Construction of spirocarbocycles via gold-catalyzed intramolecular dearomatization of naphthols

Abstract

A highly efficient, gold-catalyzed intramolecular dearomatization reaction of naphthols via 5-endo-dig cyclization is described. This facile and direct approach furnishes spirocarbocycles in excellent yields under mild conditions.

A Gold‐Catalyzed Domino Cyclization Enabling Rapid Construction of Diverse Polyheterocyclic Frameworks

“…Thus, it was ascertained that both steps,t he dearomatization/ipsocyclization to form 2s' ' and the subsequent Michael addition to produce polycycle 2s,a re catalyzed by cationic gold species. [21] On the basis of these observations and previous reports, [20][21][22] apostulated reaction mechanism for this overall transformation is illustrated in Scheme 3. First, ac ationic gold(I) species generated in situ activates the triple bond of the Ugi adduct (AE)-1.T hen nucleophilic attack of the phenol on the activated triple bond occurs in a5 -endo-dig fashion [a] All reactions were performed with 1 (0.20 mmol) and IPrAuOTf (10 mol%) in ascrew-cap vial with CHCl 3 (2 mL) for 3-24 h; all yields are for the isolated product.…”

“…Pleasingly,t he reactions proceeded well under modified conditions in the case of hydroxy-and alkoxy-substituted benzaldehydes,d elivering the benzene-annulated tricyclic heterocycles 6a-e [17] in moderate to good yields.T he application of as ubstrate with ap yrrolidine-substituted benzene ring gave the benzene-annulated tricycle 6g in 71 %y ield at room temperature.U nfortunately,t he use of piperidine-or morpholine-substituted benzaldehydes delivered solely the spirocarbocyclic products 6h' ' and 6i' ' at room temperature, and even when the reaction was carried out at 115 8 8Cfor 48 h the desired benzene-annulated tricycles 6h and 6i were obtained only in low yields.M oreover,o nly the spirocarbocyclic products were observed in the case of substrates 5 derived from simple 2-naphthaldehyde and benzaldehyde when the reactions were carried out at 115 8 8Cf or 48 h. [19] Theobtained spirocarbocyclic intermediates indicate that the gold-catalyzed dearomatization/ipso-cyclization proceeds first in a5 -endo fashion. [20] To shed light on the subsequent Michael addition, we examined reactions of the spirocarbocyclic intermediate 2s' ' under different conditions (Scheme 2). Thetreatment of intermediate 2s' ' with IPrAuOTf (10 mol %) at 115 8 8Cf or 24 hd elivered the desired polycyclici ndole derivative 2s in 95 %y ield.…”

Gold(I)‐Catalyzed Allene–Diene–Alkyne Coupling Reaction to Polycycles

“…[ 13 ] However, gold has been rarely used in CADA reactions compared to other transition metals. [ 14–17 ] An example of gold‐catalyzed dearomatization involving one alkyne unit was shown by Bandini et al [ 18 ] They converted naphthyl propargyl ethers 1 to naphthalene‐2‐one derivatives 2 (Scheme 1a). This reaction can be considered as a Claisen rearrangement with subsequent intramolecular hydroxy group addition to the newly formed allene.…”

Design, Synthesis and Anticancer Evaluation of Spiro [cyclohexane‐1,1′‐indene]‐2,5‐diene Analogues

“…However, due to the distinctive properties of Spirodienones, especially the relatively congested quaternary carbon centre, it has been a challenging task for chemists to develop a synthetically applicable methodology. Hence, highly efficient, mild, and streamlined synthetic routes are still in great demand to construct these substrates …”