N-triflyl phosphoramide

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)... 

Yamamoto also applied N-triflyl phosphoramide 13b to the 1,3 dipolar addition of various electron-deficient diaryl nitrones and ethyl vinyl ether (Scheme 5.33)... 

Thereafter, Yamamoto reported the first metal-free Bronsted add catalyzed asymmetric protonahon reachons of silyl enol ethers using chiral Bronsted acid 13c in the presence of achiral Bronsted add media (Scheme 5.34) [61]. Importantly, replacement of sulfur and selenium into the N-triflyl phosphoramide increases both reactivihes and enanhoselectivihes for the protonation reaction. 

Rueping employed N-triflyl phosphoramide 13d in the Nazarov cydization to afford cis-cyclopentenones with moderate diasterselechvihes in excellent yields and ee s. This represents the first example of an organocatalytic electrocyclizahon reaction [62]. Notably, related asymmetric metal-catalyzed Nazarov cyclizations often provide the trans-product [63]. Later, Rueping applied N-triflyl phosphoramide 13e... 

Scheme 6.17 AFC reaction of electron-rich arenes with ethyl glyoxylate imine catalyzed by chiral N-triflyl phosphoramide reported by Enders.

Brpnsted acids such as thioureas represent hydrogen bonding catalysts (vide infra), while phosphoric acids, N-triflyl phosphoramides, and dicarboxylic acids are examples of stronger specific Brpnsted acids. In this section, examples of processes mediated by stronger Br0nsted acids are presented, focusing on phosphoric acids, A-trifiyl phosphoramides, and dicarboxylic acids (Figure 7). 

Stronger Brpnsted acid catalysts such as N-triflyl phospho-ramides. N-Triflyl phosphoramides were first apphed to the asymmetric Diels-Alder (DA) reaction of unsaturated ketones with silyloxydienes. While the established phosphoric acids demonstrated no catalytic activity, 5 mol% of N-triflyl phosphoramide 46 proved highly effective for the DA reaction of ethyl vinyl ketone with a range of sily-loxydienes, allowing access to highly enantioenriched endo products in good yields (35 to >99%, 82-92% ee) via a presumed boat transition state such as 47 (Scheme 7). 

In 2013, another intramolecular hydrosilojqrlation was combined with a Mukaiyama aldol condensation by Gong et al. in an enantioselective relay catalytic cascade. This domino reaction occurred between atylacetylene silanols and glyoxylates and was induced by a combination of an achiral gold catalyst and a chiral N-triflyl phosphoramide. As shown in Scheme 7.37,... 

Although phosphoric acid has been employed for the activation of carbon-nitrogen double bond, Yamamoto et at. designed a stronger chiral Bronsted acid in order to expand the scope of the chiral Bronsted acid catalyzed reactions. A N-triflyl phosphoramide (50), bearing BINOL backbone, catalyzed the Diels-Alder reaction of a,p-unsaturated ketone with electron-rich diene ((2, )-siloxydiene is major) to give cyclohexene derivatives in high ees (Scheme 2.106) [184]. 

Quite recently. Rueping et al reported Nazarov cyclization reaction catalyzed by a phosphoramide (Scheme 2.107) [185]. Although phosphoric acid (41k) is effective for the Nazarov reaction, use of an N-triflyl phosphoramide (50b) improved the enantioselectivity. This is the first example of the enantioselective organocatalytic electrocyclization reaction. 

The Nazarov reaction belongs to a type of 4n electrocyclization and can usually be promoted by metal-based catalysts. In 2007, the first enantioselective organo-catalytic Nazarov reaction was reported by Rueping and coworkers [35aj. A chiral N-triflyl-phosphoramide 101 was a better selection for the cyclization of dienone substrates 102, and cyclopentenone products 103 were generated as a diastereo-meric mixture but with excellent enantioselectivity at low catalyst loadings (2 mol%) (Scheme 36.27). 

The utility of weak-acidic Bronsted acid catalysts for the Diels-Alder reaction is often limited to reactive substrates. To overcome this drawback, Yamamoto and coworkers designed chiral N-triflyl phosphoramide 74 with higher acidity as catalyst for the enantioselective Diels-Alder reaction of ethyl -vinyl ketone (73) with electron-rich silyloxydiene 72 [32]. Various multifunctional cyclohexenes 75 can be obtained in moderate to excellent yields with high enantioselectivities (Scheme 38.21). 

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