TY - JOUR

T1 - Taming of the DIBAL Promoted Debenzylation of α-Cyclodextrin. Kinetics, Substituent Effects and Efficient Synthesis of Lings Tetrol**

AU - Bols, Mikael

AU - Friis, Victor

N1 - Funding Information: 800 MHz NMR data was recorded at cOpenNMR an infrastructure facility funded by the Novo Nordisk Foundation (#NNF18OC0032996). Publisher Copyright: © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

PY - 2022

Y1 - 2022

N2 - 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 1st 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 3A,6A,6D-triol (Lings triol) were both found to be 1st 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,3A,6A,6D-tetrol and the 3A,6A,6C,6D-tetrol. In contrast reaction at 0.1 M DIBAL gave the symmetrical 3A,6A,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 6A,6D-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 6A,6D-diol product.

AB - 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 1st 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 3A,6A,6D-triol (Lings triol) were both found to be 1st 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,3A,6A,6D-tetrol and the 3A,6A,6C,6D-tetrol. In contrast reaction at 0.1 M DIBAL gave the symmetrical 3A,6A,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 6A,6D-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 6A,6D-diol product.

KW - aluminium hydrides

KW - benzyl groups

KW - cyclodextrin

KW - kinetics

KW - substituent effects

U2 - 10.1002/chem.202200564

DO - 10.1002/chem.202200564

M3 - Journal article

C2 - 35384086

AN - SCOPUS:85127785671

VL - 28

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 29

M1 - e202200564

ER -