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.