A Bee-line Approach to Access Organocatalysts: A Suitable Base Catalyzed, Time-dependent, Chemoselective O-functionalization of Prolinol

Herein a successful chemoselective either functionalization of the nucleophilic sites of prolinol by exploiting the relative acidity difference and inverted nucleophilicity of the corresponding conjugate bases, employing a suitable base is reported. An elaborate investigation into the overlooked sensitivity of reaction conditions to a highly utilized protocol has been reported. As an example, mono-Boc functionalization of prolinol for the exclusive synthesis of either NBoc/OBoc/Oxazolidinone derivatives is reported. 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 recognize 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 applicable as suitable catalysts in asymmetric reactions. Never-reported-before substrates such as O-Boc, O-CBz, O-Bz and O-ethyl carbonate derivatives of prolinol were synthesized in good to excellent yields along with other substrates.