Aromatic phosphoramidates

As mentioned in last year s Report, aromatic phosphoramidates have been used to protect 5 -phosphoryl groups in the stepwise synthesis of oligodeoxyribonucleotides. The appropriate monomer units are coupled with DCC and the phosphoramidate protecting group is removed when required with isoamyl nitrite. A rapid and general preparative method for oligonucleotides has been developed based on phosphoramidates of the highly lipophilic 4-aminophenyltriphenylmethane (25). Purification of... 

Chloro- and A TV-dichloro-phosphoramidate esters (20) and (21) are readily prepared from the parent phosphoramidate by direct chlorination in mildly acidic solution but when R = Ph, the use of t-butyl hypochlorite is preferable, to avoid chlorination of the aromatic nucleus. These compounds behave as pseudohalogens, (21) reacting with olefinic compounds such as styrene to give (22), which is also formed by chlorination of the N-phosphorylaziridine (23). ... 

In a new approach to the synthesis of phosphoramidates by the Todd-Atherton reaction, those from the more weakly basic amines, more particularly aromatic amines, have been obtained by... 

The reaction of 151 with methanol to give dimethyl phosphate (154) or with N-methylaniline to form the phosphoramidate 155 and (presumably) the pyrophosphate 156 complies with expectations. The formation of dimethyl phosphate does not constitute, however, reliable evidence for the formation of intermediate 151 since methanol can also react with polymeric metaphosphates to give dimethyl phosphate. On the other hand, reaction of polyphosphates with N-methylaniline to give 156 can be ruled out (control experiments). The formation of 156 might encourage speculations whether the reaction with N,N-diethylaniline might involve initial preferential reaction of monomeric methyl metaphosphate via interaction with the nitrogen lone pair to form a phosphoric ester amide which is cleaved to phosphates or pyrophosphates on subsequent work-up (water, methanol). Such a reaction route would at least explain the low extent of electrophilic aromatic substitution by methyl metaphosphate. 

Denmark utilized chiral base promoted hypervalent silicon Lewis acids for several highly enantioselective carbon-carbon bond forming reactions [92-98]. In these reactions, a stoichiometric quantity of silicon tetrachloride as achiral weak Lewis acid component and only catalytic amount of chiral Lewis base were used. The chiral Lewis acid species desired for the transformations was generated in situ. The phosphoramide 35 catalyzed the cross aldolization of aromatic aldehydes as well as aliphatic aldehydes with a silyl ketene acetal (Scheme 26) [93] with good yield and high enantioselectivity and diastereoselectivity. 

Several considerations recommended their employment (a) aromatic amines readily displace the more strongly basic aliphatic amines from phosphoramidic monoesters54 (b) the transition state for displacement would require the accommodation of phosphorus and the entering and leaving groups in a five-... 

N, N-Bis(2-oxo-3-oxazolidinyl)-phosphoramidic chloride, 39 Hexamethyldisilazane, 141 Thionyl chloride, 297 Zirconium(IV) acetylacetonate, 351 of aromatic rings Lithium o-lithiophenoxide, 166 of compounds containing active hydrogens... 

Asymmetric aldol additions of geometrically defined trichlorosilyl enolates of ketones to aliphatic and aromatic aldehydes have been carried out uncatalysed, and with a chiral phosphoramide as Lewis base promoter.54 Significant differences in rates and diastereoselectivities are interpreted in terms of the changeover from a boat-like transition state, with pentacoordinate siliconate, to a chair-like transition state with hexacoordination. 

S)-Prolinc-dcrivcd phosphoramides catalyse enantioselective allylation of aromatic aldehydes with allylic trichlorosilanes.90 Chiral a-aminoaldehydes have been allylated diastereoselectively with various reagents.91... 

Stereo specific generation and reactions of allylic alkali and alkaline earth metals have been reviewed121 and solvent-mediated allylation of carbonyl compounds with allylstannanes has been explored.122 Chiral phosphoramides derived from (5 )-proliiie have been used to catalyse asymmetric allylation of aromatic aldehydes by allylic trichlorosilanes.123... 

Chiral Lewis-basic catalysts (Figs. 7.1 and 7.2), in particular phosphoramides 8-12 [9, 14c, 15c, 22-24], formamide 13 [17], pyridine N,N -bisoxides 17 and 18 [25-27], N-monoxides (19-26) [27-32], and N,N N"-trisoxides (27) [33] exhibit good to high enantioselectivities for the allylation of aromatic, heteroaromatic, and cinnamyl-type aldehydes (1) with allyl, trans- and ds-crotyl, and prenyl trichlorosilanes (2a-d). Chiral formamides (with the exception of 13, as discussed below) [17], pyridine-oxazolines [34], urea derivatives [19] and sulfoxides [35] are effective only in stoichiometric quantities (or in excess) and, as a rule, exhibit lower enantioselectivities. 

For aromatic amines (pyridines and imidazole), phosphoramidates were not detected in water. Yet the reaction appears to be essentially the same as in the former cases, because the formation of phenyl-methylphosphate, which was observed in methanol, was presumed to occur by the methanolysis of phosphoramidate. 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

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