Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 4;15(46):19599-19603.
doi: 10.1039/d4sc05482b. eCollection 2024 Nov 27.

Pd/NHC sequentially catalyzed atroposelective synthesis of planar-chiral macrocycles

Gongming Yang  1 , Shangde Liu  1 , Shujie Ji  1 , Xingsen Wu  1 , Jian Wang  1
Affiliations

Pd/NHC sequentially catalyzed atroposelective synthesis of planar-chiral macrocycles

Gongming Yang et al. Chem Sci. .

Abstract

Planar-chiral macrocycles play a pivotal role in host-guest chemistry and drug discovery. However, compared with the synthesis of other types of chiral compounds, the asymmetric construction of planar-chiral macrocycles still remains a forbidding challenge. Herein, we report a sequential palladium and N-heterocyclic carbene catalysis to build planar-chiral macrocycles. This protocol features broad scope and good functional group tolerance, and allows a rapid assembling of planar-chiral macrocycles with excellent enantioselectivities.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Background and our design. (A) Representative planar-chiral macrocycle-containing molecules. (B) Asymmetric sequential catalysis. (C) Our design.
Fig. 2
Fig. 2. Scope of vinyl ethylene carbonate 2. aReaction conditions: see Table 1, entry 1. b12 h for the first step, 12 h for the second step. c24 h for the first step, 12 h for the second step.48 h. d36 h for the first step, 12 h for the second step.
Fig. 3
Fig. 3. Scope of aryl aldehyde 1. aReaction conditions: see Table 1, entry 1.
Fig. 4
Fig. 4. Determination of the racemization barrier. (A) Effect of temperature on the stability of macrocyclic planar chirality. (B) Plot for calculating the racemization barrier of 4o. (C) Racemization barriers of 3a, 4n and 4o.
Fig. 5
Fig. 5. Gram-synthesis and synthetic transformations. (A) Gram-scale synthesis. (B) Sonogashira coupling. (C) Epoxidation reaction.
Fig. 6
Fig. 6. Mechanistic studies: (a) Pd(PPh3)4 (2.5 mol%) and L1 (3 mol%) in toluene (1.0 mL), 2 h. (b) C1 (20 mol%), DQ (1.2 equiv.) and nBuN4OAc in toluene (4.0 mL), room temperature for 12 h.
See this image and copyright information in PMC

References

    1. Hassan Z. Spuling E. Knoll D. M. Lahann J. Bräse S. Chem. Soc. Rev. 2018;47:6947–6963. doi: 10.1039/C7CS00803A. - DOI - PubMed
    1. Ramaiah D. Neelakandan P. P. Nair A. K. Avirah R. R. Chem. Soc. Rev. 2010;39:4158–4168. doi: 10.1039/B920032K. - DOI - PubMed
    2. Liu Z. Nalluri S. K. M. Stoddart J. F. Chem. Soc. Rev. 2017;46:2459–2478. doi: 10.1039/C7CS00185A. - DOI - PubMed
    1. Quan M. Pang X.-Y. Jiang W. Angew. Chem., Int. Ed. 2022;61:e202201258. doi: 10.1002/anie.202201258. - DOI - PubMed
    2. Zhu H. Chen L. Sun B. Wang M. Li H. Stoddart J. F. Huang F. Nat. Rev. Chem. 2023;7:768–782. doi: 10.1038/s41570-023-00531-9. - DOI - PubMed
    1. Smolyar I. V. Yudin A. K. Nenajdenko V. G. Chem. Rev. 2019;119:10032–10240. doi: 10.1021/acs.chemrev.8b00789. - DOI - PubMed
    2. Swain J. A. Walker S. R. Calvert M. B. Brimble M. A. Nat. Prod. Rep. 2022;39:410–443. doi: 10.1039/D1NP00043H. - DOI - PubMed
    1. Plaza A. Keffer J. L. Bifulco G. Lloyd J. R. Bewley C. A. J. Am. Chem. Soc. 2010;132:9069–9077. doi: 10.1021/ja102100h. - DOI - PMC - PubMed
    2. Fullenkamp C. R. Hsu Y.-P. Quardokus E. M. Zhao G. Bewley C. A. VanNieuwenhze M. Sulikowski G. A. J. Am. Chem. Soc. 2020;142:16161–16166. doi: 10.1021/jacs.0c04917. - DOI - PMC - PubMed

LinkOut - more resources