Tryptophan-derived chiral catalysts

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

Since our group (22) and Hehnchen s (23) independently announced a new class of chiral acyloxyboranes derive from iV-sulfonylamino acids and borane THF, chiral 1,3 -oxazaborolidines, their utility as chiral Lewis acid catalysts in enantioselective synthesis has been convincingly demonstrated (2(5). In particular, Corey s tryptophan-derived chiral oxazaborolidines 10a and 10b are highly effective for not only Mukaiyama aldol reactions (24) but also Diels-Alder reactions (25). More than 20 mol% of 10b is required for the former reaction, however. Actually, the reaction of the trimethylsilyl enol ether derived from cyclopentanone with benzaldehyde afforded the aldoI products in only 71% yield even in the presence of 40 mol%of 10b (24). We recently succeed in renewing 10b as a new and extremely active catalyst lOd using arylboron dichlorides as Lewis acid components (2(5). 

A series of chiral boron catalysts prepared from, e.g., N-sulfonyl a-amino acids has also been developed and used in a variety of cycloaddition reactions [18]. Corey et al. have applied the chiral (S)-tryptophan-derived oxazaborolidine-boron catalyst 11 and used it for the conversion of, e.g., benzaldehyde la to the cycloaddition product 3a by reaction with Danishefsky s diene 2a [18h]. This reaction la affords mainly the Mukaiyama aldol product 10, which, after isolation, was converted to 3a by treatment with TFA (Scheme 4.11). It was observed that no cycloaddition product was produced in the initial step, providing evidence for the two-step process. 

The chiral oxazaborolidines introduced in Section 2.1.3.5 as enantioselective aldol addition catalysts have also been found to be useful in Diels-Alder reactions. The tryptophan-derived catalyst A, for example, can achieve 99% enantioselectivity in the Diels-Alder reaction between 5-benzyloxymethyl-l,3-cyclopentadiene and 2-bromopro-penal. The adduct is an important intermediate in the synthesis of prostaglandins.64... 

Novel bidentate chiral Lewis acids derived from 1.8-naphthalenediylbis(dichloroborane) and modified amino acids as chiral auxiliary have been successfully utilized as effective catalysts for the asymmetric Diels-Alder reaction of a,[ -unsaturated aldehydes. The enantioselectivity is highly sensitive to the kind of chiral amino acids. Moderate enantioselectivity was obtained with the tryptophan-derived ligand for the endo adduct, but amino acids without aromatic groups... 

The iminium activation strategy with the trifunctional chiral primary amine 28, which was used in the y-selective conjugate addition of y-butenolides (Scheme 28), also proved highly effective for promoting reaction with the y-butyrolactam (Scheme 32, first line) [52]. Although various chiral diamines, amino thioureas, and amino sulfonamides were evaluated during the optimization study, none of these catalysts gave rise to impressive levels of diastereoselectivity. Eventually, a bulky acid additive, such as the protected tryptophan derivative (V-Boc-L-Trp-OH),... 

Among nonmetal chiral complexes, chiral oxazaborolidines have been found effective in many D-A reactions. The adduct obtained from the D-A reactions of 5-benzyloxymethyl-l,3-cyclopentadiene 98a with a-bromoacrolein in the presence of catalyst 98 (S-tryptophan-derived oxazaboroUdine) is an important intermediate in the synthesis of prostaglandins. The aldehyde group of the dienophile is bound to the catalyst by coordination with boron by Lewis interaction and the Lewis complex is stabilized by H-bonding. The upper face of the aldehyde is shielded by indole moiety of the catalyst. The benzyloxymethyl substituent of the cyclopentadiene produces a steric differentiation on the two faces of cyclopentadiene ring resulting the approach of the diene preferably from one face. 

However, when this approach was applied to dehydro-pentagastrin (Boc-/3Ala-A -Trp-Met-Asp-Phe-NH2) it became evident that the structure of the catalyst was not the only factor influencing the stereoselectivity of the reaction. Achiral hydrogenation conditions (PdO) led to a 52% diastereomeric excess in favor of the (R)-tryptophan derivative. Asymmetric induction was also very low in the presence of chiral rhodium catalysts 44% in favor of the (/f)-diastereomer with [Rh-(S,S)-DIOP](DIOP = 2,3-C>-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane) and only 26% in favor of the (5)-diastereo-mer with [Rh-(/ ,i )-DIPAMP] + BF4. ... 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

CAB 3c derived from N-tosyl (a5 / )-/3-methyltryptophan catalyzes the Diels-Alder reaction of 2-bromoacrolein and furan with 96 4 enantioselectivity, enabling efficient synthesis of numerous chiral 7-oxabicyclo[2.2.1]heptene derivatives (Eq. 17) [18]. Interestingly, the analog 3b of catalyst 3c which lacks the y8-methyl group (derived from M-tosyl-(5)-tryptophan) is not as effective at catalyzing the formation of Diels-Alder product, and the reaction rate and yield are considerably lower. 

In recent years, catalytic asymmetric Mukaiyama aldol reactions have emerged as one of the most important C—C bond-forming reactions [35]. Among the various types of chiral Lewis acid catalysts used for the Mukaiyama aldol reactions, chirally modified boron derived from N-sulfonyl-fS)-tryptophan was effective for the reaction between aldehyde and silyl enol ether [36, 37]. By using polymer-supported N-sulfonyl-fS)-tryptophan synthesized by polymerization of the chiral monomer, the polymeric version of Yamamoto s oxazaborohdinone catalyst was prepared by treatment with 3,5-bis(trifluoromethyl)phenyl boron dichloride ]38]. The polymeric chiral Lewis acid catalyst 55 worked well in the asymmetric aldol reaction of benzaldehyde with silyl enol ether derived from acetophenone to give [i-hydroxyketone with up to 95% ee, as shown in Scheme 3.16. In addition to the Mukaiyama aldol reaction, a Mannich-type reaction and an allylation reaction of imine 58 were also asymmetrically catalyzed by the same polymeric catalyst ]38]. 

Chiral boranes have been recommended as Lewis acids catalysts by Reetz [689], Yamamoto [787, 788], Kiyooka [795, 1302], Masamune and their coworicers [796, 797], These groups used, respectively, boranes 2.61, 3.9 (R = H, R = /-Pr), 3.10 (R = i-Pr or tert-Bu, R = H) and derivatives of 3.12 and 3.13. These boranes are very efficient catalysts in asymmetric additions of symmetrically substituted ketene silylacetals 6.113 to aldehydes (Figure 6.94). Similar reactions can also be conducted with enoxysilanes derived from methylketones or from tert-Bu thiolacetate [787, 794, 796], Oxazaborolidine 3.10 derived from tryptophan 3.11 is also a very potent catalyst [794],... 

Previously, Ascic et al. [43] reported the same reaction with the Hoveyda-Grubbs II catalyst and trifluoroacetic acid as a bicatalytic system, but as a racemic version [43]. The intermediate acyliminium ion readily attacks also other tethered nucleophiles, such as trimethoxybenzene, benzothiophene, thiophene, 0,0-dimethyl catechol, and furan, intramolecularly. When tryptophane or the corresponding alanine derivatives are employed, reasonable levels of diastere-oselectivity can be observed for the terminal Pictet-Spengler acyhminium cyclization. Even a tethered alcohol functionahty diastereoselectively traps the chiral acyhminium intermediate, furnishing bicychc OAf-acetals. 

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