Chiral bis-phosphoric acid

SCHEME 6.13. TADDOL and chiral bis-phosphoric acid catalyzed Diels-Alder reactions of acrolin-derivatives with amidodienes. 

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. 

The catalytic asymmetric /-selective Diels-Alder annulation of a, -unsaturated /-butyrolactams with enones provided a synthesis of, y-functionalized bridged bi-or tri-cyclic dihydropyranopyrrolidin-2-ones in one step (up to 98% yield, >20 1 dr, and 99% ee) The inverse-electron-demand aza-Diels-Alder cycloaddition 0 of A-aryl-a,/0-unsaturated ketimines with enecarbamates in the presence of chiral bifunctional phosphoric acids produced 4,5,6-trisubstituted 1,4,5,6-tetrahydropyridines having three contiguous stereogenic centres in up to 84% yield, 95 5 dr, and 95% 5-Alkenylthiazoles react as in-out dienes with e-poor dienophiles in polar 44-2- 0 cycloaddition reactions. The cycloadditions are site selective. The mechanism is thought to lie between a concerted but highly asynchronous process and a stepwise process. 

This compound, in common with other suitable substituted biphenyls, possesses a chiral axis (p. 6) and is isolated from the reaction as a racemate. Although several resolution procedures have been reported, the superior method to date4 is that in which the binaphthol is first converted by treatment with phosphorus oxychloride into the binaphthyl phosphoric acid (14). Resolution is then effected by formation of diastereoisomeric salts with (+ )-cinchonine, appropriate fractional crystallisation and recovery of the (S)-( + )-binaphthyl phosphoric acid. Suitable hydrolysis gives (S)-( — )-l,l -bi-2-naphthol (15). 

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. 

The chiral catalysts that have been used in nitroaUcene conjugate additions include bw-oxazolines with Cu(OTF)2 [281] or Zn(OTf)2 [282], tridentate bw-oxazolines with Zn(OTf)2 [283], mixed thiazoline-oxazolines with Zn(OTf)2 [284], imidazoUne-aminophenols with CuOTf [285], bis-trifluoromethylsulfonamides [286], binaphthyl sulfonamides [287], binaphthyl imines [288], thioureas [289], and quinoUnyl thioureas [290]. A BINOL-phosphoric acid with 3A molecular sieves gave ee values consistently at 90% and above with both p-alkyl and p-aryl nitroalkenes [291]. 

Inspired by this unique precedent, members of our group used the concept of a chiral phosphoric acid initiator to convert the diol diastereomers of 34 into the quaternary carbon of aldehyde 36, a key precursor toward a total synthesis of the resveratrol dimer hopeanol (37, Scheme l.Bhk The key ideas here hinge upon the ionization ability of the bis-benzylic tertiary alcohol versus the secondary benzylic alcohol affording requisite regiocontrol, while the chiral phosphoric acid could potentially inpart some exogenous stereocontrol to enhance throughput to the desired diastereomer. 

At the same time, Wang and co-workers [60] reported the first examples of enantioselective transfer hydrogenation of unprotected orthohydroxyaryl alkyl N-H ketimines using chiral phosphoric acid as a catalyst and Hantzsch ester as the hydrogen source. The hindered (.S)-3,3 -bis(tilphenylsilyl)-substituted phosphoric acid turned out to be the most effective in terms of chirality transfer, and benzene was a better reaction medium amongst the solvents screened (Scheme 15.27). 

Another important set of bi-component reactions involving C-N and C-C bond formation is based on the Pictet-Spengler reaction, consisting in the cycUzation of electron-rich aromatic moieties onto iminium intermediates. This weU-known sequence constitutes an important domino transformation used for the synthesis of bioactive polyheterocycles. Its organocatalytic asymmetric version was pioneered by Jacobsen and revisited by List, who developed two complementary highly enantioselective accesses to tetrahydro- 3-carbolines from tryptamine-derived imines (Scheme 16.33). Thus, Taylor and Jacobsen [64] reported an enantiomerically pure thiourea-catalyzed cyclization of an acyl iminium intermediate, whereas List and co-workers [65] described the cyclization of an iminium diester intermediate in the presence of a chiral phosphoric acid catalyst. Recently, this methodology has been applied to the synthesis of chiral pyrrolopiperazines [66]. 

The post-synthetic methodology has also been used to incorporate catalytic centres. The incorporation of chiral l,l -bi-2-naphthols (BINOLs) into CMPs has been used to perform catalytic reactions using the alcohol groups to bind to catalytically active centres such as phosphoric acids for asymmetric transfer hydrogenations or titanium for diethyl-zinc additions. Other metal-containing functionalities have also been incorporated into CMP networks. The coordination of metals to pyridine or phenylpyridine via Sonogashira reactions has also been reported for catal5Aic transformations such as reductive amination or aza-Henry reactions, a-atylations and oxyaminations. ... 

Thus, in 2008, List and coworkers published the first enantioselective version of Kabachnik-Fields reaction [214a]. They found that chiral binol-derived phosphoric acids were efficient in inducing chirality under dynamic kinetic resolution conditions when bulky a-branched aldehydes (isopropyl, cyclopentyl and cyclohexyl) were used as substrate in their reaction with p-anisidine and di(3-pentyl) phosphite (Scheme 12.28). In particular, 3,3 -bis(4-anthracenyl-2,6-diisopropylphenyl)-l,l -8-binaphtyl-2, 2 -diyl hydrogenphosphate 80 allowed the synthesis of the corresponding p,p-disubstituted-a-aminophosphonates 84 in high yields with very good stereocontrol (dr up to 28 1 and er up to 97 3). 

Bringing together the concept of aminocatalysis and the activation mode of chiral phosphoric acids. List and co-workers introduced the concept of asymmetric counter anion directed catalysis (ACDC) and they applied this idea to the asymmetric reduction of enals 47 (Scheme 23) [ 135]. The catalytic species is formed by an achiral ammonium ion 60 and a chiral phosphate anion 59 derived from 3,3 -bis(2,4,6-triisopropylphenyl)-1,1 -binaphthyl-2,2 -diyl hydrogen phosphate 9 (TRIP). 

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. ... 

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... 

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