Hydroxy acids TADDOL

Momiyama and Yamamoto" have further expanded the utility of H-bond-mediated reactions catalyzing nitrosobenzene addition to enamines using TADDOL 38 or hydroxy acid 39 as catalysts. Remarkably, the judicious selection of H-bond-catalyst/enamine combination resulted in the formation of only A-addition compounds with TADDOL 38 (Scheme 11.14e), while acid 39 furnished exclusively O-nitroso aldol products (Scheme 11.14f). 

Upon formation of the trans adduct of benzaldehyde with TADDOL, the mframolecular hydrogen bond is shortened by 0.128 A, and the acidity of the substrate binding hydroxy function is increased. The length of the intermolccular hydrogen bond to the carbonyl group is 1.825 A. 

A related approach has recently been reported by Belokon and Kagan et al. These workers used chiral TADDOL-type diols, derived from tartaric acid and 2-amino-2 -hydroxy-1,1 -binaphthyl (NOBIN), as catalysts to obtain yields of up to 95% and enantioselectivity up to 93% ee [59-61], The catalytically active species seem to be the sodium salts of the diols. 

Romo et al. have used Lewis acids to catalyze the formation of a-silyl-/ -lactones in their synthesis of potential inhibitors of yeast 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) synthase <1998BMC1255>. In addition to various Lewis acid catalysts, a chiral promoter based on the chiral diol (l/ ,2R)-2-[(diphenyl)hydroxymethyl]cyclo-hexan-l-ol was introduced to the reaction in an attempt to improve the stereoselectivity. A variety of chiral 2-oxetanones were formed, with enantioselectivities ranging from 22% to 85%. Dichlorotitanium-TADDOL catalysts 113 and 114 have also been used in an attempt to encourage the stereoselective [2+2] cycloaddition of silyl ketenes and aldehydes (TADDOL = (—)-/ra r-4,5-bis(diphenyl-hydroxymethyl)-2,2-dimethyl-l,3-dioxolane), although this method only afforded 2-oxetanones in moderate yields and optical purity (Equation 41) <1998TL2877>. 

Other Enantioselective Transformations Mediated by Ti-TADDOLates. The iodolactonization of 2-allyl-2-hydroxy-4-pentenoic acid shown in eq 8 gives (21) in a 67% yield (after cyclization of some iodo isopropyl ester formed as a side product), the iodolactone is a single (—)-diastereoisomer with a 5 1 (S,S)I(R,R) ratio. The TADDOLate generated in situ was employed in stoichiometric amount. The two enantiomers of 2-pyridyl 2-phenylthiobutyrate react with a rate difference of 39 1 with excess isopropanol in the presence of 0.1 equiv of a Ti-TADDOLate under the conditions specified in eq 9. This leads to the isopropyl ester (22) containing 96% of the (/ )-enantiomer... 

In 2002, Huang and Rawal found that the hetero Diels-Alder reaction of aminosiloxydienes with aldehydes was accelerated in alcoholic solvents [65], They subsequently elucidated that TADDOL (19) is an efficient chiral catalyst for the hetero-Diels-Alder reaction (Figure 10.17, Equation 10.33) [66]. The internal hydrogen bond in TADDOL observed in its crystal structure is expected to render the hydroxy proton more acidic, hence enabling it to participate better in intermolecular hydrogen bonding with the carbonyl group of the dienophile [67]. The Mukaiyama aldol reaction was also reported [68]. 

Porco et al. reported the synthesis of ( ) methyl rocaglate using [3 + 2] dipolar photocycloaddition reaction of an oxidopyrylium betaine derived from excited state intramolecular proton transfer reaction of 3-hydroxyflavin and methyl cinnamate [144]. Methyl rocaglate was obtained by a base-mediated a-ketol rearrangement followed by hydroxy-directed reduction sequence. They subsequently succeeded in the asymmetric synthesis of methyl rocaglate using functionalized TADDOL derivative (34) (Figure 2.30) as a chiral Bronsted acid (Scheme 2.77) [145]. 

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