Phosphines acylphosphine

The heterocyclic acylphosphines (52) and (53) have been prepared by the reaction of phenylbis(trimethylsilyl)phosphine with the acid chlorides derived from phthalic and diphenic acids. The reaction of 2,3-dichloromaleic anhydride or thioanhydride with phenylbis(trimethylsilyl)phosphine gives derivatives of the 1,4-dihydro-p-diphosphorin system (54).45... 

Alkyl ethers of benzoin Benzil dimethyl ketal 2-Hydroxy-2-methylphenol-l-propanone 2,2-Diethoxyacetophenone 2-Benzyl-2-At, V-dimethylamino- l-(4-morpholinophenyl) butanone Halogenated acetophenone derivatives Sulfonyl chlorides of aromatic compounds Acylphosphine oxides and bis-acyl phosphine oxides Benzimidazoles... 

Quite a dilferent reaction of acetyldiphenylphosphine (4) is responsible for the formation of the oxide (5) from acetic acid and chlorodiphenylphosphine. The phosphine (4) is shown (Scheme 1) to be an intermediate in the reaction, and to undergo an unexpected addition of acetic acid to form (5). The involvement of an acylphosphine is the essential difference between the reactions of chlorodiphenylphosphine with acetic acid and with trifluoroacetic acid the latter produces (3). ... 

Chlorotris(triphenylphosphine)rhodium(I) Phosphines from acylphosphines Decarbonylation... 

Phosphines of entries 8 and 9 are examples of compounds whose configurational stability is inferior due to other effects. Acylphosphines (entry 8) have inferior inversion barriers due to conjugation in the planar transition state." Comparison between entries 7 and 9 shows a dramatic lowering of inversion energies in phospholes compared to phospholanes, probably caused by an increase in the delocalisation of the planar transition state in the phosphole inversion. " In spite of that, more conjugated fused phospholes (entries 10 and 11) are more configurationally stable. 

Tris(TMS)phosphine reacts with methyl chloroformate under mild conditions to formbis(trimethylsilyl)methoxycarbonylphos-phine and tris(methoxycarbonyl)phosphine (or mixtures thereof) depending on the equivalents of methyl chloroformate used (eq 13). In contrast to acylphosphines 1, which readily undergo a phosphorus to oxygen 1,3-shift of a TMS group, compound 3 is stable and does not isomerize (eq 13). 

Acylphosphines can be prepared through the metal-free treatment of acyl chlorides with secondary phosphines (Scheme 4.316) [480]. This approach is high yielding... 

It was recognized that an acylphosphonate or acylphosphinate might act as an effective inhibitor against plant PDHc. Both compounds could compete with pymvate for the active site of plant PDHc El by binding with TPP resulting a TPP complex. It was speculate that, a highly reactive carbanion of TPP should nucleophiUcaUy attack carbonyl carbon atoms of 1-2 to readily form a phosphinic adduct which resembled normal reactive intermediate a-lactyl-TPP. Once it was bond, the normal decarboxylation process in plant was shut off and plant die as their... 

Although these acylphosphinates and acylphosphonates were not active enough to be considered as herbicides, the SAR analysis provided a clue in designing better OP PDHc El inhibitors with better herbicidal activities. Data suggested that the phosphonate molecule played a very important role in plant PDHc El inhibition. We also noticed that acylphosphonates had better selectivity for plant PDHc El between mammals and plant than its acylphosphinates counterpart. For example the sodium O-methyl acetylphosphonate 1-1 was a much weaker inhibitor against human PDHc El compared to that of sodimn acetyl(methyl)phosphinate 1-2 and sodimn acetylphosphinate 1-3 (Table 1.6). Therefore, 1-1 that happens to be the best inhibitor in this group, deserves further modification and optimization. 

Bioisosterism is an important aspect in designing bioactive compounds. For example, phosphinate unit is often used to replace the phosphonate unit to obtain a more active compound. Bailie et al. s SAR analyses showed that the replacement of methoxyl in acylphosphonate (1-1) by methyl to produce acylphosphinate (1-2), would significantly improve the inhibitory potency and herbicidal activity. Therefore, we were interested in examining herbicidal activity of the alkylphosphinates. On the basis of (9,(9-dimethyl 1-(substituted phenoxyacetoxy)alkylphosphonates IC, several novel series of (9-methyl [1-(substituted phenoxyacetoxy)alkyl]meth-ylphosphinates lllA-lllG including 54 compounds were designed and synthesized (Scheme 1.29). 

A detailed study of acylphosphinates and acylphosphonates showed that they were mechanism-based inhibitors of pyruvate dehydrogenase complex (PDHc) as analogues of pyruvate. However, these phosphinates and phosphonates were not active enough to be considered as herbicides [1-3]. As stated in Chap. 2, some 1-substituted alkylphosphonates IC and IG showed notable herbicidal activity. Furthermore, the substitution of R R, R, R" and Y in phosphonate lo could be directly relevant to their herbicidal activity. Among the 1-substituted alkylphosphonates lA-IC, IC-22 (clacyfos) was found to be most eflFective against broadleaf weeds as a competitive inhibitor of PDHc (Scheme 3.1) [4]. This result prompted us to study continually on the design of novel PDHc inhibitors as potential herbicides. 

Interesting rhodium-catalyzed interconversions were studied between acylphosphine sulfides and acid fluorides, acid thioesters and acid esters. In the first place, diethyl-(4-dimethylaminobenzoyl) phosphine sulfide (A) was reacted with 4-methoxybenzoyl fluoride (B) in the presence of 2 mol% of RhH(PPh3)4 and 4 mol% of TEDPDS in refluxing chlorobenzene. Under such conditions, 70% of the starting materials was recovered and ca. 19%... 

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