Cyclodextrin regioselective hydrolysis

Isoxazolines 38 and 39 were obtained in different ratios by direct cycloaddition of 4-t-butylbenzonitrile oxide with acids 35 (R = H, path B) and by the intermediate formation of cyclodextrin derivatives 36 and 37 followed by basic hydrolysis and acidification (path A). The reversed regioselectivity as well as an increased rate of the cycloaddition step could be explained through the temporary association of the nitrile oxide with the cyclodextrin to give the inclusion complex 40 <06CEJ8571>. 

Regioselective reaction of phenols. Reaction of phenols with chloroform in aqueous alkaline solution catalyzed by P-cyclodextrin results in virtually complete attack at the para-position by dichlorocarbene to give, after hydrolysis, 4-hydroxybenzaldehydes. If the para-position is substituted, 4-(dichloromethyl)-2,5-cyclohexadienones are obtained as the major product. The selectivity results from formation of a ternary complex from P-cyclodextrin, chloroform, and the phenol. ... 

A different kind of selectivity has been observed with cyclodextrin bisimidazoles. These species were synthesized as mimics of the enzyme ribonuclease, and indeed they do perform the cleavage of certain bound phosphate esters with a mechanism closely related to that of the natural enzyme [26]. Of course in the natural enzyme there is considerable selectivity, including regioselectivity. For instance, the natural enzyme can cleave a cyclic phosphate ester between C-2 and C-3 of a ribose unit in such a way as to leave the phosphate group entirely on C-3. Ordinary chemical hydrolysis of such a molecule would lead to a mixture of C-2 and C-3 phosphates. Our cyclodextrin bisimidazole is able to imitate such selectivity. 

With acrylic acids, a remarkable reversal of regioselectivity is observed when the dipolarophile is attached to fS-cyclodextrin [325]. For instance, the direct cycloaddition of (4-tert-butyl)benzonitrile oxide (8) to acrylic acid gives rise to the isoxazoUnes (9/10) in a ratio of 20 1 in favor of the 3,5-disubstituted product 9. However, when acrylic acid esterified with the OH-group at the -position of fi-cydodextrin is reacted with 8, the isoxazoUnes (9/10) are obtained in a ratio of 1 20 in favor of the 3,4-disubstituted product 10 after removal of the cydodextrin by alkaUne hydrolysis. The reversed regioselectivity... 

---