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