Phosphoramides epoxide ring opening

Next to the above presented use of SiCl for the in situ preparation of a Lewis acid catalyst with a Lewis base for the aldol reaction, it is possible to apply this compound as a reagent in the ring opening of epoxides leading to chlorinated alcohols. Denmark [104] reported that the chiral phosphoramide 38 catalyzed the asymmetric ring opening reaction of meso-epoxides in the presence of tetrachlo-rosilane. Similar examples were provided by Hashimoto in 2002 [105], applying the A -oxide 39 as catalyst (Scheme 30). 

Denmark further applied this concept of chiral diamine-derived phosphoramide bases to catalytic diastereo- and enantioselective aldol reactions (Sch. 60) [103] and enantioselective ring opening of epoxides (Sch. 61) [104]. For instance, catalytic 84 effectively promotes aldol coupling of aldehydes and enoxytrichlorosilane at -78 °C with predominant formation of anti or syn aldols from ( )- or (Z)-enolates, respee-tively. 

Denmark et al. have extended this study to the enantioselective ring opening of meso-epoxides with silicon tetrachloride catalyzed by chiral phosphoramide 71 (Table 11). In this case, enantiomerically enriched chlorohydrins have been synthesized in enantiomeric excesses varying from 7 to 87 depending on the structure of the considered substrate [68]. 

Desymmetrization with halogen nucleophiles was effectively demonstrated with two mechanistically-divergent chiral catalysts. Denmark disclosed a Lewis-base activated delivery of chloride that was catalyzed by the enantiopuxe phos-phoramide 16. Binding of the phosphoramide was believed to induce dissociation of SiCl4 into the chiral phosphorus/silicon cation and chloride anion, which subsequently ring-opened the activated epoxide. The best enantioselectivity was observed with cfs-stilbene oxide, which was formed in 94% yield and 87% ee (Scheme 14) [28]. 

Among the more interesting developments in ring-opening reactions of epoxides (oxiranes, oxacyclopropanes) has been the observation that the process can be made enantioselective by the use of suitable Lewis acid-base pairs. Thus, with silicon tetrachloride in the presence of HMPA [(Me2N)3P=0], chlorohydrins can be generated. Then, if one enantiomer of a chiral phosphoramidate (such as the bis-... 

In addition, this class of chiral phosphoramides could catalyze the enantioselective ring opening of epoxides with silicon tetrachloride (SiCfl) [4]. For instance, the reaction of ds-stilbene oxide with SiCl, proceeded smoothly in the presence of 1 to afford the desired chlorohydrin in an enantiomericaUy enriched form (Scheme 7.3). The reactive ion pair shown in the scheme was proposed to be generated through the activation of SiCl, by the coordination of one phosphoramide 1, serving to activate the epoxide it was confirmed that bis-phosphoramide 2 was far less selective in this reaction. 

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