Spirophosphoranes, activation

Electrophilic addition to spiro phosphenium cations 258 provides a route to spirophosphoranes. However, only very active electrophiles are suitable, for example, benzenesulfonyl azide which on reflux in acetonitrile with 258 yields 259 (Equation 70) <1998RJC530>. 

Details have appeared39 of the addition of PH-tetraoxyspirophosphoranes to aldehydes and activated ketones. These phosphoranes also add to activated acetylenes,40 e.g. diethyl acetylenedicarboxylate with (50) gives a mixture of cis- and trans-(51). Further addition of (50) to (51) at higher temperatures gives the bisphos-phorane (52). Metallation of the spirophosphorane (53) followed by reaction with... 

The synthesis of an optically active chiral phosphorane in which the optical activity is solely connected with the P atom implies, for instance, the preparation of a trigonal bipyramid or a tetragonal pyramid with five different achiral ligands which would, at least theoretically, entail the possible formation in the first case of ten or in the second case of fifteen diastereoisomers requiring separation, a formidable task even in the absence of stereomutation. The problem has nevertheless been solved using three different approaches exploiting the particular properties of spirophosphoranes, as hereafter detailed. 

Even if some of the optically active spirophosphoranes mentioned above can exist as single species in the solid state, all of them are more or less rapidly transformed, when dissolved, into binary mixtures of diastereoisomers114-129 such as 12 and T3. However, a third type of synthesis yielded pure, optically active phosphoranes not subject to change when dissolved129. This was obtained by the stereospecific synthesis of the oxazaphos-pholidine 53130 (Scheme 5) derived from the —(1R, 2S)enantiomer of ephedrine by means... 

A New Approach to Activation of Hydroxy Compounds Using Pentacoordinated Spirophosphoranes... 

According to these findings it was clear that an optically active spirophosphorane of that type was only possible if at least one unsymmetrically substituted 2,2 -biphenylylene ligand was present. Only then, as is shown in the next scheme, the Berry process involving tetragonal-pyramidal transition state C will not lead to raeemization, since now the trigonal bipyramids B, B are no longer enantiomers but diastereomers. 

A series of bis cyclotriphosphazenyl spermines such as (161) have been prepared and shown to have anticancer activity in six murine tumour systems. These compounds had a higher potency and lower toxicity than related aziran derivatives <87PS(29)147). Spirophosphorane derivatives of thymidine such as (162 R = CF3) have been used as models for the study of the stereochemistry of cyclic AMP interactions with enzymes <90JA6092>. The base catalyzed proton transfer observed for the equilibrium shown in Scheme 23, mimics the role of the bases histidine 12 and histidine 119 in the active site of Rnase A during the hydrolysis of ribonucleic acids <84PS(19)173>. 

This is contrary to McClelland s conclusions, based on kinetic analysis of spirophosphoranes. These contradictory statements serve to highlight the most significant gap in our knowledge of the reaction profile of nucleophilic substitution via a TBP phosphorus intermediate. Theoretical calculations and empirical observations have permitted evaluation of barriers to interconversion of reactive intermediates. However, the activation barriers for formation of the initial intermediate and breakdown of the final intermediate are far less certain. 

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