Manufacturing technologies
Drug discovery, Molecular catalysts, Functional Molecules

Palladium-catalyzed skeletal rearrangementof cyclobutanones
Department of Applied Chemistry, Graduate School of Engineering
Assistant Professor Yusuke Ano
https://researchmap.jp/yusukeano?lang=en

Abstract
Organic compounds, such as pharmaceuticals, plastics, andpigments, support our lives. Synthesis of desired organic compounds is typically performed by sequentially transforming a partof readily available starting materials. In contrast, if the carbon-carbon bonds constructing the framework of organic compounds canbe transformed into other functional groups, completely different
molecular frameworks can be synthesized in one step. In thisstudy, we developed the palladium-catalyzed skeletal rearrangement of cyclobutanones, leading to the formation of 1-indanones.

General Strategy in Organic Synthesis

many steps are required due to the sequential transformation

Strategy through the Carbon−Carbon Bond Cleavagecarbon−carbon bonds:
framework of organic compounds

Manufacturing technologies▍ Background & Results
Catalytic transformation of carbon-carbon bonds has the potential to provide a chemical technology to realize a society based oncarbon cycling. Transition metal-catalyzed carbon-carbon bondcleavage has been studied for a long time. However, the development of new catalysts is still required because the scope ofcarbon-carbon bonds for this approach is limited. We developed
the palladium-catalyzed skeletal reorganization of cyclobutanones
into 1-indanones via the dual cleavage of carbon-carbon and carbon-hydrogen bonds. Although catalytic transformation of cyclobutanones into 1-indanones has been reported, the introduction ofreactive functional groups or directing groups is needed to performthe reaction successfully. In contrast, our method can perform thedirect transformation of simple cyclobutanones into 1-indanones.
Screening of reaction conditions revealed that the use of aN-heterocyclic carbene (NHC) ligand is effective, leading to thedesired skeletal rearrangement of 3-arylcyclobutanone. A variety offunctional groups such as nitro, ether, cyano, and fluorine groups
are compatible under the reaction conditions. The reaction of a
spiro-type cyclobutanone afforded a polycyclic ketone in goodyield. When the reaction was conducted in the presence of nucleophiles such as alcohols, amines, and arylboronates, giving thecorresponding ring-opening products.

▍ Significance of the research and Future perspective

cleavage/functionalization of themolecular framework enables theshort-step synthesis

Figure 1

Overview

Figure1

Palladium-catalyzed skeletal rearrangement via the cleavage ofcarbon−carbon and carbon−hydrogen bonds is developed.

cyclobutanone

1-indanone
previous works: introduction of an extra
functional group as a foothold was required
this work: direct transformation of simple
cyclobutanones into 1-indanones

Figure 2

Figure2

Scope of the Reaction

This report demonstrated the new reactivity of a Pd(0)/NHC
complex that can serve to activate inert carbon-carbon and carbon-hydrogen bonds without the assistance of “foothold” functionalgroups. This would contribute to the development of new methods
for the step-economical organic synthesis. Further research regarding the skeletal rearrangement and editing of organic compounds
will also be promoted by this research, serving pharmaceutical andagrochemical research and development.
the Pd/NHC catalyst isapplicable to the reaction with
nucleophiles
Figure 3

Figure3

P a t e n t
Tr e a t i s eAno, Yusuke; Takahashi, Daichi; Chatani, Naoto et al. Palladium-catalyzed skeletal rearrangement of cyclobutanones via C-H and C-C bond cleavage.
ACS Catalysis 2023, 13(4), 2234–2239. doi: 10.1021/acscatal.2c06389

URL
K e y w o r d palladiium catalyst, cyclobutanones, skeletal rearrangement