TY - JOUR T1 - Chiral phosphoric acid catalyzed aminative dearomatization of α-naphthols/Michael addition sequence. AU - Xia,Zi-Lei, AU - Zheng,Chao, AU - Xu,Ren-Qi, AU - You,Shu-Li, Y1 - 2019/07/17/ PY - 2019/03/25/received PY - 2019/06/11/accepted PY - 2019/7/19/entrez PY - 2019/7/19/pubmed PY - 2019/7/19/medline SP - 3150 EP - 3150 JF - Nature communications JO - Nat Commun VL - 10 IS - 1 N2 - Asymmetric dearomatization reactions have recently emerged as a powerful tool for the rapid build-up of the molecular complexity. Chiral three-dimensional polycyclic molecules bearing contiguous stereogenic centers can be synthesized from readily available planar aromatic feedstocks. Here we report that an intermolecular asymmetric dearomatization reaction of α-naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring is achieved by a chiral phosphoric acid. The reaction proceeds via a highly chemo- and regioselective aminative dearomatization/Michael addition sequence, affording a wide array of functionalized cyclic ketones in good yields (up to 93%) with excellent enantioselectivity (up to >99% ee). The catalyst loading can be reduced to 0.1 mol%. Preliminary mechanistic investigations identify that the enantioselectivity is established in the dearomatization step, while the Michael addition is the rate-limiting step. A working model accounting for the origin of the stereochemistry is proposed based on DFT calculations. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/31316064/Chiral_phosphoric_acid_catalyzed_aminative_dearomatization_of_α_naphthols/Michael_addition_sequence_ DB - PRIME DP - Unbound Medicine ER -