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. 2023 Sep 22;25(37):6897-6901.
doi: 10.1021/acs.orglett.3c02627. Epub 2023 Sep 11.

Cu-Catalyzed Enantioselective Protoboration of 2,3-Disubstituted 1,3-Dienes

Sensheng Liu  1 , Yangbin Liu  1 , Arthur Flaget  1 , Cheng Zhang  1 , Clément Mazet  1
Affiliations

Cu-Catalyzed Enantioselective Protoboration of 2,3-Disubstituted 1,3-Dienes

Sensheng Liu et al. Org Lett. .

Abstract

A Cu-catalyzed regio- and enantioselective protoboration of 2,3-disubstituted 1,3-dienes is described. The protocol operates under mild conditions and is applicable to symmetrically and unsymmetrically substituted dienes, providing access to homoallylic boronates in consistently high yield, regioselectivity, and enantiomeric ratio. Preliminary investigations point to a complex mechanism.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Cu-catalyzed selective borofunctionalization of 1,3-dienes. (B–E) Cu-catalyzed enantioselective protoboration of: (B) cyclic 1,3-dienes; (C) branched 1,3-dienes; (D) linear 1,3-dienes; (E) 2,4-disubstituted 1,3-dienes. (F) This work: Cu-catalyzed enantioselective protoboration of 2,3-disubstituted 1,3-dienes.
Figure 2
Figure 2
Sequential protoboration/oxidation of symmetrical 2,3-disubstituted 1,3-dienes. Reaction conditions: 1a–k (0.5 mmol), B2pin2 (0.5 mmol). Regioselectivity assessed by 1H NMR before oxidation. Yield after oxidation to 2′. Er determined after oxidation by HPLC. Absolute configuration determined by analogy with a known compound.
Figure 3
Figure 3
Sequential protoboration/oxidation of unsymmetrical 2,3-disubstituted 1,3-dienes. Reaction conditions: 1l–t (0.5 mmol), B2pin2 (0.5 mmol). Regioselectivity assessed by 1H NMR before oxidation. Yield after oxidation to 2′. Er was determined after oxidation by HPLC. Absolute configuration was determined by analogy with a known compound.aCombined yield.
Figure 4
Figure 4
Large scale experiment using 1d. Er was measured by HPLC after oxidation. Recrystallization was performed using MeOH/CHCl3 (10:1).
Figure 5
Figure 5
(A) Kinetic isotope effect. (B) Influence of the structure of the protonation agent. (C) Variable time normalization analyses. All data are the average of at least two experiments. Er was measured by HPLC.
Figure 6
Figure 6
Proposed catalytic cycle.
See this image and copyright information in PMC

