1.3- Oxaphospholes

The second chapter Synthesis and Biological Activity of 2,5-Dihydro-1,2-Oxaphosphole-2-Oxide Derivatives deals with the recent synthetic methods, particularly those using phosphorylated allenes as the starting materials, of these compounds which show interesting biological properties. 

Keywords 1,2-Alkadienephosphonates 1,2-Alkatrienephosphonates 1,2-Oxaphosphole Oxaphospholic cyclization... 

Methods for Synthesis of 2,5-Dihydro-1,2-Oxaphosphole-2-Oxide Derivatives. 24... 

The reaction of diacetone alcohol 1 with alkyldichlorophosphines afforded 3-chloro-l,2-oxaphospholane-2-oxide 2. The latter undergo isomerization followed by dehydrochlorination to the corresponding 1,2-oxaphosphole derivatives 3 (Scheme 1) [29],... 

The same authors also reported the preparation of 1,2-oxaphosphole derivatives from the reaction of alkyl(phenyl)dichlorophosphines with unsaturated ketones (Scheme 4) [33],... 

Scheme 5 Synthesis of 5-alkyl-3-methyl-2-phenyl-5//-[l,2]-oxaphosphole-2-oxides 11 and of 4-alkyl-2,5-diphcnyl-5//-[ 1,2]-oxaphosphole-2-oxides 13...

As underlined above, formation of these compounds by halogenation of dialkyl esters of 1,2-alkadienephosphonic acids is the major direction of the reaction. Even in the case of dialkyl esters of propadienephosphonic acid, some 1,2-oxaphosphole derivatives could be detected [86], On using sulfuryl chloride as electrophilic reagent, only 3,3-disubstituted- and 3-monosubstituted substrates could be transformed in oxaphosphole derivatives [39], Thus, the main role of the substituent at the C3 atom of the allenephosphonate system, for the formation of 2,5-dihydro-l,2-oxa-phosphole-2-oxide derivatives, was demonstrated. 

A similar procedure was employed [81,101] for the synthesis of iodine-substituted 1,2-oxaphospholes (Scheme 38). 

Oxaphospholic derivatives were also prepared from the reaction of 3-monosub-stituted alkadienephosphonates with alkylsulphenyl chlorides (Scheme 44) [107],... 

On reacting 3,3-disubstituted-l,2-alkadienephonic dialkyl esters with methyl-sulphenyl chloride, 1,2-oxaphosphole derivatives and 1,2-adducts were isolated [108], In the case of dialkyl esters of 3-methyl-1,2-butadienephosphonic acid, the formation of dialkyl esters of 1,3-butadienylphosphonic acid was also detected (Scheme 45). 

Regardless of the nature of the ester groups at phosphorus in the molecules of the 1,2-alkadienephosphonic substrate, the electrophilic addition leads to the formation of 1,2-oxaphosphole derivatives (Scheme 50) [116]. 

Enchev et al. [128,129] has reported the synthesis of 1,2-oxaphosphole derivatives, bearing /V./V-dtalkylamido-group at phosphorus 154 (Scheme 62). 

This synthetic strategy makes the synthesis of amino derivatives of 2,5-dihydro-1,2-oxaphospholes possible. 

The synthetic strategy described allowed the synthesis of /V-morpholino-1,2-oxaphosphole derivatives [134], as well as 1,2-oxaphosphole derivatives, bearing lV-2-chloroethyl group at phosphorus (Scheme 64) [135],... 

Compounds 181 react with alkylsulphenyl chlorides to form a mixture of 1,2-oxaphosphole derivatives and 1,2-adducts in 4 1 ratio. Decreasing the reaction temperature favored formation of oxaphosphole product. The same substrates reacted with phenylsulphenyl- and phenylselenenyl bromides to give only 1,2-oxaphosphole derivatives [133],... 

The reaction of 3,3-disubstituted-l,2-alkadienephosphinic acids with HC1 was also used to prepare the corresponding 1,2-oxaphosphole derivatives (Scheme 20) [63, 64],... 

Macomber has described the oxidation of 3-methyl-l,2-butadienephosphonic acid with 3-chloroperbenzoic acid to the corresponding cyclic allenic oxide, which undergoes rearrangement to produce the corresponding unstable 2,5-dihydro-1,2-oxaphosphole-2-oxide derivative (Scheme 25) [66],... 

On the basis of X-ray analysis of 1,2-oxaphosphole derivatives authors suggested [68] that these compounds have planar symmetry or that there is a process of rapid conformational equilibrium. 

By slow spinning band distillation in each case (R=CH3, CgHg) the two compounds corresponding to the two 31p nmr signals were separated with the major product in both instances having the downfield Up nmr chemical shift (R=CH3 6 31p + 75.1, 36% yield R=C H, 6 31P + 65.9, 58% yield). These compounds were identified spectroscopically ( H and 13c nmr, MS, IR) and by microanalysis as the expected 1,2-oxaphosphol-4-ene derivatives of the reaction of eq (1). ... 

Das cyclische Additionsprodukt von 2-tert.-Butyl-l,3,2-oxathiaphospholan und 3-Benzyliden-2,4-dioxo-pen-tan zerfallt beim Erhitzen auf 100 unter Bildung von 4-Acetyl-2-tert.-butyl-5-methyl-3-phenyl-2,3-dihydro-1,2-oxaphosphol-2-oxid5>B ... 

Oxaphosphol 2-Phenyl-3,3,5-trimethyl-2,3-dihydro- -2-sulfid E2, 257 (ArPCI2 + HS-CR2-CH2-CO-CH3)... 

The electronic structure and the aromaticity of 1,2-azaphosphole, 1,2-oxaphosphole, 1,2-thiaphosphole, and 1,2-diphosphole have been theoretically investigated in terms of aromatic stabilization energies (ASEs), resonance energies (REs), magnetic susceptibility exaltations, and nucleus-independent chemical shift (NICS) indexes <2002JOC1333>, as well as based on isodesmic reactions <2003T1657>. 

The 1,2-oxaphosphole 16 was formed quantitatively in the reaction of the oxadiphosphole 14 with dimethyl acetylenedicarboxylate (Scheme 6). It is highly sensitive and could not be isolated in a pure state by distillation or column chromatography <1999EJ0587>. 

Further reports have appeared on the reaction of trivalent phosphorus compounds with acetylene dicarboxylates. In the first, alkyl diphenylphosphinites (e.g.57) are shown to react with dialkylacetylene dicarboxylates (e.g.58) in the presence of carbon dioxide to form 1,2-oxaphosphol-3-enes (e.g.59) which in the presence of excess phosphinite decompose via (60) to give di-ylids (e.g.61). On the other hand, the phosphoranes (62) from phosphonites and phosphites react with a further phosphorus component to give the ylids (63) which are readily converted by treatment with alcohol into phosphonates (65) apparently via ketene intermediates (64) as evidenced by and isotopic tracer studies. ... 

Some reactions of 1,2-oxaphosphol-3-ene 2-oxides have been reported. When brominated under free radical conditions,... 

In the equilibrium reaction of trimethyl phosphite with benzylideneacetophe-nones to produce 1,2-oxaphospholes 110 the second-order rate constants for the formation of 110 have been determined using a polarography method, and the rate constants for the decomposition reaction were calculated from the equilibrium constants,... 

Dialkyl [2-chloro-2-(1-cyclohexenyl)ethenyl]phosphonates with alkyl (or aryl) sulphenyl chlorides afford derivatives of che bicyclic 5,6,7,8,9,10-hexahydro-2H-l,2-benzoxaphosphorin (205) rather than spirocyclic 1,2-oxaphospholes. ... 

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