Michaelis-Arbuzov reaction mechanism

Trialkyl phosphites undergo reaction with molecular halogen via a mechanism reminiscent of the Michaelis-Arbuzov reaction to form the dialkyl phosphorochloridate in good yield (Equation 4.4).7 With cyclic esters, the halogen performing the displacement reaction at carbon remains attached within the molecule. 

The formation of an s/Z-hybridized C—P bond is readily achievable using the Michaelis-Arbuzov reaction. Such an approach is not applicable to form heteroaryl C—P bonds in which the carbon atoms are sp2 hybridized, whereas palladium catalysis does provide a useful method for Csp2—P bond formation. The first report on Pd-catalyzed C—P bond formation was revealed by Hirao et al. [134-136]. Xu s group further expanded the scope of these reactions [137, 138], They coupled 2-bromothiophene with n-butyl benzenephosphite to form n-butyl arylphosphinate 161 [137]. In addition, the coupling of 2-bromothiophene and an alkylarylphosphinate was also successful [138], For the mechanism, see page 19-21. 

To gain information on the kinetics and mechanism of the product-forming stage of the Michaelis-Arbuzov reaction, we have followed the decomposition of intermediates by H nmr spectroscopy. In CDCI3 the reactions follow excellent first-order kinetics (Table I) and are in accord with rate-determining collapse to products within the undissociated ion-pair (Figure 1). Synchronous... 

Clemens, J., Neukomm, H., Werner, H. Reactivity of metal rt-complexes. 14. Preparation and formation mechanisms of rc-cyclopentadienylnickel (tert-phosphite) dialkylphosphonate complexes, an organometallic variant of the Michaelis-Arbuzov reaction. Helv. Chim. Acta 1974, 57, 2000-2010. 

Hudson, H. R., Kow, A., Roberts, J. C. Quasiphosphonium intermediates. Part 3. Preparation, structure, and reactivity of alkoxyphosphonium halides in the reactions of neopentyl diphenylphosphinite, dineopentyl phenylphosphonite, and trineopentyl phosphite with halomethanes and the effect of phenoxy-substituents on the mechanism of alkyl-oxygen fission in Michaelis-Arbuzov reactions. J. Chem. Soc., Perkin Trans. 2 1983, 1363-1368. 

In view of the supposed inertness of halo-unsaturated substrates in the Michaelis-Arbuzov reaction, it is remarkable that arylalkynyl halides are more reactive than comparable alkyl, aryl, or vinyl halides toward trialkyl phosphites. The success of the Michaelis-Arbuzov reaction in the synthesis of dialkyl 1-alkynylphosphonates from 1-haloaIkynes has provoked a number of mechanistic studies. Three sites, the halogen, oc-carbon, and P-carbon have been investigated as the zone of the initial nucleophilic attack by trialkyl phosphites. Studies to date suggest that the reaction proceeds by at least two different mechanisms, and that probably the most important of these involves positive halogen-abstraction (path a) as outlined in Scheme... 

In contrast to the Michaelis-Arbuzov reaction, which is carried out by heating the reactants together at 120-160° for several hours, the Mi-chaelis-Becker-Nylen reaction often takes place at room temperature, particularly when tetrahydrofuran is employed as the solvent (128). The temperature advantage is frequently offset by the greater tendency of the ionic phosphorus reagents to participate in side reactions. The mechanism of the Michaelis-Becker-Nylen reaction, often assumed to be SN2, is not established with certainty (283). 

Adequate understanding of the mechanism of the Michaelis-Arbuzov reaction has been hampered by a deficiency of thorough kinetic investigation. On the basis of specific volume measurements, Zawidski and Staronka (303) in 1915, and Staronka (291) in 1927, proposed an empirical rate equation to correlate their data. This equation in modified form (eq. 5) has more recently been applied by Isbell and associates... 

The relative ease with which triarylmethyl halides enter into the Michaelis-Arbuzov reaction is also suggestive of an SNl mechanism, although a homolytic process has been proposed (22). 

A simple and efficient route to a variety of structures containing phosphorus-carbon bonds, under mild conditions and in good chemical yields, has been developed by Michalski and co-workers. Halotrimethylsilanes MesSiX (X = Br, I) catalyzed rearrangements of tricoordinate phosphorus esters (584) into the corresponding phosphoryl systems (585) (Scheme 144). Experimental evidence indicated that the mechanisms of the reactions were fundamentally different from that of the Michaelis-Arbuzov reaction. 

First assumptions about the mechanism were based on an ordinary Michaelis-Arbuzov reaction (Scheme 2.107, Path A), [139], which includes protonation of the phosphorus atom followed by nucleophilic substitution of one methyl group [140]. 

