287733-60-2Relevant academic research and scientific papers
Organocatalytic stereoisomerization versus alkene isomerization: Catalytic asymmetric synthesis of 1-hydroxy-trans -2,5-diphenylphospholane 1-oxide
Hintermann, Lukas,Schmitz, Marco,Maltsev, Olegv.,Naumov, Pance
supporting information, p. 308 - 325 (2013/03/14)
The potential for an organocatalytic asymmetric stereoisomerization or alkene isomerization as atom-economic reaction with minimal structural change was investigated. The McCormack cycloaddition of 1,4-diarylbuta-1,3-dienes with (dialkylamino)dichlorophosphane and aluminum trichloride gives meso-2,5-diaryl-1-(dialkylamino)-1-oxo-2,5-dihydro-1H-phospholes, which were identified as suitable substrates for asymmetric isomerization to (1R,5R)-2,5-diaryl-1-(dialkylamino)-1-oxo-4,5-dihydro-1H-phospholes in the presence of bifunctional organocatalysts (cinchona alkaloids, Takemoto catalyst) in up to 91% ee and quantitative yield. The substrate range and the mechanism of the catalysis were studied. The reaction involves proton abstraction by the base, but a primary deuterium KIE is absent. Enriched (1R,5R)-1-(diethylamino)- 1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole was hydrolyzed to (5R)-1-hydroxy-1-oxo-2,5-diphenyl-4,5-dihydro-1H-phosphole, which was hydrogenated diastereoselectively under dissolving metal conditions to give (2R,5R)-1-hydroxy-1-oxo-2,5-diphenylphospholane (Fiaud's acid) in preference to meso-1-hydroxy-1-oxo-2,5-diphenylphospholane. An asymmetric catalytic total synthesis of Fiaud's acid, which is a building block for chiral phospholane synthesis, has been realized in five steps from thiophene, using nickel-catalyzed Wenkert arylation, McCormack cycloaddition, asymmetric dihydro-1H-phosphole isomerization, hydrolysis, and diastereo-selective hydrogenation. Georg Thieme Verlag Stuttgart New York.
Cyclic five-membered phosphinate esters as transition state analogues for obtaining phosphohydrolase antibodies
Hum, Gabriel,Wooler, Krista,Lee, Jeremy,Taylor, Scott D.
, p. 642 - 655 (2007/10/03)
Two novel cyclic five-membered phosphinate esters (6 and 7) were synthesized and used as transition state analogues (TSAs) for raising phosphohydrolase antibodies. The key step in the syntheses was a McCormack reaction between (2-chloroethyl)dichlorophosphite and 1,4-diphenyl-1,3-butadiene to form isomeric cyclic phosphinyl chlorides which upon further elaboration yielded the TSAs. X-ray crystal structures of two cyclic phosphinate TSA precursors (14a and 14b) show highly compressed CPC bond angles of 94°-97° indicating that the CPC bond angles in 6 and 7 are significantly distorted towards the ideal trigonal bipyramidal equatorial-apical transition state angle of 90° formed during phosphate ester hydrolysis. Antibodies were raised to 6 and 7 using standard hybridoma technology. One antibody. Jel 541, an IgM class antibody, was obtained that was capable of catalyzing the hydrolysis of phosphonate substrate 9 and, to a much lesser extent, phosphate substrate 8. This antibody bound TSA 6 approximately 100 times more tightly than TSA 7 as determined by solid phase radio immune assays. The activity of the antibody-catalyzed reaction was completely inhibited by the presence of TSA 6. Although the relative instability and poor solubility of Jel 541 made it impossible to perform a detailed kinetic analysis of the antibody-catalyzed reactions, these results demonstrate that phospholydrolase antibodies can indeed be obtained using cyclic five membered phosphinates as haptens.
