A colourful azulene-based protecting group for carboxylic acids

作者：Bevan Thomas W; Francis Taylor James; Wong Helena; Northcote Peter T; Harvey Joanne E^*

来源：Tetrahedron, 2018, 74(24): 2942-2955.

DOI：10.1016/j.tet.2018.04.066

• Azulene derivative
• 6-(2-hydroxyethyl)azulene
• Protecting group
• Carboxylic acid
• Basic deprotection

An intensely blue-coloured protecting group for carboxylic acids has been developed. The protecting group is introduced through a Steglich esterification that couples 6-(2-hydroxyethyl)azulene (AzulE) and the carboxylic acid substrate. Deprotection is effected under basic conditions by the addition of the amidine base DBU, whereupon cleavage occurs, accompanied by a colour change. A two-step deprotection methodology comprising activation with oxalyl chloride and deprotection with a very mild base was developed for use with base-sensitive substrates. The AzulE esters were found to be compatible with other commonly employed protecting groups - silyl ethers, MOM acetals - by studying their orthogonal and concomitant deprotections. The stability of the new protecting group towards various synthetic processes - oxidation, reduction, cross-coupling, olefination and treatment with base - provided the basis of a versatility profile. This indicated that AzulE esters are sensitive to strongly oxidising and basic agents while being compatible with reducing conditions and selected other reactions. The convenience of a highly coloured protecting group for tracking material (and avoiding loss of compound) through laboratory processes warrants further investigation of this and/or related species.

• 出版日期2018-6-14