Phosphoric acid catalysis, chiral

Keywords Asymmetric catalysis BINOL Dicarboxylic acids A-Triflyl phosphoramides Phosphoric acids Strong chiral Brpnsted 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)... 

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... 

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

Asymmetric binary acid catalysis Chiral phosphoric acid as dual hgand and acid 13CC847. 

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... 

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.

Scheme 7.58 Tandem isomerisation-aza-Petasis-Ferrier rearrangement reaction catalysed by nickel catalysis and chiral phosphoric acid catalysis followed by reduction.

Scheme 7.60 Tandem cycloisomerisation-condensation-q clisation reaction catalysed by gold catalysis and chiral phosphoric acid catalysis.

A reasonable place to start would be to use a combination of Selectfluor and a chiral phosphoric acid catalyst (chiral anion phase-transfer catalysis) [20]... 

Since the seminal reports from the Akiyama group [62] and the Terada group [63] in 2004, chiral phosphoric acid catalysis has become a very exciting field in the past few years [64-66]. Our group has made some efforts to increase the acidity of this type of catalysts through modifying chiral phosphoric acid structure to corresponding chiral W-triflyl phosphoramide [67, 68] or W-triflyl thio- and... 

Much of this introductory section is taken from our review on the same subject that appeared in the earher edition of this volume [1]. Chiral phosphoric acids and chiral thioureas, each representing a major subdivision of hydrogen bonding catalysis, are discussed in separate chapters, the former by Professor Aldyama (Chapter 11) and the latter by Professor Schreiner (Chapter 12). 

I 77 Br0nsted Acids Chiral Phosphoric Acid Catalysis in Asymmetric Synthesis... 

The actual catalyst in phosphoric acid-catalyzed Mannich-type reaction of imines with 1,3-dicarbonyl compounds is certainly phosphoric acid itself [74], but metal contaminants, such as alkali or alkaline-earth metals, have interesting effects on the reactivity and stereoselectivity. HCl-washed, metal-free chiral phosphoric acid 149a and chiral calcium phosphate 149b are able to catalyze the Mannich-type reactions. The absolute stereoselectivity of the phosphoric acid catalysis is opposite that of the calcium phosphate catalysis (Scheme 28.16) [75]. 

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