Trifluoroethanol-assisted asymmetric propargylic hydrazination to α-tertiary ethynylhydrazines enabled by sterically confined pyridinebisoxazolines
Yi Gong, Zheng Zhang, H. Liu, Tao Wang, Mengmeng Jiang, Nan Feng, Pei‐Ying Peng, Huimin Wang, Feng Zhou, Xin Wang, Jian Zhou
Abstract
We report the highly enantioselective Cu-catalyzed asymmetric propargylic substitution (APS) of α-tertiary propargylic electrophiles using hydrazines and hydroxylamines as a fruitful strategy to access multifunctional α-tertiary hydrazines or hydroxylamines. Using trifluoroethanol (TFE) as the solvent play a key role to decrease the nucleophilicity of hydrazines to suppress side reactions such as elimination, thus improve the yield and the enantioselectivity. NMR analysis and theoretical calculations suggest the formation of an H-bond adduct of TFE with hydrazide, stabilized by multiple H-bonding interactions, including C–F···H–N interaction. The sterically confined pyridinebisoxzolines (PYBOX), featuring a bulky benzylthio shielding group also contribute to the excellent enantioselectivity. Aryl- and aliphatic-ketone-derived α-ethynylalcohol carbonates, α-tertiary α-ethynyl epoxides, cyclic carbonates and and α-hydroxycarboxylates all are competent substrates to afford α-tertiary α-ethynylhydrazines with high structural diversity. The obtained products can be readily converted into various α-tertiary hydrazines and azacycles featuring an aza-quaternary stereocenter. Copper-catalyzed asymmetric propargylic substitution of α-tertiary propargylic electrophiles using hydrazines and hydroxylamines can access multifunctional α-tertiary hydrazines or hydroxylamines. Here the authors use a sterically confined pyridinebisoxazolines to improve yields and enantioselectivity, supported by NMR analysis and theoretical calculations.