Taming of the DIBAL Promoted Debenzylation of α‐Cyclodextrin. Kinetics, Substituent Effects and Efficient Synthesis of Lings Tetrol

The kinetics of the reaction of perbenzyl α‐cyclodextrin was studied varying the concentration of DIBAL and substrate, and the temperature. The initial debenzylation was found to be 1(st) order in substrate and follow the relationship 0.0675+0.179[DIBAL](2) with respect to the concentration of DIBAL. The second and the third debenzylation which led to the 3(A),6(A),6(D)‐triol (Lings triol) were both found to be 1(st) order in substrate concentration and zero order in DIBAL concentration. Longer reaction times with DIBAL in high concentration gave further debenzylation to comparatively complex mixtures containing the 2B,3(A),6(A),6(D)‐tetrol and the 3(A),6(A),6(C),6(D)‐tetrol. In contrast reaction at 0.1 M DIBAL gave the symmetrical 3(A),6(A),3D,6D‐tetrol (Lings tetrol) in 60 % yield. The effect of chlorine or methyl substitution of the phenyl groups of perbenzyl α‐cyclodextrin was also investigated. Per 4‐chlorobenzyl slowed down the reaction with DIBAL, while 4‐methylbenzyl increased the reaction rate, but still gave the corresponding 6 A‐monool or 6(A),6(D)‐diol products. A Hammett reaction constant of −4.9 was found for the first debenzylation showing a high degree of positive charge in the transition state. The per(2,4‐dichlorobenzyl)‐α‐cyclodextrin‐derivative was completely resistant to DIBAL, however upon addition of trimethyl aluminium this derivative also reacted to give the 6(A),6(D)‐diol product.