Design chiral phosphoric acids

Chiral phosphoric acids mediate the enantioselective formation of C-C, C-H, C-0, C-N, and C-P bonds. A variety of 1,2-additions and cycloadditions to imines have been reported. Furthermore, the concept of the electrophilic activation of imines by means of phosphates has been extended to other compounds, though only a few examples are known. The scope of phosphoric acid catalysis is broad, but limited to reactive substrates. In contrast, chiral A-triflyl phosphoramides are more acidic and were designed to activate less reactive substrates. Asymmetric formations of C-C, C-H, C-0, as well as C-N bonds have been established. a,P-Unsaturated carbonyl compounds undergo 1,4-additions or cycloadditions in the presence of A-triflyl phosphoramides. Moreover, isolated examples of other substrates can be electrophil-ically activated for a nucleophilic attack. Chiral dicarboxylic acids have also found utility as specific acid catalysts of selected asymmetric transformations. 

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)... 

In 2008, Du and coworkers designed and synthesized novel double axially chiral phosphoric acid catalysts based on BINOL [28]. Subsequently, these catalysts have been successfully applied in asymmetric transfer hydrogenation of 2 substitued (Table 10.8) and 2,3 disubstitued quinolines (Scheme 10.26). They found that ether was the best solvent. For 2 substitued quinolines, up to 98% ee was obtained when the substitutent of catalyst was cyclohexanyl. 

Figure 4.3 Relevant aspects of the design of chiral phosphoric acids as H-donor catalysts.

A number of chiral acid catalysts for the asymmetric AFC reaction of indoles and pyrroles have been reported. However, the less reactive aromatic substrates such as phenols have only been explored with limited success. In this context, Yamamoto s combined acid strategy has been used to design chiral acids with stronger acidity. In a recent work reported by Luo and co-workers, a binary-acid catalytic system consisting of chiral phosphoric acid 13 (Brpnsted acid) and MgFa (Lewis acid) forming multi acidic centers induced... 

The sequential combination of RCM and double-bond isomerization was recently employed by You s group [42] for the design of an RCM-isomerization-Pictet-Spengler cascade for a highly efficient enantioselective synthesis of tetrahydro-P-carbolines 21, where a Hoveyda-Grubbs II complex and a chiral phosphoric acid (CPA-H) cooperatively acted as a bicatalytic system (Scheme 12.13). 

Since the initial reports of Akiyama and Terada [9-12], BlNOL-derived phosphoric acids became very general and popular catalysts. The design of new chiral phosphoric acids has been usually directed to variations of the 3,3 -substituents on the BINOL backbone [16, 37]. We were particularly interested in exploring... 

Our design of a new and extremely sterically demanding Brpnsted acid was based on the analysis of highly successful chiral phosphoric acids [9-12], Wtriflyl phosphoramides introduced by Yamamoto [55] and Wphosphinyl phosphoramides... 

After great success in the reduction of imines, quinolines, and pyridines. Rueping et al. designed a chiral phosphoric acid-catalyzed cascade reaction, in which enamines and enones are heated with Hantzsch ester la and (R)-6, then a Michael addition, cyclization, isomerization and hydride transfer reaction take place successively to afford chiral tetrahydropyridine 59 and azadecaUnone 60 products in excellent enantioselectiYities (Scheme 32.11) [33]. Remarkably,... 

In 2006, Yamamoto and Nakashima picked np on this and designed a chiral A -triflyl phosphoramide as a stronger Brpnsted acid catalyst than the phosphoric acids based on this concept. In their seminal report, they disclosed the preparation of new chiral BINOL-derived A -triflyl phosphoramides and their application to the asymmetric Diels-Alder (DA) reaction of a,p-unsaturated ketones with sily-loxydienes [83], As depicted in Scheme 59, chiral A-triflyl phosphoramides of the general type 4 are readily synthesized from the corresponding optically active 3,3 -substituted BINOL derivatives 142 through a phosphorylation/amidation route. 

Therefore an efficient substrate recognition site could be constructed around the activation site of the phosphoric acid catalyst, namely the acidic proton, as a result of the acid/base dual function and stereoelectronic influence of the substituents (STG). The BINOL derivatives were selected as chiral sources to construct the ring structure The C2 symmetry is crucial in the catalytic design because it means that the same catalyst molecule is generated when the acidic proton migrates to the phosphoryl oxygen. In addition, both enantiomers of the binaphthols are commercially available [52]. 

Replacement of three C-substituents in phosphines by oxy groups produces triesters of phosphorous acid, also called phosphites. Such phosphites play a crucial role as mono- and bidentate ligands, but also as polydentate ligands, in numerous catalytic applications [1]. In Rh-catalyzed hydroformylation, they are indispensable in regioselective transformations at each scale. Several chiral phosphites based on rather complicated alcohols have also been designed for use in asymmetric hydroformylations [2]. 

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]. 

A chiral anion phase-transfer system, provided by the l,l -Bi-2-naphthol(BINOL)-derived phosphoric acids (18), has been designed for the enantioselective halocyclization... 

Recently, chiral bis-phosphoric acid 77 bearing a new chiral scaffold with triple axial chirality assisted by intramolecular hydrogen-bonding between two phosphoric acid moieties was designed as a new chiral Bronsted acid catalyst by the Terada group [33], Application of this catalyst in the Diels-Alder reaction between substituted acroleins 66 and amido-dienes 76 produced the corresponding cycloadducts 78 with excellent enantioselectivities (Scheme 38.22). In comparison with the mono-phosphoric acid, bis-phosphoric acid 77 showed obviously higher catalytic activity and selectivity. 

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