Lewis acid catalysts phosphoramide activation

Based on the same strategy, Denmark and coworkers developed a vinylogous aldol reaction using enolate activation with a catalyst derived from SiCl4 and dimeric phosphoramide 47 [24,25]. This strategy relies on the observation that not all Lewis acid - Lewis base interactions diminish the Lewis acidity [26-28]. Due to the formation of a pentacoordinated silicon cation (48), both the enolate and the substrate can be assembled in a closed transition state, giving rise to the observed high selectivities (Scheme 19) [29,30]. 

An analogous propargylation can be attained with allenyl tributyl stannane however, this reaction is catalyzed by SiCU that is activated by a bisphosphor-amide catalyst. Note that in this case, the role of the Lewis basic phosphoramide is to increase the Lewis acidity of SiCU rather than to increase the nucleophilicity of the stannane [51b]. A discussion of these effects is provided in Section 7.4. 

A related reaction is the addition of isonitriles 75 to aldehydes 1 (the Passerini reaction). Denmark has demonstrated that SiCU, upon activation by a chiral Lewis base, which increased the Lewis acidity of the silicon (vide supra Scheme 7.14), can mediate this reaction to produce a-hydroxy amides 77 after aqueous work-up (Scheme 7.16). Phosphoramide 60 was employed as the chiral Lewis-basic catalyst [74]. Modification of the procedure for hydrolysis of 76 gives rise to the corresponding methyl ester (rather than the amide 77) [74]. (For experimental details see Chapter 14.5.5). 

The novel mode of Lewis-hase activation of Lewis acid was also applied hy Denmark to the Passerini reaction, the addition of isonitriles 21.119 to aldehydes 21.4 (Scheme 21.17). This reaction produced a-hydro g amides 21.121 after aqueous workup. Phosphoramide 21.104 was employed as the chiral Lewis-hasic catalyst.Modification of the procedure for hydrolysis of 21.120 gives rise to the corresponding methyl ester (rather than amide 21.121). ... 

With the synergistic effect of Lewis base and Lewis acid, Denmark and coworkers have established several successful organic catalyst systems based on the strategy of Lewis acid activated Lewis base or Lewis base activation of Lewis acid, in which chiral phosphoramides expressed excellent diastereo- and stereoselectivity for the aldol reaction of silyl enolates and aldehydes (Scheme 65) (311-313). 

Ishihara and coworkers also reported mixed zinc reagents, namely PhjZn/EtjZn, as the phenyl source for enantioselective phenyl additions to ketones (Scheme 7.51). The cat2ilyst was a chiral phosphoramides-Zn(II) complex prepared in situ [81]. These chiral Zn(II) cat2ilysts serve as conjugate Lewis acid-Lewis base catalysts (Figure 7.10). From a variety of aromatic and aliphatic ketones, optically active tertiary alcohols were obtained in high yields with high enantioselectivities (up to 98% ee) under mild reaction conditions (Scheme 7.51). 

In the catalytic cycle, a simplified version of which is shown in Scheme 5.72 for the acetate aldol addition of 246, the highly electrophilic silyl cation 251 plays a key role, as assumed by the authors. It forms from the reaction of tetrachlorosilane with the corresponding phosphoramide ((Me2N)3PO symbolizing the catalyst 235). When loaded with benzaldehyde, silicon enlarges its coordination sphere and adopts an octahedral geometry in 252. After the carbon-carbon bond has been established, cation 253 forms. It then decomposes to liberate phosphoramide 235, chlorotrialkylsilane, and the aldolate 254. By NMR studies, it was shown that the intermediate of this procedure is the tric/i/orosilyl-protected aldolate 254. This makes a substantial mechanistic difference to conventional Lewis acid-catalyzed Mukaiyama aldol protocols that deliver tri /Ay/silyl-protected aldolates. In accordance with the catalytic cycle shown in Scheme 5.72, tetrachlorosilane is consumed and therefore required to be used in stoichiometric amounts. Thus, the reaction is catalyzed by phosphoramides and mediated by tetrachlorosilane or, more generally, by Lewis base-activated Lewis acids [126]. 

The asymmetric catalysis of aldol reactions with chiral Lewis bases is an important method to form C-C bonds [130-139], The emergence of Lewis base-activated Lewis acid catalysis is pioneered by the Denmark group [140-142], They used a variety of chiral phosphoramides as catalysts for the enantioselective intermolecular aldol reactions (Scheme 7,20),... 

Prior to Yamamoto s entry into this field, the scope of chiral phosphoric acid catalysis was strictly limited to electrophiUc activation of imine substrates. By designing a catalyst with higher acidity it was suspected that activation of less Lewis basic substrates might be possible. To this end, Yamamoto reported incorporation of the strongly electron accepting N-triflyl group [57] into a phosphoric acid derivative to yield the highly acidic N-triflyl phosphoramide 13 (Scheme 5.32)... 

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