus on carbon with displacement of halide. An alternative alkylation mechanism involving nucleophilic attack of oxygen on carbon, followed by a Michaelis-Arbuzov rearrangement i) of a dialkyl phenylphosphonite (C6H5(MenO)POR) intermediate with the alkyl halide was effectively eliminated by the observation that reaction of methyl phenylphosphinate with a tenfold excess of methyl-c/3 iodide gave the product distribution shown in Eq. (2). 

Analogously, ethyl 4-fluoro-3-methylcrotonate is brominated with NBS in the presence of AIBN and then reacted with triethyl phosphite to produce good yields (72-78%) of a-fluorophosphonate, a key intermediate in the synthesis of fluorinated vitamin A esters (Scheme 3.3)7 Following a similar procedure (radical bromination and Michaelis-Arbuzov rearrangement), ( )-l-fluoro-3-(l-trityl-l,2,4-triazol-3-yl)-2-propenylphosphonate, a good inhibitor of imidazoleglycerol phosphate dehydratase, has been prepared in 25% overall yield. ... 

Many different mechanisms have been proposed for the Perkow reaction.2-4 It involves nucleophilic attack of the phosphite at the carbonyl carbon and affords a zwitterionic intermediate 5 which rearranges to form a cationic species 6 that subsequently dealkylates to give the corresponding vinyl phosphate 7. The conversion proceeds via a Michaelis-Arbuzov cleavage of an alkoxy group by halide ion as shown. 

Following a comparison of the behaviours of trialkyl phosphites, mixed alkyl phenyl phosphites and triphenyl phosphite towards iodomethane and, in the last case, the breakdown of the phosphonium salt when treated with an alcohol, Landauer and Rydon considered that all the reactions involve a stage identical with that of the normal Michaelis-Arbuzov reaction. The absence of any rearrangement during the decomposition of complexes from neopentyl phosphites, and the configurational inversion which occurs when optically active 2-halooctanes are produced from optically active phosphite triesters (themselves obtained from optically active octan-2-ol), suggest that the mode of breakdown of the intermediate complexes is of S 2 character. 

These polymerizations proceed mostly by a Michaelis-Arbuzov (M-A) type of rearrangement (Scheme 1), involving cyclic phosphonium intermediates to produce poly-phosphinates or polyphosphonates (39). The presence of isomerized repeating units (40) was the result of the occurrence of side reactions. Sometimes the proportion of the isomerized units was higher than that of the normal units (39). ... 

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