Intermolecular Enantioselective Dearomatization Reaction of β‐Naphthol Using meso‐Aziridine: A Bifunctional In Situ Generated Magnesium Catalyst

Abstract

A direct, facile, and highly diastereo‐ and enantioselective dearomatization reaction of β‐naphthol derivatives with aziridines has been developed for the first time. A newly designed Box–OH ligand was employed for an in situ generated magnesium catalyst and proved to be efficient. The corresponding dearomatization product was transformed into a polycyclic scaffold and polyhydroxylated compound. 1H NMR studies revealed the activation mode of the dearomatization process of β‐naphthols, and a clear positive nonlinear effect was observed in the reaction, and provides insight into the coordination environment around the MgII center and the possible active species.

Application of a CC Bond‐Forming Conjugate Addition Reaction in Asymmetric Dearomatization of β‐Naphthols

“…Finally,aplausible mechanism for this dearomatization was proposed on the basis of our previous work [7] and studies of the phenol/Mg crystallographic structures. [17] As illustrated in Figure 2, after reaction between L9 and Bu 2 Mg, either the precatalyst Ao ri ts dimer B is formed.…”

“…[7,8] However,s urprisingly,t o date,t here are almost no reports on catalytic asymmetric dearomatization of phenols by using of common conjugate addition reactions.V ery recently,t he breakthrough work utilizing CÀNb ond-forming conjugate additions in direct asymmetric dearomatization of b-naphthols was realized by the groups of Youa nd Luan independently,a lthough they employed different catalytic systems (Figure 1a). [9,10] Nevertheless,t he application of other conjugate addition reactions in direct enantioselective dearomatization of b-naphthols is still unrealized, yet highly desirable.H erein, we report an enantioselective dearomatization reaction of b-naphthols by aC À Cb ond-forming conjugate addition employing propargylic ketones as reactive partners (Figure 1b).…”

“…We therefore evaluated the effects of other oxazoline-OH ligands derived from orthohydroxyphenylacetic acid, which was developed by us recently. [7] Thes creening process showed that moderate ee values could be obtained while introducing this type of chiral ligand into the dearomatization reaction. Fortunately, we identified L9 as ap romising chiral ligand, which led to higher enantioselectivity and Z/E selectivity.Next we turned to improving the results by evaluating all the reaction parameters.B yr unning the reaction at lower temperatures, we were pleased to observe that the ee value increased to 88 %a long with enhancement of the Z/E selectivity to 8.5:1 …”

Iridium‐Catalyzed Asymmetric Allylic Dearomatization by a Desymmetrization Strategy

“…Despite the fact that there are known examples of stepwise dearomatization of para-substituted phenols/desymmetrization of cyclohexadienones, [3] known one-step desymmetrizing dearomatization reactions are generally limited to racemic or chiral auxiliary-assisted diastereoselective processes. [5] Therefore,todevelop highly efficient CADA reactions by applying adesymmetrization strategy is of great importance. [5] Therefore,todevelop highly efficient CADA reactions by applying adesymmetrization strategy is of great importance.…”

“…[4] To the best of our knowledge,t he only example of ac atalytic asymmetric process was reported by Wang and coworkers,in which the asymmetric dearomatization of b-naphthols was coupled with desymmetrization of meso-aziridines. [5] Therefore,todevelop highly efficient CADA reactions by applying adesymmetrization strategy is of great importance.…”