Background and Originality Content
Cyclobutanones have served as unique building blocks in organic synthesis because it is strained and possesses high ring strain energy.[1] Low valent transition metals can easily insert into their C(carbonyl)−C bonds to form 5-membered metallacyclopentanones, which are capable of performing various synthetic transformations to access diverse complex skeletons.[2] A well-known reactivity of the metallacyclopentanones involves the migratory insertion of π-systems such as alkynes, akenes and carbonyl functionality (Scheme 1a).
Scheme 1 Strategies for transition-metal-catalyzed C‒C σ-bond activation of cyclobutanones
Despite many efforts have been made in discovery of new reactvities of cyclobutanones, there are some limitations: (1) the main catalysts enabling the oxidative cleavage of C(carbonyl)−C bonds of cyclobutanones in literature are Rh catalysts or Ni catalysts,[3,4] which hampered the exploitation of new synthetic reactions; and (2) the reaction of C–H bond with cyclobutanones under the transition metal-catalytic condition is still underdeveloped. As shown in Scheme 1b, Matsuda and co-workers presented the only example on the reaction of C–H bond with cyclobutanones involving oxidative addition of C(carbonyl)−C bond and sequential intramolecular C–H bond cleavage by use of expensive Rh-catalyst in 2015.[5] To ensure the reaction, as high as 150 °C is needed and a sub- or stoichiometric pyridine was added to serve as a directing group in situ. Their deuterium experiments proved that C–H bond cleavage step under the reaction involved intramolecular σ-complex-assisted metathesis. Encouraged by our group and Murakami’s recent work on palladium-catalyzed ring expansion reactions of benzocyclobutenones that involves the oxidative addition of the C–C bond directly[6] and the versatility of Pd catalyst in C–H bond activation,[7] we wonder if C(carbonyl)−C bonds of cyclobutanones can be selectively cleaved by palladium(0) catalyst in the absence of directing group to form the five-membered palladacyclopentanones, which would trigger the successive intramolecular C–H bond activation, delivering ring expansion product. With this idea in our mind, herein, we realized the first palladium-catalyzed skeletal reorganisation of phenyl cyclobutanones involving successive cleavage of C(carbonyl)−C bonds and C−H bond cleavage, which constitutes a rapid access to diverse indanones.[8,9] Our further study indicates that the Pd-catalytic system in this reaction involves different C–H bond mechanism from Matsuda’s Rh-catalytic system with different scope of substrates.
Results and Discussion
Results
We commenced the optimization of reaction conditions using diphenylcyclobutane 1a as standard substrate (Table 1). Based on the previous works, we first evaluated transition metal catalysts that are capable of activating C‒C bond of cyclobutanones in the previous works. Rh(PPh3)3Cl and Ni(cod)2 with the ligand PCy3 or IPr were inactive in the absence of directing group (entries 1–3). We also use Pd(OAc)2 as a catalyst to screen different ligands. Phosphine ligands didn’t show any reactivity (entries 4–6). Encouragingly, when the NHC ligand IPr, generated in situ by the deprotonation of IPr·HCl with KOt Bu, was used, the reaction afforded the desired product 2a in 73% yield (entry 7). Using IMes as the ligand diminished the yield to 45% (entry 8). When Pd(OAc)2 was replaced with [Pd(allyl)Cl]2 or Pd(Pt Bu3)2, the yields dropped to 70% and 10%, respectively (entries 9 and 10). Pd(PPh3)4 as the catalyst would shut down the reaction (entry 11). Utilization of (IPr)Pd(allyl)Cl as the catalyst delivered product 2a in 73% yield (entry 12). Replacing the base with NaOt Bu or LiOt Bu didn’t promote the reactivity (entries 13 and 14). K3PO4 showed better activity, providing 2a in 76% yield (entry 15). Increasing the loading of K3PO4 to 50 mol% improved the yield to 81% (entry 16). Reducing the amount of (IPr)Pd(allyl)Cl to 5 mol% only led to the slightly decrease of the yield (entry 17).
Table 1 Optimization of the Reaction Conditionsa