A C3-Symmetric Amino Organocatalyst for Asymmetric Synthesis of Warfarin and Analogues: Mechanistic Insight from ESI-MS Spectrometry and Computational Calculations

A novel C3-symmetric multi-amino catalyst was synthesized and evaluated in the asymmetric Michael addition to produce warfarin and its analogues. The multi-amino catalyst turned out to be efficient up to 1 % molar without the use of acidic additives providing the desired product in 82 % yield and maintaining good level of enantioselectivity. ESI-MS experiments together with data supplied by theoretical models allowed us the understand the operating mechanism of the catalyst, clarifying the role of the amine functions and confirming the catalyst's multifunctionality. The presence of three active catalytic sites makes it easy its anchoring to silica as solid support for applications in heterogeneous phase catalysis. A C3-symmetric amino-based organocatalyst can be easily prepared starting from chiral trans-N-Boc-1,2-diaminocyclohexane. Its activity on asymmetric synthesis of warfarin and analogues has been explored allowing moderate-high yields and good stereoselectivity with very low catalyst loading. Up to three active units work in the catalytic process as confirmed by offline ESI-MS experiments. In addition, DFT calculations supported the plausible reaction mechanism. image