Triethyl phosphite, alkyl phosphonate from

Nucleophilic Reactions.—Attack on Saturated Carbon. Selected examples of the Arbusov reaction include phosphorylation of the chloroacetophenones (1) to give phosphonates, which cyclized to (2) in the presence of acid chlorides,1 formation of the azodiphosphonate (3) from 2,2 -dichloro-2,2 -azopropane,2 3 and the reaction of 2-chloro-3,4-dihydro-3-oxo-2//-l,4-benzothiazine (4) with triethyl phosphite to give the 2-phosphonate (5), which is used as an olefin synthon.8 Bis(trimethylsilyl) trimethylsiloxymethylphosphonite (6) has been synthesized by silylation of hydroxy-methylphosphonous acid, and, as expected, undergoes a normal Arbusov reaction with alkyl halides to give the phosphonates (7).4 This series of reactions, followed by... 

Benzyloxypropyl)phosphonic and (2-trimethylsilyloxyethyl)phosphonic diethyl esters are obtained from the appropriate alkyl bromide and triethyl phosphite. Deprotection at the side-chain substituent (debenzylation with H2, Pd-C desilylation with MeOH-HCl) leaves the diethyl (2-hydroxypropyl)- and (2-hydroxyethyl)-phosphonates from which the free acids are readily obtainable by acid hydrolysis. Both procedures were adapted by Hammerschmidt for the preparation of deuterium-labelled compounds of known chirality for biosynthetic studies. The acetyl group can also be used for protection purposes ... 

Michaelis-Arbuzov reactions are not restricted to the use of the alkyl halide but may also be carried out with a corresponding ester or alcohol. On reaction with triethyl phosphite or a phosphorus(III) amide, the ester NCCH2CH2Z (Z = OAc) and ethers (with Z = OPh or OEt) afford the corresponding derivatives of (2-cyanoethyl)phosphonic acid [3-(dialkoxyphosphinyl)propanenitrile]. The same products are obtainable from 2-cyanoethanol. These reactions, and the conversion of406 into 408 and of407 into 409 , are reminiscent of those which take place between phosphorus(III) esters and 2-hydroxy-benzyl alcohols, and indeed they may be formulated in a similar manner (Chapter 2, Section II.A). Yet a further variation in reaction 22 is the involvement of substrates in... 

In principle, the interaction of a phosphorus(III) ester with an co-haloalkylamine should lead to an (co-aminoalkyl)phosphonic diester or a phosphinic acid analogue (Scheme 11). Such examples in the classical Michaelis-Arbuzov mould have been widely reported, but success in their outcome depends on the relative nucleophilicities of nitrogen and phos-phorus(III) centres towards the displacement of halogen. The interaction of triethyl phosphite and a halogen-substituted tertiary amine, such as 2-chloroethyldiethylamine, does not lead to a phosphonic diester, and in this particular case the product is a piperazinium diquaternary salt. However, successful Michaelis-Arbuzov reactions have been carried out between the bis(bromomethyl)phthalazines 130 (to both the mono- and di-phosphonic acid stages) and the series of [co-(2-cyano-4-pyridine)alkyl]phosphonic diesters 132 (n = 1-4) have been prepared from the 4-pyridinealkyl bromides 131 as precursors to the phosphonoalkylpiperidinecarboxylic acids 133 . ... 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

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