Phosphoric acids catalysis

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. 

Although phosphoric acids have found broad applicability for a wide range of asymmetric transformations, most reactions are limited to electrophilic activation of imines. Expanding the scope of phosphoric acid catalysis to other classes of electrophiles, Akiyama and Terada subsequently reported activation of nitroalkene [38] and carbonyl [39] electrophiles, respectively (Scheme 5.23). 

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)... 

Fig. 6.11 Akiyama s two-point binding model for phosphoric acid catalysis.

Scheme 11. Phosphoric acid catalysis pioneered by Akiyama and Terada...

Soon after these initial reports, the groups of Antilla [92] and You [93] indepen dently applied the chiral phosphoric acid catalysis to the enantioselective hydro genation of a imino esters. The method provides an alternative route to the enantioselective synthesis of a amino esters. Antilla and coworkers employed a new type of axially chiral phosphoric acid (9) derived from VAPOL originally developed by his research group (Scheme 3.42), whereas lg was used in You s case. In both cases, excellent enantioselectivities were achieved. You and coworkers further applied the method to the enantioselective reduction of a imino esters having an alkynyl substituent at the a position (Scheme 3.43) [94]. Both alkyne and imine moieties were reduced under transfer hydrogenation conditions with an excess amount of... 

The Pictet-Spengler reaction is important for the preparation of tetrahydro-(3-carbolines and tetrahydroquinolines. List and co-workers applied phosphoric acid catalysis to the Pictet-Spengler reaction starting from geminally disubstituted tryptamines (Equation 10.41) [85, 86], The presence of the bis(ethoxycarbonyl) group facilitated the cyclization reactions by virtue of the Thorpe-Ingold effect. Both aliphatic and aromatic aldehydes turned out to be good substrates. 

Table 6.5 Au and chiral phosphoric acid catalysis cascade reported by Dixon.

FIGURE 2.36. The Simon-Goodman transition state working models for the binol-derived phosphoric acid catalysis of nucleophilic additions to imines. 

One important breakthrough in the field was achieved by Li and AntUla in 2009 [61], when they reported the asymmetric hydrogenation of enamides with high enantioselectivity through the employment of chiral phosphoric acid catalysis (Scheme 15.28). Starting from the assumption that a reactive iminium was the intermediate of this reaction, the authors followed the catalytic strategy to pair the phosphoric acid with a suitable achiral acid, to facilitate iminium formation while... 

V quez, P.G., Blanco, M.N., Caceres, C.V. 1999. Catalysts based on supported 12-molybdo-phosphoric acid. Catalysis Letters 60(4) 205-215. 

SCHEME 2.17 Axially chiral phosphoric acid catalysis of vinylogous Mannich reaction. 

Based on previous studies where the imines were reduced with Hantzsch dihydropyridines in the presence of achiral Lewis [43] or Brpnsted acid catalysts, [44] joined to the capacity of phosphoric acids to activate imines (for reviews about chiral phosphoric acid catalysis, see [45-58]), the authors proposed a reasonable catalytic cycle to explain the course of the reaction (Scheme 3) [41]. A first protonation of the ketimine with the chiral Brpnsted acid catalyst would initiate the cycle. The resulting chiral iminium ion pair A would react with the Hantzsch ester lb giving an enantiomerically enriched amine product and the protonated pyridine salt B (Scheme 3). The catalyst is finally recovered and the byproduct 11 is obtained in the last step. Later, other research groups also supported this mechanism (for mechanistic studies of this reaction, see [59-61]). 

Indole 7 was enantioselectively alkylated by nitrostyrene 8 applying chiral phosphoric acid catalysis (Scheme 3.4). The highest enantioselectivity of the product 9 was obtained when the bis-TMS substituted phosphoric acid was applied. ... 

Scheme 7.1 Passerini-type reaction catalysed by chiral phosphoric acid catalysis and aluminium catalysis.

Scheme 7.24 Three-component reaction of aiyl diazoacetate with alcohol, aldehyde and amine catalysed hy chiral phosphoric acid catalysis and rhodium catalysis.

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