Exception to the ortho Effect in Palladium/Norbornene Catalysis

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

“…Soon afterwards,anon-oxidative version was enabled by Pd 0 catalysis. [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).This work stems from palladium/norbornene (NBE) chemistry,w hich was originally discovered by Catellani et al [17] Seminal works [18] by Catellani and Lautens revealed that am yriad of biaryl-containing carbocyclic and heterocyclic compounds (III)could be obtained through palladiumcatalyzed ortho-arylation of an aryl iodide (I)w ith ab ifunctional aromatic reagent (II)f ollowed by intramolecular ring closure with NBE as atransient mediator (Scheme 2). [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. However,a dditional challenges arise from the fact that:1)the utilization of aromatic motif II,which is prone to undergo dearomatization, dramatically increases the risk for the direct cyclization of intermediate B to provide NBE-containing spirocarbocylce VI (path b), [16,19] and 2) the two-component annulation of two [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).…”

“…These processes are initiated by NBE-assisted CÀHp alladation to form five-membered palladacycle A,w hich then reacts with haloarene II to generate biarylpalladium species B.S ubsequent elimination of NBE through b-carbon elimination then occurs to give the key intermediate C.Inconnection with our persistent interest in the development of cooperative CÀH activation/dearomatization reactions, [9, 14d] we wondered whether the in situ formed intermediate C could be intercepted with alkyne IV through ad earomative pathway to produce spirocyclicc ompound V (path a). However,a dditional challenges arise from the fact that:1)the utilization of aromatic motif II,which is prone to undergo dearomatization, dramatically increases the risk for the direct cyclization of intermediate B to provide NBE-containing spirocarbocylce VI (path b), [16,19] and 2) the two-component annulation of two equivalents of I with alkyne V might form phenathrene product VII (path c). [20] Therefore,the key for the envisioned reaction is to find suitable conditions to effectively prevent the unwanted side reactions.…”

Palladium-Catalyzed Double C–H Functionalization of Arenes at the Positions <i>ortho</i> and <i>meta</i> to Their Directing Group: Concise Synthesis of Benzocyclobutenes

“…[5][6][7] Benzyne is a highly reactive species because of its strained structure, making it a useful intermediate for the transformation of aromatic rings through cycloaddition and multicomponent reactions. [1][2][3][4] Regarding the ortho C-H functionalization of arenes, various norbornene-mediated strategies have been developed for the ipso and ortho functionalization of aryl halides using palladium catalysts, including those reported by Catellani et al, 8,9) Lautens and colleagues, [10][11][12] Malacria and colleagues, 13) Dong Z. and Dong G., 14) Liang and colleagues, 15) Ritter and colleagues 16) and Zhou and colleagues. 17) Although these strategies can be applied to various transformations involving aromatic rings by simply changing the reagents, they need at least one reactive substituent such as a halogen at the appropriate position of the aromatic ring to achieve the desired transformation.…”

“…The nature of the protecting group on the nitrogen atom of the amino acid was also found to be very important. Although the use of a formyl or acetyl (Ac) group did not lead to an improvement in the conversion of 1a (Table 2, entries 10, 11), the use of a carbamate protecting group such as a t-butyloxycarbonyl (Boc), methoxycarbonyl or (−)-menthyloxycarbonyl (Men) group led to an increase in the conversion (Table 2, entries [12][13][14]. In contrast to previous reports from the literature, 34) the use of a smaller charge of (−)-Men-Val-OH (5 mol%) led to an increase in the conversion of 1a (Table 2, entry 15).…”