References

    1. Semba K.; Fujihara T.; Terao J.; Tsuji Y. Copper-Catalyzed Borylative Transformations of Non-Polar Carbon–Carbon Unsaturated Compounds Employing Borylcopper as an Active Catalyst Species. Tetrahedron 2015, 71, 2183–2197. 10.1016/j.tet.2015.02.027. - DOI
    2. Perry G. J. P.; Jia T.; Procter D. J. Copper-Catalyzed Functionalization of 1,3-Dienes: Hydrofunctionalization, Borofunctionalization, and Difunctionalization. ACS Catal. 2020, 10, 1485–1499. 10.1021/acscatal.9b04767. - DOI
    3. Whyte A.; Torelli A.; Mirabi B.; Zhang A.; Lautens M. Copper-Catalyzed Borylative Difunctionalization of π-Systems. ACS Catal. 2020, 10, 11578–11622. 10.1021/acscatal.0c02758. - DOI
    1. Sasaki Y.; Zhong C.; Sawamura M.; Ito H. Copper (I)-Catalyzed Asymmetric Monoborylation of 1,3-Dienes: Synthesis of Enantioenriched Cyclic Homoallyl-and Allylboronates. J. Am. Chem. Soc. 2010, 132, 1226–1227. 10.1021/ja909640b. - DOI - PubMed
    2. Liu Y.; Fiorito D.; Mazet C. Copper-Catalyzed Enantioselective 1,2-Borylation of 1,3-Dienes. Chem. Sci. 2018, 9, 5284–5288. 10.1039/C8SC01538D. - DOI - PMC - PubMed
    3. Guan Q.; Ji Y.; Zhao Q.; Zhang C. Copper-Catalyzed Highly Enantioselective 1,4-Protoboration of Terminal 1,3-Dienes. CCS Chem. 2022, 4, 1545–1556. 10.31635/ccschem.021.202100947. - DOI
    4. Xu R. S.; Rohde L. N. Jr.; Diver S. T. Regioselective Cu-Catalyzed Hydroboration of 1,3-Disubstituted-1,3-Dienes: Functionalization of Conjugated Dienes Readily Accessible through Ene-Yne Metathesis. ACS Catal. 2022, 12, 6434–6443. 10.1021/acscatal.2c01190. - DOI
    1. Fehr C. Enantioselective Protonation of Enolates and Enols. Angew. Chem., Int. Ed. 1996, 35, 2566–2587. 10.1002/anie.199625661. - DOI
    2. Mohr J. T.; Hong A. Y.; Stoltz B. M. Enantioselective Protonation. Nat. Chem. 2009, 1, 359–369. 10.1038/nchem.297. - DOI - PMC - PubMed
    3. Oudeyer S.; Briere J.-F.; Levacher V. Progress in Catalytic Asymmetric Protonation. Eur. J. Org. Chem. 2014, 2014, 6103–6119. 10.1002/ejoc.201402213. - DOI
    1. Palais L.; Mikhel I. S.; Bournaud C.; Micouin L.; Falciola C. A.; Augustin M. V.; Rosset S.; Bernardinelli G.; Alexakis A. SimplePhos Monodentate Ligands: Synthesis and Application in Copper-Catalyzed Reactions. Angew. Chem., Int. Ed. 2007, 119, 7606–7609. 10.1002/ange.200702186. - DOI - PubMed
    2. Fiorito D.; Liu Y. B.; Besnard C.; Mazet C. Direct Access to Chiral Secondary Amides by Copper-Catalyzed Borylative Carboxamidation of Vinylarenes with Isocyanates. J. Am. Chem. Soc. 2020, 142, 623–632. 10.1021/jacs.9b12297. - DOI - PubMed
    1. Jarava-Barrera C.; Parra A.; López A.; Cruz-Acosta F.; Collado-Sanz D.; Cárdenas D. J.; Tortosa M. Copper-Catalyzed Borylative Aromatization of p-Quinone Methides: Enantioselective Synthesis of Dibenzylic Boronates. ACS Catal. 2016, 6, 442–446. 10.1021/acscatal.5b02742. - DOI - PMC - PubMed
    2. Kubota K.; Watanabe Y.; Hayama K.; Ito H. Enantioselective Synthesis of Chiral Piperidines via the Stepwise Dearomatization/Borylation of Pyridines. J. Am. Chem. Soc. 2016, 138, 4338–4341. 10.1021/jacs.6b01375. - DOI - PubMed
    3. Desfeux C.; Besnard C.; Mazet C. [n]Dendralenes as a Platform for Selective Catalysis: Ligand-Controlled Cu-Catalyzed Chemo-, Regio-, and Enantioselective Borylations. Org. Lett. 2020, 22, 8181–8187. 10.1021/acs.orglett.0c01892. - DOI - PubMed
    4. Wu J.; Wu H.; Li X.; Liu X.; Zhao Q.; Huang G.; Zhang C. Copper-Catalyzed Highly Selective Protoboration of CF3-Containing 1,3-Dienes. Angew. Chem., Int. Ed. 2021, 133, 20539–20545. 10.1002/ange.202105896. - DOI - PubMed