Construction of the Benzomesembrine Skeleton: Palladium(0)‐Catalyzed Intermolecular Arylative Dearomatization of α‐Naphthols and Subsequent Aza‐Michael Reaction

Abstract

A novel palladium(0)-catalyzed intermolecular arylative dearomatization of α-naphthols and subsequent aza-Michael reaction is described. Two adjacent stereocenters were constructed efficiently through consecutive arylative dearomatization and Michael addition reactions. By utilizing this method, structurally diverse benzomesembrine derivatives were synthesized with excellent yields and chemoselectivity. The benzomesembrine products were shown to undergo versatile functional-group transformations.

Recent Advances in the Catalytic Dearomatization of Naphthols

“…Moreover, the same team designed a new class of 1‐(2‐bromophenethyl)‐2‐naphthols 11 that could provide dearomatized spiro‐adducts 12 in yield up to 95 % with in situ formed [(Pd(C 3 H 5 )Cl) 2 ]/Q‐Phos complex (0.5/1.5 mol‐%, Scheme b). [10b] In all cases, an excellent C(1)‐ vs. O‐arylation ( 12 : 12' up to > 20:1) was detected.…”

“…In 2017, the arylating/Michael addition dearomatization sequence of 1‐naphthols was documented by You. [10a] Here, the use of the [(Pd(prenyl)Cl) 2 ]/Q‐Phos (5/11 mol‐%) complex enabled the site‐selective arylation at the C(4) position, with subsequent trapping of the resulting enone unit by the tethered C‐ or N‐based nucleophilic side‐arm. A range of benzomesembrine skeletons 10 were isolated in moderate to excellent yield (30–94 %, Scheme a).…”

“…Interestingly, the Luan group succeeded in realizing a one‐pot C(1)‐arylation of naphthols and subsequent dearomatization reaction via [Pd(II)]/DavePhos‐catalyzed insertion of internal alkynes. [10c] Overall, the three‐component process involves a [2+2+1] spiro‐annulation that resulted in the spiro[indene‐1,1'‐naphthalen]‐2'‐ones 6 (yield: 46–87 %). Mechanistically, consecutive Catellani type C–H activation and unsymmetrical biaryl coupling delivered intermediate D , which could lead to intermediate E via an alkyne migratory insertion process.…”

Manipulation of Spiroindolenine Intermediates for Enantioselective Synthesis of 3‐(Indol‐3‐yl)‐Pyrrolidines

“…[13] Theunprotected pyrrolidine derivative 12 was afforded in 71 %yield. Theketone group of 4a can be reduced to methylene moiety by Wolff-Kishner-Huang reduction, [14] leading to 13 in 63 %y ield. In addition, the tertiary alcohol 14 was prepared in 88 %y ield by the treatment with Grignard reagent (PhMgBr).…”

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

“…In 2017, we reported a Pd-catalyzed arylative dearomatization/ aza -Michael addition sequence between aryl bromide and α -naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring 59 . The exclusive chemo-, and regioselectivity favoring the C4 position among the multiple potential nucleophilic sites encouraged us to further probe the possibility of developing a highly enantioselective dearomatization of α -naphthols/Michael addition sequence.…”