Palladium-catalyzed dearomative cyclization by a norbornene-mediated sequence: a route to spiroindolenine derivatives

Abstract

The first palladium-catalyzed dearomative cyclization via a modified Catellani-type C-H functionalization has been realized. The new strategy led to a series of spiroindolenine derivatives bearing an all-carbon quaternary spirocenter from simple aryl halides and substituted indoles.

Alkylating Reagents Employed in Catellani‐Type Reactions

“…Since seminal work by the group of Lautens in 2000, this direction has received tremendous attention, and a number of useful annulation strategies were developed based on different intramolecular terminating reactions (Table ). Representatively, the Heck reaction, the redox‐relay Heck reaction, Buchwald–Hartwig amination, α‐arylation of ketones, C−H arylation of electron‐rich heterocycles, dearomatization, and so forth were utilized as the termination steps.…”

Modular Assembly of Spirocarbocyclic Scaffolds through Pd0‐Catalyzed Intermolecular Dearomatizing [2+2+1] Annulation of Bromonaphthols with Aryl Iodides and Alkynes

“…[4] Pioneering examples of transitionmetal-catalyzed dearomative spirocyclizations were realized by the groups of Hamada, [5] You, [6] Buchwald, [7] and Feringa [8] through an intramolecular design by using tethered phenol, [5, 6b, 7a] naphthol, [5, 6f-g, 7a,8] indole, [5b, 6a,c] or pyrrole [6d-e] derivatives to avoid the unwanted heteroatom alkylation/arylation or Friedel-Crafts-type reaction pathway.H owever, further advancement of this intramolecular strategy for building other diversified spirocylces has been dramatically limited, in part due to the need for high-cost substrates that often require multistep synthesis.I nt his context, substantial efforts have been focused on the development of more atom-and stepeconomical intermolecular processes.V ery recently,we, [9] and the groups of Gulías and MascareÇas, [10] Lam, [11] and You [12] have independently demonstrated Ru II -a nd Rh III -catalyzed dearomatizing [3+ +2] spiroannulations of phenol-derived biaryls with alkynes through aC ÀHb ond activation approach. [15] Despite these elegant achievements on two-component processes,t he discovery of related annulations with three distinct starting materials to assemble complex spirocyclic frameworks still remains af ormidable challenge. [13] Moreover,t he potent strategy of palladium-catalyzed two-component dearomative cyclization [14] allowed the direct use of phenol diazonium salts,h alophenols, halonaphthalenes,n aphthols,a nd N-aryl ureas as onecarbon synthons to react with two equivalents of alkynes, thereby leading to various spirocarbocylces.M eanwhile,t he pursuit of Pd 0 -catalyzed dearomative spirocyclizations of indole derivatives with as econd reactant has also seen significant progress.…”

“…Soon afterwards,anon-oxidative version was enabled by Pd 0 catalysis. [15] Despite these elegant achievements on two-component processes,t he discovery of related annulations with three distinct starting materials to assemble complex spirocyclic frameworks still remains af ormidable challenge. [15] Despite these elegant achievements on two-component processes,t he discovery of related annulations with three distinct starting materials to assemble complex spirocyclic frameworks still remains af ormidable challenge.…”

“…At the outset, areaction mixture of 1a, 2a, and 3a in DMF was heated at 100 8 8Ci nt he presence of 5.0 mol %P d(OAc) 2 ,1 2.0 mol %P Ph 3 ,1 .0 equivalent of NBE, and 2.0 equivalent of K 2 CO 3 ,but neither the dearomatizing products (V and VI)n or dibenzofuran (III) [22] were observed under these typical Catellani-reaction conditions, [23] and only side product 7a [20] was obtained through the annulation of 1a with 3a (entry 1). Further results revealed that various phosphine ligands were effective,a nd the troublesome issue of the formation of unwanted 5a and 7a could be addressed (entries [8][9][10][11][12][13][14][15][16][17]. Despite this encouraging outcome with the use of Cs 2 CO 3 ,t he desired transformation suffered from the concomitant generation of byproducts 5a, 6a, [14a, b] and 7a.O ther common solvents and palladium precursors for Catellani-type reactions were tested, but none of them showed apositive effect (entries 4-7).…”

“…[13] Moreover,t he potent strategy of palladium-catalyzed two-component dearomative cyclization [14] allowed the direct use of phenol diazonium salts,h alophenols, halonaphthalenes,n aphthols,a nd N-aryl ureas as onecarbon synthons to react with two equivalents of alkynes, thereby leading to various spirocarbocylces.M eanwhile,t he pursuit of Pd 0 -catalyzed dearomative spirocyclizations of indole derivatives with as econd reactant has also seen significant progress. [15] Despite these elegant achievements on two-component processes,t he discovery of related annulations with three distinct starting materials to assemble complex spirocyclic frameworks still remains af ormidable challenge. [16] Herein we disclose aP d 0 -catalyzed dearomatizing [2+ +2+ +1] spiroannulation of readily available bromonaphthols with aryl iodides and alkynes for the one-step direct assembly of spiro[indene-1,1'-naphthalen]-2'-ones (Scheme 1).…”