Atroposelective Synthesis of Isoxazole-Derived Amino Alcohols via Organocatalytic Arylation Reaction
Liang Liu , Hui Wang , Ting Han , Wenkun Luo , Chao Liu , Jun Zhou , Weiwei Luo
Chinese Journal of Chemistry ›› 2025, Vol. 43 ›› Issue (20) : 2661 -2668.
Atroposelective Synthesis of Isoxazole-Derived Amino Alcohols via Organocatalytic Arylation Reaction
The chiral phosphoric acid catalyst enables the atroposelective arylation of 5-aminoisoxazoles and quinones by accelerating the kinetics of the enantioselective catalytic reaction, effectively outcompeting and even suppressing the uncatalyzed racemic background reaction. In this strategy, a large panel of axially chiral isoxazole-derived amino alcohols was synthesized with generally high yields and excellent enantioselectivities. The method features mild reaction conditions, broad functional group compatibility and good scalability. X-ray crystallography and thermal racemization experiments revealed the important role of six-membered intramolecular O−H···O hydrogen bonding in stabilizing the configurations, which exhibit markedly different racemization barriers in protic and aprotic solvents. Moreover, preliminary mechanistic studies, including nonlinear effects and control experiments were conducted to elucidate the reaction mechanism and activation mode. This approach not only provides an efficient method for constructing pentatomic isoxazole scaffolds, but also expands the family of axially chiral amino alcohols.
Axial chirality / Asymmetric catalysis / Amino alcohols / Arylation / Hydrogen bonding / Isoxazoles / Organocatalysis / Quinones / Solvent effects
2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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