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. 2024 Dec 13;26(49):10553-10558.
doi: 10.1021/acs.orglett.4c03943. Epub 2024 Nov 28.

Metal-Catalyzed Hydrogen Atom Transfer (MHAT) Hydroalkylation with Electron-Deficient Alkynes

Laura G Rodríguez  1 , Josep Bonjoch  1 , Ben Bradshaw  1
Affiliations

Metal-Catalyzed Hydrogen Atom Transfer (MHAT) Hydroalkylation with Electron-Deficient Alkynes

Laura G Rodríguez et al. Org Lett. .

Abstract

We present a novel strategy for olefin construction via the reductive coupling of electron-neutral alkenes with electron-deficient alkynes under metal-catalyzed hydrogen atom transfer conditions. This methodology provides selective access to both trans and the more challenging-to-synthesize cis isomers and permits the olefin to be installed next to sterically hindered centers, key factors in the synthesis of biologically active compounds. The reaction exhibits broad functional group tolerance and proceeds under mild, nontoxic conditions with high atom efficiency.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Giese addition to electron-deficient alkenes and alkynes.
Scheme 1
Scheme 1. Scope of the Coupling of Unbiased Alkenes to Electron-Deficient Alkynes
3.0 equiv of donor were used. 5.0 equiv of donor and 0.5 equiv of PhSiH3 were used The cis product spontaneously isomerized, so the mixture was directly subjected to isomerization conditions. 1.0 equiv of NaHCO3 was added. Conditions: 0.20 equiv of Lindlar catalyst, 0.15 equiv of quinoline, MeOH (0.12 M), 25 °C, 24 h. Conditions: 1.0 equiv of Fe(acac)3, 2.5 equiv of PhSiH3, EtOH [0.10 M], 60 °C, 16 h.
Figure 2
Figure 2
Proposed mechanism and supporting studies.
See this image and copyright information in PMC

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References

    1. Silvi M.; Aggarwal V. K. Radical Addition to Strained σ-Bonds Enables the Stereocontrolled Synthesis of Cyclobutyl Boronic Esters. J. Am. Chem. Soc. 2019, 141, 9511–9515. 10.1021/jacs.9b03653. - DOI - PubMed
    2. Yang B.; Lu S.; Wang Y.; Zhu S. Diverse synthesis of C2-linked functionalized molecules via molecular glue strategy with acetylene. Nat. Commun. 2022, 13, 1858.10.1038/s41467-022-29556-2. - DOI - PMC - PubMed
    3. Paul S.; Filippini D.; Silvi M. Polarity Transduction Enables the Formal Electronically Mismatched Radical Addition to Alkenes. J. Am. Chem. Soc. 2023, 145, 2773–2778. 10.1021/jacs.2c12699. - DOI - PMC - PubMed
    1. Garwood J. J. A.; Chen A. D.; Nagib D. A. Radical Polarity. J. Am. Chem. Soc. 2024, 146, 28034–28059. - PubMed
    1. Giese B. Formation of CC Bonds by Addition of Free Radicals to Alkenes. Angew. Chem., Int. Ed. Engl. 1983, 22, 753–764. 10.1002/anie.198307531. - DOI
    2. Srikanth G. S. C.; Castle S. L. Advances in radical conjugate additions. Tetrahedron. 2005, 61, 10377–10441. 10.1016/j.tet.2005.07.077. - DOI
    3. Kitcatt D. M.; Nicolle S.; Lee A. L. Direct decarboxylative Giese reactions. Chem. Soc. Rev. 2022, 51, 1415–1453. 10.1039/D1CS01168E. - DOI - PubMed
    1. Dieter R. K.; Alexander C. W.; Nice L. E. Conjugate Addition Reactions of α-Aminoalkylcuprates with α,β-Enones and Enals. Tetrahedron. 2000, 56, 2767–2778. 10.1016/S0040-4020(00)00130-7. - DOI
    2. Yan X.; Harutyunyan S. R. Catalytic enantioselective addition of organometallics to unprotected carboxylic acids. Nat. Commun. 2019, 10, 3402.10.1038/s41467-019-11345-z. - DOI - PMC - PubMed
    1. Young I. S.; Baran P. S. Protecting-group-free synthesis as an opportunity for invention. Nat. Chem. 2009, 1, 193–205. 10.1038/nchem.216. - DOI - PubMed

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