Catalyst-controlled regiodivergence in enantioselective synthesis of spirocyclic γ- versus δ-lactams.

Shao-Hua Wu, Fan Gong, Yang-Bo Bi, Yi-Ze Bai, Cheng Zhong, Zhu Cao, Qing-Hai Deng

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Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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7 authors.

Shao-Hua WuThe Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, China.

Fan GongThe Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, China.

Yang-Bo BiThe Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, China.

Yi-Ze BaiThe Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, China.

Cheng ZhongCollege of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China. zhongcheng@whu.edu.cn.

Zhu CaoThe Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, China. caozhu@shnu.edu.cn.ORCID http://orcid.org/0009-0002-3089-5477

Qing-Hai DengThe Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, China. qinghaideng@shnu.edu.cn.ORCID http://orcid.org/0000-0001-7793-1434

Funding

National Natural Science Foundation of China (National Science Foundation of China) 22371187, 22501184Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality) 22ZR1445200, 25ZR1402406

6 · The paper itself

Abstract

We report a regiodivergent strategy for the catalytic asymmetric synthesis of enantioenriched spirocyclic γ- and δ-lactams from a single cyclic alkyne-tethered β-ketoamide precursor. Critically, simply switching the catalyst system between Cu(I)/Pyrabox and Ni(II)/Box enables precise toggling of the cyclization between 5-exo-dig and 6-endo-dig modes, allowing direct and highly stereoselective access to either γ-lactam or δ-lactam spirocycles, each bearing a challenging quaternary spiro-stereocenter. The method exhibits broad functional group compatibility and allows for gram-scale synthesis. Mechanistic experiments and DFT calculations reveal that regioselectivity arises from the mode of metal coordination or the joint regulation by metal and ligand, whereas stereocontrol is governed by steric hindrance between the ligand and the substrate. This practical and atom-economical approach provides a powerful platform for the divergent synthesis of privileged spirocyclic pharmacophores.

Identifiers

PMID42665596

DOI10.1038/s41467-026-77228-2

PMCPMC13524950

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.