Unprecedented Chemoselective O-functionalization of Prolinol: An Unmediated Approach to Access Organocatalysts

Abstract

Herein, a successful chemo-selective either functionalisation of the nucleophilic sites of prolinol by exploiting the relative acidity difference and inverted nucleophilicity of the corresponding conjugate bases with a suitable base is reported. As an example, mono-Boc functionalisation of prolinol for the exclusive synthesis of either NBoc/OBoc/Oxazolidinone derivatives is reported. Never-reported-before O-Boc prolinol has been synthesized in 85% yield and other known derivatives (NBoc and oxazolidinone derivatives) have been synthesized in good to excellent yields. Failing to emulate the former protocols, a mechanistic investigation was initiated which revealed that the rudimentary steps can be controlled by: a) A requisite base to distinguish the differently acidic sites (NH and OH) for the formation of the conjugate base reacting to the electrophile, b) The disparity in nucleophilicity of the completely formed conjugate basic sites. This protocol has been extended to be successful with various other substrates which might prove to be applicatory as suitable catalysts in asymmetric reactions