BINOL derivatives bifunctional catalysts

Chiral Binol-Derived Bifunctional Amine Catalysts... 

As for organoaluminum species containing Al-bonded heteroatoms, research into alkoxides and aryloxides is well established. Nevertheless, the advent of BINOL-derived bifunctional chiral Al(III) complexes has already enabled the design and synthesis of a broad range of asymmetric catalysts. Bifunctional catalysts of this type - susceptible to interact both with electrophiles and nucleophiles and so to potentially achieve spectacular stereodiscrimination - will undoubtedly lead to interesting future developments. 

In related work, Sasai developed several bifunctional BINOL-derived catalysts for the aza-Morita-Baylis-Hillman (aza-MBH) reaction [111]. In early studies, careful optimization of the catalyst structure regarding the location of the Lewis base unit revealed 41 as an optimal catalyst for the aza-MBH reaction between acyclic a,P-unsaturated ketones and N-tosyl imines. Systematic protection or modification of each basic and acidic moiety of 41 revealed that all four heterofunctionalities were necessary to maintain both chemical and optical yields. As seen in Scheme 5.58, MO calculations suggest that one hydroxyl groups forms a... 

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

The great versatility of binol as a chiral ligand has been extended to the Strecker reaction. Shibasaki38 has developed bifunctional catalysts employing the use of this species. After the reportewd use of an aluminum variation of this catalyst 75 for the asymmetric formation of cyanohydrins, aluminum and gadolinium derivatives of 78 were shown to efficiently catalyze the addition of cyanide to imines. 

The bifunctional catalysts developed by Shibasaki and coworkers effective in the asymmetric cyanation of aldehydes and ketones (see Section 6.2) have been applied to good effect in the cyanation of imines. For instance, aluminium BINOL (6.65) catalyses the cyanation of aromatic and a,p-unsaturated N-fluorenylaldimines using TMSCN in good ee, while gadolinium complexes of the glucose-derived ligand (6.71) and derivatives have been used in the enantioselective cyanation of ketimines. ... 

In 2003, we first demonstrated that l,l -bi-2,2 -naphthol (BINOL)-derived chiral LBBA (Lewis base and Bronsted add) bifunctional phosphine CP17 (LB = PPhs, BA = Ph-OH) could be used as an effective catalyst in asymmetric aza-MBH reaction of A-tosylimines with MVK and phenyl acrylate, affording the corresponding adducts in good yields with high ees (Scheme 2.119). The addition of molecular sieves increased chemical yields because they removed the ambient moisture that caused the decomposition of A-sulfonated imines. The asymmetric induction of this catalyst is comparable to that of the quinidine... 

Asymmetric addition of diorganozincs to aldehydes and ketones has been reviewed, focusing on bifunctional catalysts such as those prepared from salens or BINOLs. Regioisomeric chiral amine-sulfonamide organocatalysts give >99% yield and up to 98% ee in addition of diethylzinc to aldehydes. Switching between regioisomers effectively switches the direction of selectivity. Amino-acid-derived (15,l 5)-4,4 -biquinazoline primary amines catalyse ethylation of aryl aldehydes in up to 95%... 

For example, Sasai and coworkers reported the metal-free bifunctional Binol derivative 67 as an effective catalyst for an enantio-selective aza MBH reaction. " In the presence of 10 mol% of 67, methyl vinyl ketone and a series of tosylamines 66a-e were converted to adducts 68a-e in high yields with 88-95% ee. It has been rationalized that both the 2-hydroxy and pyridine moieties of 67 contributed to this highly enantioselective transformation. 

In 2003, Rawal reported the use of TADDOLs 177 as chiral H-bonding catalysts to facilitate highly enantioselec-tive hetero-Diels-Alder reactions between dienes 181 and different aldehydes 86 (Scheme 6.29A) [82], and also BINOL-based catalysts 178 were found to facilitate this reaction with excellent selectivities [83]. TADDOLs were also successfully used as organocatalysts for other asymmetric transformations like Mukaiyama aldol reactions, nitroso aldol reactions, or Strecker reactions to mention a few examples only [84]. In addition, also BINOL derivatives have been employed as efficient chiral H-bonding activators as exemplified in the Morita-Baylis-Hilhnan reaction of enone 184 with different carbaldehydes 86 [85]. The use of chiral squaramides for asymmetric reactions dates back to 2005 when Xie et al. first used camphor-derived squaric amino alcohols as ligands in borane reductions [86]. The first truly organocatalytic application was described by Rawal et al. in 2008 who found that minute amounts of the bifunctional cinchona alkaloid-based squaramide 180 are... 

Other successful asymmetric organocatalytic cycloadditions were developed in the last year, such as a three-component asymmetric 1,3-dipolar cycloaddition between aldehydes, amino esters and dipolarophiles, which was catalysed by a new biphosphoric acid derived from (i ,/ )-linked BINOL, furnishing multiply substituted pyrrolidines in high yields and with exeellent enantioselectivities of up to 99% ee. In addition, a new class of chiral bifunctional thiourea catalysts derived from traTO-2-amino-l-(diphenylphosphino)cyclohexane was applied to a highly enantioselective synthesis of a wide range of 2-aryl-2,5-dihydropyrrole derivatives on the basis of a [3 -b 2] cycloaddition between an A-phosphinoyl imine and an allene, providing high yields combined with excellent enantioselectivities of up to 98%. 

Shibasaki and Kanai have also reported bifunctional asymmetric catalyst (66) derived from carbohydrates (Scheme 6.47) [61]. Compared to BINOLate type catalyst (64a), generally, the enantiomeric excess values of resultant cyanohydrin silyl ethers were not higher. The reaction proceeded with high enantiomeric excess without both slow addition of TMSCN and the use of external phosphine oxide as an additive. 

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