Diastereomeric phosphoramidates

Diastereomeric phosphoramides have been employed to catalyse the asymmetric aldol addition of trichlorosilyl enolates to benzaldehyde. Good anti/syn product ratios were achieved, but these were reversed on employing a more hindered catalyst, and the ratios were also affected by the catalyst concentration. A mechanistic switchover is proposed one transition-state geometry involves a 1 1 complex (cat-alyst enolate) favoured by a hindered catalyst in low concentration, while the other route involves a 2 1 stoichiometry. 

Aldol reactions using phosphoramides as organocatalysts The organic base-catalyzed asymmetric intermolecular aldol reaction with ketone-derived donors can be successfully applied to the construction of aldol products with two stereogenic centers [82-86]. Trichlorosilyl enolates of type 51 have been used as nucleophiles. Such enolates are strongly activated ketone derivatives and react spontaneously with several aldehydes at —80 °C. A first important result was that in the aldol reaction of 51 catalytic amounts of HMPA led to acceleration of the rate of reaction. After screening several optically active phosphoramides as catalysts in a model reaction the aldol product anti-53 was obtained with a diastereomeric... 

A new perspective was opened up recently when Denmark demonstrated diat with chirally modified phosphoryl-activated allenes an asymmetric induction could be effected. From easily generated allenyl phosphoramidates containing an optically active amino alcohol, the diastereomeric adducts (37) and (39) could be obtained by addition of dlyl alcohol. When the separated adducts were employed in the carb-anionic Claisen rearrangement, a remarkable asymmetric induction (90 10) could be achieved with preferential formation of the diastereomers (38) or (40) respectively, whereas in a thermal reaction no stereoselection was observed (Scheme 63). Another example of an asymmetric induction in Claisen rearrangements is reported by Welch. ... 

It is of interest that the commercially available chiral phosphoramide shown in Fig. 7, when employed in comparison reactions, afforded no observable diastereomeric differentiation either by P- or H-NMR spectroscopy [121]. This result may be rationalized on the fact that the monocyclic reagent has only two chiral centers while li possesses three. Moreover, the chiral centers in li are held rigidly in place, thus perhaps providing an enhanced chiral phosphorus environment. 

Similar 0-atyl-phosphoramidate derivatives of nucleosides, bearing an amino acid residue, were prepared in several laboratories. Synthesis of such a prodrug form of l, 2 -cyclopentyl nucleosides 44 was reported from the already mentioned Qun Dang s group. Conformationally-restricted 2 -spironucleosides (bearing a 2 -oxetane motif) and their prodrugs 45 were synthesised and tested. It should be emphasised that P-diastereomerically pure compounds were evaluated. The prodrugs of a 2 -oxetane 2-amino-6-0-methylpurine nucleoside demonstrated potent anti-HCV activity in vitro. 

The first example of an enantiopure Lewis base promoted allylation was reported by Denmark and coworkers in 1994 [46]. Stoichiometric amounts of the enantiopure phosphoramide (R,R)-20 promoted the enantioselective allylation (Scheme 16.13). There was a complete stereochemical correlation between the geometry (E/Z) of allylsilane and the diastereomeric ratio (syn/anti) of the products. 

Experimentally, the stereoelectronic effect on P shifts can be confirmed by using six-membered-ring model systems in which the torsional angles are rigidly defined by some molecular constraint, such as the two diastereomeric phosphate triesters 10 and the phosphoramidates 11 (Gorenstein, 1978,... 

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