Evidence has been presented for ionic intermediates of formula Mo(A5-C5H6)(CO)2[P(OR)3]2 + Mo(A -C5H5)(CO)3 - in the reaction of the dimer [Mo(A -C5H5)(CO)3]2 with phosphites. The mechanism closely resembles that of the Michaelis-Arbuzov reaction of alkyl halides with... 

Group VII. The rate law for reaction of PhaM—Mn(C0)6, where M = Si, Ge, or Sn, with a variety of nitrogen and phosphorus bases, both unidentate (e.g. phosphines) and bidentate (e.g. diphos, bipy), indicates parallel dissociative and associative mechanisms in all cases. This assignment of mechanisms on the basis of the rate law is supported by activation entropies determined for the respective terms. Exceptionally, the reaction of PhaSi—Mn(CO)s with trialkyl phosphites does not result in simple substitution of carbon monoxide by the phosphite, but produces trans-Mn(COR)(CO)s[P(OR)3]2 by way of a Michaelis-Arbuzov reaction. ... 

The use of an electron-rich trivalent phosphorus center for addition to or substitution at an electrophilic site is a long-established approach to the formation of carbon-phosphorus bonds. The classical studies of the Michaelis-Arbuzov, Michaelis-Becker, Abramov, Pudovik, and related reactions and their mechanisms and synthetic utilities have been thoroughly reviewed. In this chapter, we present only a brief introduction to these reactions and provide several examples of their more facile uses from the older literature. More attention is given to relatively recent developments regarding such reactions that are seen as improvements in their general utility. 

Classical Michaelis-Arbuzov or Michaelis-Becker approaches toward formation of C-P bonds involving aromatic carbon sites are (understandably) not generally feasible. Nucleophilic substitution reactions on aromatic carbon proceed only under particular circumstances relating to the nature of attendant additional substituents, and then often with mechanisms quite different from those observed in... 

This protocol is essentially Tavs method40 as reinvestigated by Balthazor and Grabiak.41 Anhydrous nickel(ll) chloride or bromide (5 mol%) may be used as the precatalyst and is reduced by triethyl phosphite to tetrakis(triethyl phos-phite)nickel(O) (which may be prepared separately and used as the catalyst in the Michaelis-Arbuzov step).41 The mechanism of the reaction has been... 

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). 

The reaction of trialkyl phosphites with perfluoroalkenes in an autoclave at l(X)-140°C results in the formation of dialkyl perfluoroalkenylphosphonates in low to good yields (21-81%, Scheme 3.7). " The mechanism involves the attack of the phosphite nucleophile at the polarized terminal CF2 position to form a perfluoroalkenyltrialkoxyfluorophosphorane, which is stable under the usual conditions. This fluorophosphorane, which may be regarded as an isolable Michaelis-Arbuzov intermediate, decomposes on heating with elimination of alkyl fluoride to give dialkyl perfluoroalkenylphosphonates (Scheme 3.7). ... 

The reaction between trialkyl phosphites and a,P-unsaturated nitriles has been less thoroughly investigated. Whereas the hydrophosphonylation of unsaturated nitriles with diakyl phosphites proceeds smoothly, the addition of trialkyl phosphites requires more severe conditions. It involves the nucleophilic attack by the trivalent phosphorus reagent at the tenninal carbon atom of the conjugated system followed by valency expansion of phosphorus in agreement with the Michaelis-Arbuzov mechanism (Scheme 6.27). - ... 

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. 

Phosphorus. Reactions of three-co-ordinate phosphorus(m) compounds generally involve associative mechanisms, as in exchange at (Me2As)2P(CF3), in the reaction of phosphines with hydroxide, and of trialkyl phosphites with hypochlorite. In the last case, the phosphorus appears to be five-co-ordinate in the transition state. The reaction sequence for trialkyl phosphites plus phosphorus trifluoride includes a Michaelis-Arbuzov rearrangement. The first stereochemical study of reactions of phosphorus(iii) compounds with radicals demonstrates retention of configuration this result is consistent with more than one possible mode of reaction. Further examples of reactions of phosphorus(iii) compounds appear later, when analogous derivatives of phosphorus(m) and phos-phorus(v) are compared. 

Fundamentally, the Michaelis-Becker reaction, and the first step in the mechanism of the Arbuzov reaction, involves 8 2 substitution at the carbon atom and as such should lead to stereospecific formation of the C—P bond (with inversion of configuration at the carbon atom) when chiral alkyl halides are used. Secondary alkyl halides, in most cases, favor elimination instead of substitution, in contrast to epoxides that react with phosphorus nucleophiles without elimination and with excellent stereoselectivity. The later reaction was successfiiUy used in a synthesis of glycosylphosphonate analog 3 of T>-myo-inositol-1,4,5-triphosphate (Scheme 47.2). ... 

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