Nanotechnologies / Materials
Organic semiconductors, Electroluminescence materials, Medicinal chemistry

Catalytic vinylene transfer reaction for the direct
construction of multi-ring systems
Department of Applied Chemistry, Graduate School of Engineering
Associate Professor (Lecturer) Yuji Nishii
Researchmap https://researchmap.jp/y_nishii

Nanotechnologies / Materials

Abstract
Transition-metal-catalyzed C–H activation and subsequent oxidative cyclization with alkynes has been a powerful tool for the synthesis of polycyclic aromatic compounds. Despite the substantial
progress in this field, it is still a significant challenge to establishsynthetic methodologies for the construction of non-substituted
vinylene-fused aromatics. We have developed a catalytic “vinylenetransfer strategy” adopting vinylene carbonate as an acetylene
surrogate. Vinylene carbonate also acts as an internal oxidant toregenerate the catalytically active species in situ; thus, no externaloxidant is required to trigger the oxidative annulation. This protocol
is applicable to the direct synthesis of various polycyclic heteroaromatics.

of such polycyclic molecules in various biologically active compounds (pharmaceuticals, agrochemicals, etc.) and manufacturedfunctional molecules (luminescence materials, semiconductor, solar cells, etc.), these new reaction systems would highly reinforce
the synthetic utility of the direct annulation strategy.

▍ Background & Results
Polycyclic heteroaromatic scaffolds are ubiquitous in many
natural compounds and have been a key motif in a wide range ofmanufactured functional molecules. Accordingly, tremendous research interest has been focused on the development of new andefficient synthetic methods for constructing fused-ring skeletons.
Transition-metal-catalyzed C−H activation and subsequent oxidative annulation with alkynes or their equivalents have emerged
as promising synthetic tools for the assembly of heterocycles. Thismethod allows us to construct various fused-ring systems withsimple manipulations; however, most of these reactions are only
applicable to internal alkynes. This limitation signiﬁcantly takes
from the practical value of the annulative coupling reaction because a non-substituted vinylene fragment cannot be installed via
the catalysis. Moreover, a stoichiometric amount of external oxidant
is usually required to ensure the catalytic turnover, leading to theformation of undesired byproducts.
To address this issue, we envisioned using vinylene carbonate
as an oxidizing acetylene surrogate. Vinylene carbonate is abench-stable reagent with bulk production as an electrolyte andfor polymer chemistry. Upon liberation of the [CO3]2− anion (formal two-electron reduction), vinylene carbonate might act as a
two-electron internal oxidant under proper reaction conditions toestablish a redox-neutral reaction system. Overall, only H2CO3 (orH2O + CO2) would form as a byproduct. With this picture in mind,
we investigated the annulative coupling using vinylene carbonate
as a coupling partner and, to our delight, various vinylene-fused
heteroaromatic compounds were successfully synthesized throughthe C−H/N−H, C−H/C−H, and C−H/O−H oxidative cyclization.
.

▍ Significance of the research and Future perspective

Notable features of this reaction system are that (1) non-substituted vinylene-fused cyclic compounds can be obtained directly,
without any pre-functionalization, and (2) no external oxidant norbase is required for the catalytic turnover because the vinylene
carbonate fulfills both the functions. Considering a wide prevalence

P a t e n t
Ghosh, Koushik; Nishii, Yuji; Miura, Masahiro; Rhodium-Catalyzed Annulative Coupling Using Vinylene Carbonate as an Oxidizing Acetylene Surrogate.
ACS Catalysis. 2019; 9: 11455-11460. doi: 10.1021/acscatal.9b04254.
Ghosh, Koushik; Nishii, Yuji; Miura, Masahiro; Oxidative C-H/C-H Annulation of Imidazopyridines and Indazoles through Rhodium-Catalyzed Vinylene
Tr e a t i s eTransfer. Organic Letters, 2020; 22: 3547-3550, doi: 10.1021/acs.orglett.0c00975.
Mihara, Gen; Nishii, Yuji; Miura, Masahiro et al. Concise Synthesis of Isocoumarins through Rh-Catalyzed Direct Vinylene Annulation: Scope and Mechanistic Insight. Organic Letters. 2020; 22: 5706-5710. doi: 10.1021/acs.orglett.0c02112.
UR
L http://www.chem.eng.osaka-u.ac.jp/~miura-lab/
K e y w o r d catalysis, organic electronics, coupling reaction