Enol, enantioselective tautomerization

The enol formed by irradiation of a-disubstituted indanones and tetralones bearing at least one hydrogen in the y-position undergoes enantioselective tautomerization to ketone in the presence of catalytic amounts of optically active aminoalcohols [74]. 

Duhamel et al. [29] reported the conjugated addition of thiobenzoic add to 2-benzyl acroleine 58f resulting in the formation of a metastable enol 63 with high Z/E selectivity (Z/E >95%). Subsequent enantioselective tautomerization of 63 was achieved in the presence of a chiral protonating agent. By conducting the tautomerization in the presence of 1 eq of (-)-A -methyl ephedrine 64, the desired aldehyde 601 was obtained in 58% ee, while the enantioselectivity could be raised to 71% ee by using cinchonidine 7 as chiral inductor (Scheme 3.34). 

Another approach for the synthesis of enantiopure amino acids or amino alcohols is the enantioselective enzyme-catalyzed hydrolysis of hydantoins. As discussed above, hydantoins are very easily racemized in weak alkaline solutions via keto enol tautomerism. Sugai et al. have reported the DKR of the hydantoin prepared from DL-phenylalanine. DKR took place smoothly by the use of D-hydantoinase at a pH of 9 employing a borate buffer (Figure 4.17) [42]. 

The Muzart group reported an organocatalytic protonation reaction based on an in situ-formation of the required enolate by photochemical tautomerization of the chiral ammonium enolate 26 as an initial step [21]. The ammonium ion in 26 functions as the chiral proton source. Subsequent esterification affords the desired car-boxylate 20 in up to 65% yield and enantioselectivity in the range 40-85% ee. An example is shown in Scheme 9.8. The best results were obtained by use of the secondary, N-isopropyl-substituted aminobornanol for formation of the chiral ammo-... 

Obviously optically active furanones are equilibrated by keto-enol tautomerism in acidic media. Thus, enantioselective analysis cannot be applied to assign the origin of chiral 3 [2H]-furanones [62]. This can only be expected by stable isotope measurements [104, 105]. 

The Scheidt group reported a highly diastereo- and enantioselective NHC-catalyzed reaction of a,p-unsaturated aldehydes with nitrones to afford y-amino esters. It is postulated that a rare six-membered heterocycle is generated as the initial product of the reaction, which gives the final y-amino ester product upon the addition of an alcohol. The mechanism for this reaction involves the addition of the homoenolate equivalent to the nitrone as the stereochemical-determining step, and catalyst turnover is promoted by an intramolecular acylation after the tautomerization of enol to acyl azolium (Scheme 7.60). 

The Bode group disclosed NHC-catalyzed highly enantioselective annulations of a,P,P -trisubstituted enals with cyclic sulfonylimines. Mechanistically, it is proposed that the combination of enal and free NHC leads to the formation of the Breslow intermediate, which is oxidized to form the key a,p-unsaturated acyl azolium. Tautomerization between the imine and the enamine occurs readily in the presence of base, and the enamine is intercepted by the key a,p-unsaturated acyl azolium to form a hemiaminal which further engages in a Stork-Hickmott-Stille-type annulation via a tight-ion-pair/aza-Claisen type transition state. Lactam formation follows the protonation of enolate and brings about catalyst turnover to complete the catalytic cycle (Scheme 7.113). 

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