Chiral phosphoric acid catalyzed aminative dearomatization of α-naphthols/Michael addition sequence

Abstract

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.

Dearomatizing Amination Reactions

“…[62] In an elegant extension of the approach, You and coworkers developed a tandem process involving enantioselective and para-selective amination of α-naphthols or phenols (Scheme 29A). [63] Here, the initially generated enone is trapped by a pendant N-, O-or C-based nucleophile to provide polycyclic systems 89 a-d with very high levels of efficiency. Conceptually, this sequence is related to Antilla and Zhang's methodology involving indole systems 90 (Scheme 29B).…”

Transition-Metal-Free [3+2] Dehydration Cycloaddition of Donor-Acceptor Cyclopropanes With 2-Naphthols

“…desirable. We notice that 2-naphthols commonly serve as important aromatic feedstocks in organic chemistry (Zhuo and You, 2013;Wang et al, 2015;Yang et al, 2015;Zheng et al, 2015;Cheng et al, 2016;Shen et al, 2017;Tu et al, 2017;Fang et al, 2018;Liu et al, 2018;Xia et al, 2019;Zhang et al, 2020), and Biju disclosed a formal (3 + 2) cyclopentannulation of 2-naphthols and D-A cyclopropanes catalyzed by Bi(OTf) 3 and KPF 6 (Kaicharla et al, 2016). But in the case of a reaction involving D-A cyclopropanes with vinyl as the only substrate, the cyclization product is obtained in an unsatisfactory yield (42%), which greatly inhibits the universality of the reaction.…”

Progress of Dialkyl Azodicarboxylates in Organic Transformations

“…Dialkyl azodicarboxylates have also been used for the construction of C−N, C=O and C−S/Se bonds. Zheng and You's research group demonstrated an intermolecular asymmetric dearomatization reaction of α‐naphthols using chiral phosphoric acid and dialkyl azodicarboxylates [43] . Various α‐naphthols bearing a tethered nucleophile at the C4 position were treated with 10 mol % of chiral phosphoric acid and 1.5 equiv.…”