Arbuzov reaction, aryl halides

ARBUZOV MICHAELIS Phosphonale Synihesis Ni catalyzed phosphonate synthesis from phosphites and aryl halides Reaction of alkyl halides with phosphites proceeds without nickel salts... 

The earliest developments in transition metal-assisted formation of aromatic C-P linkages were the result of the efforts of Tavs28 that were concerned with the use of Ni(II) halide salts for the reaction of aryl halides with trialkyl phosphites. These reactions involved conditions reminiscent of the Michaelis-Arbuzov reaction (heating at an elevated temperature) and produced arylphosphonate products in reasonable yield (Figure 6.8). 

Allyl and propargyl halides participate in the Michaelis-Arbuzov reaction, though isomerization is sometimes observed. The Michaelis-Arbuzov reaction of alkynyl halides (15, Scheme 8) is synthetically useful when the alkyne is suitably substituted (e.g. Scheme 8, R2 = aryl, substituted ethenyl, Me3Si, Et3Sn, Cl, X = Cl, Br) and the area has been reviewed.37... 

Vinylphosphonates are useful reagents but simple vinyl halides do not undergo the Michaelis-Arbuzov reaction except in the presence of a transition metal catalyst [Ni(II) or Cu(I), cf. Protocol 4] so vinylphosphonates are usually synthesized from other functionalized phosphonates or by the palladium-catalysed Michaelis-Becker reaction (cf. Protocol 8).38 Similarly, simple aryl halides undergo the Michaelis-Arbuzov reaction only under special conditions palladium or nickel species (Protocol 4) are suitable catalysts. Indeed these and other catalysts have been applied to the Michaelis-Arbuzov reaction of various substrates, though they are generally essential only with vinyl and aryl halides, as described herein.39... 

Apart from their behaviour as ligands in metal catalyst systems, studies of the reactivity of phosphites towards a wide variety of other substrates have attracted attention. New aspects and applications of the classical Michaelis-Arbuzov reaction and its variants continue to appear. Evidence of the thermal disproportionation of methyltriaryloxyphosphonium halides formed in the reactions of triarylphosphites with alkyl halides, together with the formation of P-O-P intermediates, has been reported. The Michaelis-Arbuzov reaction has been used in the synthesis of phosphonate-based styrene-divinylbenzene resins and polyphosphonated chelation therapy ligands.Treatment of electron-rich benzylic alcohols dissolved in triethylphosphite with one equivalent of iodine affords a low-temperature one-pot route to the related benzylic phosphonates, compounds which are otherwise difficult to prepare. Upper-rim chloromethylated thiacalix[4]arenes have also been shown to undergo phosphonation on treatment with a phosphite ester in chloroform at room temperature. The nickel(II)-catalysed reaction of aryl halides with phosphite esters in high boiling solvents, e.g., diphenyl ether, (the Tavs reaction), has also... 

There are three main decomposition pathways for 7 elimination of (i) RX, (ii) R X or (iii) R"CHO shown in Scheme 8. The route via (i) has been termed a retro-Arbuzov reaction. The decomposition pathway is structure-sensitive, route (i) being characteristic for R = alkyl. When R = aryl, route (ii) is favoured especially if the volatile halide is... 

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... 

Sentemov, V.V., Krasil nikova, E.A., and Berdnik, I.V., Mechanism of the catalysis of the Arbuzov reaction by complex compounds of transition metals. Part 3. Influence of the nature of the aryl halide used on the ease of Arbuzov reaction catalyzed by metal complexes, Zh. Obshch. Khim.. 59, 2692, 1989 J. Gen. Chem. USSR (Engl. Transl.), 59, 2406, 1989. 

One might expect that a phosphorus reagent having for R an aryl group activated for bimolecular nucleophilic substitution (68) by electron- withdrawing substituents might participate in a Michaelis-Arbuzov reaction. Kamai and Koshkina (159), who prepared a number of chloro-and nitro-substituted derivatives of triphenyl phosphite, found this to be the case for both ortho and para isomers of tris(monochlorophenyl) phosphite, which reacted with alkyl halides to furnish phosphonates. On the other hand, tris(2,4,6-trichlorophenyl) phosphite and tris(2,4-dichlorophenyl) phosphite (155) gave only complexes with methyl iodide however, lower reaction temperatures were employed. 

Aminophosphines, phosphinites and phosphonites from quasi-phosphonium salts with alkyl halides in normal 5 n reactions. The aminophosphonium salts and the salts derived from aryl phosphinites and diaryl phosphonites are stable, but the majority of the quasi-phosphonium salts which contain alkoxy groups are dealkylated during the reaction with the alkyl halide (the Arbuzov reaction, see below). Thio analogues of phosphinites and... 

Representative examples of Arbuzov reactions with alkyl phosphinites and phos-phonites are the preparation of some bisphosphinates (equation 122) functionalized trialkylphosphine oxides (equation 123) and phosphorylated sarcosine analogues (equation 124). Examples involving aryl halides (equation 125) ", a vinyl halide (equation 126) , an alkynyl halide (equation 127) and an acyl halide (equation 128) illustrate the diversity of the reaction. Arbuzov reactions that involve trimethylsilyl phosphinites or phosphonites occur under very mild conditions, usually at or below room temperature, e.g. equation 129 ... 

Coordinated phosphites may also be modified by metal catalysis to act as nucleophiles. For example, in the nickel-catalyzed Arbuzov reaction [110, 111], after oxidative addition of an aryl halide, attack of free or metal-bound halide at... 

Scheme 62 Proposed mechanism of cross-coupling in a nickel-catalyzed Arbuzov reaction of aryl halides...

Keywords Arylmethyl and heteroarylmethyl halides/alcohols, zinc bromide, dichloromethane, room temperature, Michaelis-Arbuzov reaction, arylmethyl and heteroarylmethyl phosphonate esters, aryl aldehydes, diethyl [hydroxyl(arylmethyl)]phosphonate... 

The P-arylation of arynes is an interesting approach to the synthesis of arylphosphine oxides since it is typically a transition metal-free reaction that occurs at low temperatures (Scheme 4.193) [332]. In contrast to classic metal-mediated Arbuzov-type reactions between phosphinites and aryl halides that required high temperatures (150-2(X) °C), this... 

A facile preparation of aryl or heteroaryl substituted methylphosphonate esters (470) in good yields, involving a Lewis acid mediated Michaelis-Arbuzov reaction of arylmethyl halides/alcohols (468) with triethyl phosphite (469) at room temperature, has been described by Mohanakrishnan et al. (Scheme 116). ... 

Arbuzov and Michaelis-Becker reactions provide facile and versatile procedures for the formation of carbon-phosphorus bonds. These methods, however, are not applicable to the formation of sp hybridized carbon-phosphorus bonds. Only few methods have been reported for the syntheses of arylphosphonates and vinylphospho-nates. Direct reaction of aryl or vinyl halides with trialkyl phosphite in the presence of nickel halide requires severe reaction conditions [21,22], and the stereochemistry of vinylphosphonates has not been clarified. Synthesis of dialkyl arylphosphonates 22 [23, 24] is achieved by the palladium-catalyzed reaction (Scheme 2.12), which is called by Hirao reaction . The stereoselective synthesis of dialkyl vinylphosphonates 23 [24-26] is similarly accomplished by this method (Scheme 2.13). A variety of modified procedures have been developed recently [27-37]. 

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