Phosphoric acid catalysts, chiral

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]... 

In 2007, AntiUa and coworkers described the Brpnsted add-catalyzed desymmetrization of me yo-aziridines giving vicinal diamines [75]. hi recent years, chiral phosphoric acids have been widely recognized as powerful catalysts for the activation of imines. However, prior to this work, electrophiles other than imines or related substrates like enecarbamates or enamides have been omitted. In the presence of VAPOL-derived phosphoric acid catalyst (5)-16 (10 mol%) and azidotrimethylsilane as the nucleophile, aziridines 129 were converted into the corresponding ring-opened prodncts 130 in good yields and enantioselectivities (49-97%, 70-95% ee) (Scheme 53). 

Indeed, when we studied various phosphoric acid catalysts for the reductive amination of hydratopicaldehyde (16) with p-anisidine (PMPNH2) in the presence of Hantzsch ester 11 to give amine 17, the observed enantioselectivities and conversions are consistent with a facile in situ racemization of the substrate and a resulting dynamic kinetic resolution (Scheme 16). TRIP (9) once again turned out to be the most effective and enantioselective catalyst for this transformation and provided the chiral amine products with different a-branched aldehydes and amines in high enantioselectivities (Hoffmann et al. 2006). 

The desirable features of phosphoric acids as chiral Bronsted acid catalysts are summarized as follows (Figure 3.1) ... 

Figure 3.1 Chiral phosphoric acids as chiral Bronsted acid catalysts.

In this chapter, we focus on recent achievements in the enantioselective synthesis of chiral amines using 1,1 bi 2 naphthol (BINOL) derived monophosphoric acid (1) or related phosphoric acids as chiral Bronsted acid catalysts 2, 3], The contents are arranged according to the type of bond forming reaction, including carbon carbon, carbon hydrogen, and carbon heteroatom bond forming reactions, followed by specific reaction types. 

Scheme 3.4 Novel structural motifs of chiral phosphoric acid catalysts.

The Friedel Crafts (F C) reaction via activation of electrophiles functionalized by a nitrogen atom, such as imines, is undoubtedly the most practical and atom eco nomical approach to introduce a nitrogen substituted side chain to aromatic com pounds. The enantioselective version of the F C reaction of nitrogen substituted substrates, including imines, with electron rich aromatic compounds enables effi cient access to enantioenriched aryl methanamine derivatives [37[. Several excellent approaches to highly enantioselective F C reactions have been established using chiral phosphoric acid catalysts. 

Shortly thereafter, Zhou and coworkers independently reported the enantioselec tive F C reaction of indoles with a aryl substituted enamides catalyzed by chiral phosphoric acid catalyst lq (Scheme 3.22) [52], in which the quaternary stereogenic center bearing the nitrogen atom vas constructed in a highly enantioselective manner. 

In 2005, Rueping et al. reported that chiral phosphoric acids function as an efficient catalyst for the enantioselective reduction of ketimines (Scheme 3.40a 1) [87]. A variety of aryl methyl ketimines were reduced to the corresponding amines in optically active forms using Hantzsch ester as the hydrogenation transfer reagent (HEH) [88]. Subsequently, List and coworkers improved the catalytic efficiency and enantioselectivity by thorough optimization of the substituents (G) that were introduced to the phosphoric acid catalyst (Scheme 3.40a 2) [89]. Almost simulta neously, MacMillan and coworkers successfully developed the enantioselective... 

Hantzsch ester (2.2 equiv) to give p.y unsaturated a amino esters. Although the chemical yields were moderate, high enantio and trans selectivities were achieved using the same chiral phosphoric acid catalyst Ig. 

Michael addition, geometrical isomerization, cyclization, dehydration, isomeriza tion, and 1,2 hydride addition, in which each single step is efficiently catalyzed by chiral phosphoric acid catalyst Ig. The method enables direct, rapid, and efficient access to a diverse set of tetrahydropyridine and azadecalinone derivatives with excellent enantioselectivities. 

Examining a variety of chiral BINOL based phosphoric acid catalysts in 2005, List found TRIP (Scheme 7.4) to be optimal (1.0mol%) for the catalytic protonation of preformed imines of p anisidine [15]. 

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. 

A related reaction involves the use of aryl indole-3-carbinols with enamides. Under the influence of acid catalysts the carbinols generate electrophiles. The adducts hydrolyze to products that are the equivalent of conjugate addition to 1,3-diaryl propenones. These reactions can be done in up to 90% ee with chiral BINOL-phosphoric acid catalysts [293]. 

Efficient access to biologically and pharmaceutically interesting hydroxy-oc-amino acids derivatives (145) having a quaternary stereogenic center at the a-carbon atom, through the direct aldol-type reaction of azalactone (144) with an oxocarbenium ion obtained via protonation of vinyl ethers (143), by a chiral phosphoric acid catalyst (127) in a highly enantio- and diastereoselective manner, have been developed by Terada and co-workers (Scheme 38). ... 

Binaphthol-derived chiral phosphoric acid catalysts (137 or 157-162) have been applied to enantioselective radical addition reactions of alkyl iodides to imines (155) and provided chiral amines (156) in good enan-tioselectivities (73-84% ee) (Scheme 42). " ... 

There is also one example in which a chiral phosphoric acid has been employed as catalyst in the reaction. In particular, the addition of several cyclic p-ketoesters to methyl vinyl ketone was found to occur smoothly in the presence of several chiral phosphoric acids (Scheme 4.35). As mentioned earlier, a key feature of the chiral phosphoric acid catalyst is the backbone binaphthyl axial chirality together with the incorporation of bulky substituents at the 2 positions. In this case, 60b was identified as an appropriate promoter of the reaction leading to the corresponding Michael adducts in excellent yields, although with moderate enantioselectivity. In addition, the authors succeeded in applying this reaction to a procedure to carry out a subsequent Robinson-type annulation. 

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