2,5-Dihydro-l,2-oxaphosphole-2-oxides

Abstract This chapter deals with the methods for the syntheses of 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives, and some recent results of their biological activity testing. The electrophilic addition to 1,2-alkadiene- and alkatrienephospho-nate derivatives is one of the easiest and fruitful synthetic strategies for obtaining these compounds in preparative amounts. 

Methods for Synthesis of 2,5-Dihydro-l,2-Oxaphosphole-2-Oxide Derivatives... 

Later Pudovik et al. synthesized 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives from the reaction of propynoic acid with ethyldichlorophosphine... 

Dihydro-l,2-oxaphosphole-2-oxide derivatives were the main products obtained from halogenation of dialkyl esters of 1,2-alkadienephosphonic acids (Scheme 37) [53, 69, 79, 81, 93-100],... 

Compounds 118 could be produced from the reaction of dialkyl esters of 3-monosubstituted-l,2-alkadienephosphonic acids with methylselenenyl chloride. It was established that, along with 118, 2,3-adducts were also formed [113]. Use of phenylsulphenyl chloride in this reaction leads exclusively to the formation of 2,5-dihydro- l,2-oxaphosphole-2-oxide derivatives 117 (Scheme 48) [113, 114]. 

The above results encouraged authors [95, 99] to examine the reactivity of dialkyl esters of 1,2,4- and 1,3,4-alkatrienephosphonic acids 169 and 170. These substrates on halogenation gave 3- or 5-vinylsubstituted-2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives 171 and 172 (Scheme 68). Spectral investigations of this reaction show that, formation of oxaphosphole ring starts immediately after adding of the reagent. 

Petrov and coworkers [41] showed that the reaction of dibromides of alkenephos-phonic acids with acetylenic alcohols involved an acetylene-allene rearrangement. The products so formed hydrolyzed easily to the corresponding phosphinic acids. The latter on heterocyclization afforded 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives (Scheme 11). 

All the synthetic protocols described above have limitations to some extent and the yields of the products were modest. In some cases the formation of 1,2-alkadi-enephosphonate derivatives is essential for obtaining the final cyclic products. This is the reason why many authors have used the higher reactivity of 1,2-alkadi-enephosphonates, discovered by Mark [42] in 1962 for the preparation of 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives. Since then, the oxaphospholic cyclization of 1,2-alkadienephosphonate system of double bonds has become the easiest method for the synthesis of these compounds. The special structure of phosphorylated allenes is responsible for their special properties, which has attracted the attention of chemists for a long time [43 16],... 

The reaction of 1,2-alkadienephosphonic acids with an electrophile E+ [H+, Br+/ CHC13, Hg(OAc)2/AcOH] leads to 2,5-dihydro-l,2-oxaphosphole-2-oxides (Scheme 24) [66-69],... 

The reaction of the 3,3-disubstituted-l,2-alkadienephosphonic dichlorides with alkylsulphenyl chlorides afforded, along with 2,5-dihydro-l,2-oxaphosphole-2-oxide derivatives, 1,2-adducts also. The use of sulfur dioxide in this reaction promoted the formation of the oxaphosphole product (Scheme 35) [22, 44, 71-73, 87-92],... 

Auch cyclische Phosphinsaure-ester lassen sich mit Grignard-Verbindungen umsetzen. So entsteht aus 2,5-Diphenyl-3-methyl-2,5-dihydro-l,2-oxaphosphol-2-oxid mit Phenyl-magnesiumbromid Diphenyl- (3-hydroxy-1 -methyl-3-phenyl-l-propenyl)-phosphan-oxid (Schmp. 154-156°) zu 77%2 6 ... 

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