Twibanire Esterification

Twibanire esterification or Twibanire-Grindley esterification is a special type of regioselective esterification between carboxylic acids and alcohols. The reaction was first described by Jean-d'Amour Twibanire and Bruce Grindley in 2011. In this special type of esterification, coupling agents (TBTU, TATU, COMU) are used to promote ester bond formation in the presence of organic bases. When TBTU or TATU are used in the presence of a tertiary amine like N,N-diisopropylethylamine (DIEA) or a weaker organic base, only primary alcohols react to form esters. Under these conditions, secondary or tertiary alcohols do not react.This is extremely important because protecting non-primary hydroxyl groups is not necessary in diols or polyols. This method has been used in the preparation of a library of Lyme Disease Glycolipid Antigens.. For secondary alcohols to react in the presence of TBTU or TATU, a base as strong as 1,8-Diazabicycloundec-7-ene (DBU) has to be used. TBTU and TATU do not promote esterification of tertiary alcohols. Tertiary alcohols react only in the presence of COMU and only when the more stronger base, 1,3,4,6,7,8-Hexahydro-1-methyl-2H-pyrimidopyrimidine is used. Even though ester formation using some coupling agents had previously been reported, the base sensitivity of these reactions which is the source of regioselectivity, was not known until Twibanire and Grindley research work at Dalhousie University.
TBTU: 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate.
TATU: 2-(1H-7-azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate.
COMU: 1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholino-methylene.

Main Menu

See Also

Main Menu