Monosubstituted phosphate reactions

A sensitive probe applied to understand the nature of the reaction mechanism of group transfer is the stereochemistry of the overall reaction. The reaction at a phosphoryl center normally is a degenerate question, since a monosubstituted phosphate ester or anhydride is proprochiral at the phosphate center. Phosphate centers at a diester or disubstituted anhydride are prochiral. Two related methods to analyze the stereochemistry at a phosphate center have been developed by the generation of chirality at the phosphorus center. The first approach was developed by Usher et al. (24) and gave rise to the formation of isotopi-cally chiral [ 0, 0]thiophosphate esters and anhydrides (I). Isotopically chiral [ 0, 0, 0]phosphates (II) have also been synthesized and the absolute configurations determined. Two primary problems must first be addressed with respect to both of the methods that have been developed the synthesis of the isotopically pure chiral thiophosphates and phosphates and the analysis of the isotopic chirality of the products. An example of the chiral starting substrates, as developed for ATP, is schematically demonstrated. Ad = adenosine. 

Addition to linear 1,1-disubstituted allylic acetates is slower than addition to monosubstituted allylic esters. Additions to allylic trifluoroacetates or phosphates are faster than additions to allylic carbonates or acetates, and reactions of branched allylic esters are faster than additions to linear allylic esters. Aryl-, vinyl, alkynyl, and alkyl-substituted allylic esters readily undergo allylic substitution. Amines and stabilized enolates both react with these electrophiles in the presence of the catalyst generated from an iridium precursor and triphenylphosphite. 

In 2007, Terada et al. extended their previously described chiral phosphoric acid-catalyzed aza-ene-type reaction of M-acyl aldimines with disubstituted enecarbamates (Scheme 28) to a tandem aza-ene-type reaction/cyclization cascade as a one-pot entry to enantioenriched piperidines 121 (Scheme 48). The sequential process was rendered possible by using monosubstituted 122 instead of a disubstituted enecarbamate 76 to produce a reactive aldimine intermediate 123, which is prone to undergo a further aza-ene-type reaction with a second enecarbamate equivalent. Subsequent intramolecular cychzation of intermediate 124 terminates the sequence. The optimal chiral BINOL phosphate (R)-3h (2-5 mol%, R = 4-Ph-C H ) provided the 2,4,6-sub-stituted M-Boc-protected piperidines 121 in good to exceUent yields (68 to > 99%) and accomplished the formation of three stereogenic centers with high diastereo- and exceUent enantiocontrol (7.3 1 to 19 1 transicis, 97 to > 99% ee(trans)) [72]. 

To define the effectiveness of the UV/H202 process on a wide range of priority pollutants in water, Sundstrom et al. (1989) conducted experiments in a recirculating flow reactor system with low-pressure UV lamps at 254 nm. The temperature of the solution was maintained at 25°C, and pH was maintained at 6.8 by a phosphate buffer. Molar ratio of peroxide to pollutant was varied during the experiments. As the molar ratio of peroxide to pollutant increased, the reaction rates increased. Three monosubstituted benzenes were selected to examine the effect of a single substituent group on the rate of reaction of benzene. The rates of reaction were of similar magnitude for benzene and monosubstituted benzenes (toluene, chlorobenzene, and phenol) at the ratio of 7 for peroxide to pollutant. 

Reductive phosphorylation of p-benzoquinones (1, 1233). This reaction is generally improved by use of P(OCH,),/ClSi(CH,),. which provides p-hydroxyphenyl phosphates after methanolysis. Moreover, C-phosphorylation occurs to a minor extent with this modification. This reductive phosphorylation coupled with selective cleavage of the phosphoryl group with BrSi(CH,)3 (9, 74) provides a route to monoprotected hydroqui-nones from monosubstituted p-benzoquinones. 

The method described by Morrison and Bayse (1970) for the enzymic iodination of tyrosine can be readily adapted to the modification of proteins. The reaction mixture contains, in order of addition, L-tyrosine (8.1x10 M), KI (1.0 xlO M), lactoperoxidase (7.4 X 10 M), in 0.05 M K-phosphate buffer, containing 1 x 10 M EDTA, at pH 7.4. The iodination is initiated by the addition of H2O2 to a concentration of 1.0 x 10 M. The specific activity observed for lactoperoxidase under these conditions was 1.05 x 10 moles of L-3-iodotyrosine per min per mole of enzyme at 25°C. At pH 7.4, the rate of enzymatic conversion of L-3-iodotyrosine to L-3,5-diiodotyrosine was 0.34 that of monosubstitution (Morrison and Bayse 1970). The desired level of iodination can be attained by successive equimolar additions of KI and HjOj to the reaction mixture. In this manner, only a low concentration of H2O2 is maintained, minimizing oxidation reactions. The concentration of lactoperoxidase may be calculated from the millimolar extinction coefficient of 114 at 412 run, while the concentrations of stock H2O2 solutions may be determined from the absorbance at 230 nm and a molar extinction coefficient of 72.4 (Phillips and Morrison 1970). 

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