Affiliation:
1. Center for Analysis and Synthesis Department of Chemistry Lund University Box 124 22100 Lund Sweden
2. Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province Shantou University Shantou Guangdong 515063 P.R. China
Abstract
AbstractWe have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2‐diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this reaction; (ii) a novel and straightforward protocol for the “click‐type” synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1′‐(1‐(4‐fluorophenyl)ethane‐1,2‐diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the enantioselectivities of the reaction.
Subject
General Chemistry,Catalysis,Organic Chemistry