Pd‐Catalyzed [2+2+1] Coupling of Alkynes and Arenes: Phenol Diazonium Salts as Mechanistic Trapdoors

Abstract

Alkynes and phenol diazonium salts undergo a Pd-catalyzed [2+2+1] cyclization reaction to spiro[4,5]decatetraene-7-ones. This structure was confirmed for one example by X-ray single-crystal structure analysis. The reaction is believed to proceed through oxidative addition of the phenol diazonium cation to Pd(0), subsequent insertion of two alkynes, followed by irreversible spirocyclization.

Palladium(0)‐Catalyzed Intermolecular Carbocyclization of (1,n)‐Diynes and Bromophenols: An Efficient Route to Tricyclic Scaffolds

“…[16,17] Next, we sought to investigate the scope with respect to the bromophenols for the [2+ +2+ +1] cyclization (Table 3). More specifically, the use of ad ialkyl-diaryl mixed diyne (2r)l ed to 3r,w ith aq uaternary carbon center.T his reaction is challenging for prior methods using two different types of individual alkynes.…”

“…[12][13][14][15][16][17] Thel ack of control is even more severe in [2+ +2+ +1] cyclizations, [16,17] generally leading to three inseparable regioisomers in apoor ratio.T oaddress this problem, we postulated that the utilization of carbon-or heteroatom-tethered (1,n)-diynes,w hich possess an interintramolecular feature,toreact with either phenol diazonium salts or b-naphthols would provide an effective solution by the regiospecific construction of am ore interesting tricyclic framework. [16,17] Intrigued by the recent advances on palladium(0)-catalyzed domino reactions of aryl halides with (1,n)-diynes for generating diversified polycycles, [18] we used the most abundant, commercially available bromophenols for promoting ap alladium(0)-catalyzed dearomative cyclization reaction with the tethered diynes.O ur task was to find suitable reaction conditions to enable the desired [2 + 2 + x] (x = 1o r2 )cyclization process,t hrough the dearomatization of phenols,b yp reventing the unwanted [2+ +2+ +2] aromatization of two reactants [19] and the self-consumption of bromophenols either through diarylether formation [20] or dehalogenation. [16,17] Intrigued by the recent advances on palladium(0)-catalyzed domino reactions of aryl halides with (1,n)-diynes for generating diversified polycycles, [18] we used the most abundant, commercially available bromophenols for promoting ap alladium(0)-catalyzed dearomative cyclization reaction with the tethered diynes.O ur task was to find suitable reaction conditions to enable the desired [2 + 2 + x] (x = 1o r2 )cyclization process,t hrough the dearomatization of phenols,b yp reventing the unwanted [2+ +2+ +2] aromatization of two reactants [19] and the self-consumption of bromophenols either through diarylether formation [20] or dehalogenation.…”

“…However, the envisioned transformations with tethered diynes did not proceed at all under the precedented reaction conditions. [16] Herein, we present our efforts on this subject. [16] Herein, we present our efforts on this subject.…”

“…Theenvisioned reaction was first realized by heating amixture of 1a and 2a in THF at 110 8 8Cinthe presence of 5.0 mol %of Pd(OAc) 2 ,6.0 mol %PPh 3 ,and 2.0 equivalents of K 2 CO 3 .The desired tricyclic product 3a was obtained in 53 %y ield (entry 1), without generating any other undesirable side products. Finally,asolvent screening was carried out (entries [14][15][16][17][18], and the reaction was dramatically improved by switching to 1,4-dioxane as the solvent, thus providing 3a in 86 %y ield upon isolation (entry 18). By using the inexpensive ligand PPh 3 ,s everal other palladium precursors were then evaluated (entries 7-9), thus showing inferior performance in comparison with that of Pd(OAc) 2 .N ext, K 3 PO 4 ,KOAc, and Na 2 CO 3 were found to be effective for the reaction (entries 10-12), whereas Cs 2 CO 3 completely shut down the reaction (entry 13).…”

“…In this context, our groups, [12] as well as that of MascareÇas and Gulías, [13] Lam, [14] and You [15] have independently de- scribed the two-component intermolecular annulations between phenol-based biaryls and internal alkynes by as equence of aryl-metal species formation, by either aC À H cleavage [12a,c, 13-15] or oxidative addition to the C À Br bond, [12b,d] carbometalation of one alkyne unit, and eventually terminated by dearomatization of the phenolic ring to provide spirocycles.I n2 011, Schmidt and co-workers reported an impressive example of palladium-catalyzed [2+ +2+ +1] spiroannulation of phenol diazonium salts with two equivalents of diarylalkynes by formation of three C À Cbonds . [16] Soon after, we developed as imilar cyclization reaction of b-naphthols with two equivalents of alkynes through consecutive carbopalladation to the CÀCt riple bonds under oxidative conditions. [17] These intermolecular reactions proceeded smoothly by coupling easily accessible phenol derivatives with symmetric alkynes,but asignificant challenge with these processes is the ability to control the regioselective insertion of an unsymmetrical alkyne.…”