Phosphonamide ligands

Semirigid phosphonamide ligands have been synthesized from the corand precursors by the reaction of 1,3-propanediol ditosylate or 1,2-dichloroethane <96JOC8904>. 

With these substrates, achiral 1-24 is strongly favoured with Pd catalysts (for other metals, the situation is different) except in special cases. Diazaphos-pholidine-oxazoline 20 shows moderate performance in the alkylation of butenyl acetate compared to the exceptionally good results with SiocPhox phosphonamidate ligands for alkyl- and aryl-substituted substrates. The same type of ligands have also been applied to the alkylation of other challenging substrates such as polyenyl esters and acyclic ketone enolates. ... 

Asymmetric allylation and crotylation reactions using allylic trichlorosilanes and chiral phosphonamides were developed by Denmark and coworkers in 1994 and further refinement of the chiral ligands system was made in 200114 (Scheme 3.2k). The influence of the six-membered chairlike transition state is once again evidenced by the excellent correlation of the geometry of the reacting silanes with the diastereomeric composition of the products. Thus, anti -isomer is obtained from the -allylic silane, and syn-isomer is produced from the Z-silane. Based on... 

Bash et al. (1987) applied the thermodynamic perturbation method to complexes of thermolysin with a phosphonamidate [Cbz-Gly -(NH)-Leu-Leu] and the corresponding phosphonate inhibitor [Cbz-Gly -(0)-Leu-Leu]. The perturbation was carried out by using 20 windows, with 2-psec molecular dynamics simulations in each window. Computations were for the ligand in solution and bound to the enzyme. The solvation of the enzyme was represented by a spherical cap of 168 water molecules about the bound inhibitor. The difference in free energy of binding of the two inhibitors was calculated to be 4.38 kcal/mol, to be compared with the experimental value, 4.10 kcal/mol. These calculations point out the importance of solvation effects, which are seen in the 3.4 kcal/mol difference between the NH and O forms of the inhibitor. 

Conclusion. The C2 symmetry of (R,R)- and (S,S)-1,2-diaminocyclohexane, readily available from the racemic compound by resolution, has served as a versatile chiral motif in the design of topologically unique stereodifferentiating reagents such as the phosphonamide anions described here. Several other applications of these reagents via anion chemistry, or simply based on the exploitation of other effects offered by their structures and heteroatom functionality, can be explored (catalytic processes, chiral ligands, etc.). The lYfY-disubstituted 1,2-diaminocyclohexane motif has also been remarkably versatile in other asymmetric processes such as the dihydroxylation of alkenes, and a variety of other C-C bond-forming reactions. ... 

An early study on the hydrolysis of the cyclic phosphoramidate [65] in base demonstrated exclusive endocyclic P—O bond cleavage, in contrast with the P—N bond cleavage observed for the corresponding phosphonamidate [66] (Brown et al., 1976) (Scheme 24). This observation is consistent with the similar apical potentialities of oxy and azo ligands derived by Hall and Inch in their elegant stereochemical studies of similar cyclic compounds (p. 144). 

Phosphanorbomene and norbornadiene ligands with phosphonate or phosphonamide groups can be prepared by the addition of substituted phos-phole to ethynylphosphonates and ethynylphosphonamides, which gave both 5- and 6-substituted derivatives ... 

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