Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters
Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C-C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables the asymmetric functionalization of MCPs with NH<sub>2</sub>-unprotected amino acid esters. This reaction proceeds through a regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino acid esters bearing nonconjugated terminal alkene units. Mechanism studies indicate that the ring-opening pathways are irreversible and the ultimate regioselectivity is governed by palladium catalysis. The products can be utilized in the construction of chiral dihydropyrazoles, α-methyl aspartic acid derivatives, and analogues of VPC01091 and BMS-986104.
Authors
- Zhu‐Lian Wu (ORCID: https://orcid.org/0000-0001-8444-4028)
- Fang Zhu (ORCID: https://orcid.org/0000-0001-5665-7042)
- Wen Wei (ORCID: https://orcid.org/0000-0001-5100-8545)
- Shao‐Fei Ni (ORCID: https://orcid.org/0000-0001-9860-2138)
- Tian Cai (ORCID: https://orcid.org/0000-0002-9668-6750)
- Hui He (ORCID: https://orcid.org/0000-0002-1685-6618)
- Qi‐Xiang Guo (ORCID: https://orcid.org/0000-0002-0405-7958)
- H.‐P. GUAN
Institutions
- Southwest University (CN)
- Shantou University (CN)
- Ji Hua Laboratory (CN)
- Chongqing Municipal Government (CN)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-01-10
- DOI
- https://doi.org/10.1021/jacs.4c16934
- Citations
- 12
- Primary Topic
- Cyclopropane Reaction Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 11.23
Funders
- Shantou University
- National Natural Science Foundation of China
- Southwest University
- Basic and Applied Basic Research Foundation of Guangdong Province