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. 2020 Mar 18;142(11):5017-5023.
doi: 10.1021/jacs.0c01330. Epub 2020 Mar 4.

Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes

Amberly B Sanford  1 , Taylor A Thane  1 , Tristan M McGinnis  1 , Pan-Pan Chen  2 , Xin Hong  2 , Elizabeth R Jarvo  1
Affiliations

Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes

Amberly B Sanford et al. J Am Chem Soc. .

Abstract

Cross-electrophile coupling reactions of two Csp3-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.

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Figures

Figure 1.
Figure 1.
Comparison of DFT-computed barriers for Ni(0)-catalyzed C–I oxidative addition, employing dppm as the ligand. Free energies in toluene are in kcal/mol and were calculated under the M06/def2-TZVPP-SMD(toluene)//B3LYP-D3(BJ)/def2-SVP-SMD(toluene) level of theory.
Scheme 1.
Scheme 1.
Nickel-Catalyzed XC and XEC Reactions of Alkyl Sulfates and Sulfonates
Scheme 2.
Scheme 2.
Isolated yields of reaction products. aYield determined by 1H NMR based on comparison to PhTMS as internal standard. b3.0 equiv of MeMgI
Scheme 3.
Scheme 3.
Competition experiments.
Scheme 4.
Scheme 4.
Stereoconvergent XEC reactions
Scheme 5.
Scheme 5.
1,2-Disubstituted cyclopropanes aYield determined by 1H NMR based on comparison to PhTMS as internal standard. bReaction stirred at 0 °C
Scheme 6.
Scheme 6.
Enantioenriched 1,2-disubstituted cyclopropanes aYield determined by 1H NMR based on comparison to PhTMS as internal standard
See this image and copyright information in PMC

References

    1. Biswas S; Weix DJ Mechanism and Selectivity in Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Halides with Alkyl Halides. J. Am. Chem. Soc 2013, 135, 16192–16197. - PMC - PubMed
    2. Everson DA; Weix DJ Cross-Electrophile Coupling: Principles of Reactivity and Selectivity. J. Org. Chem 2014, 79, 4793–4798. - PMC - PubMed
    3. Weix DJ Methods and Mechanisms for Cross-Electrophile Coupling of Csp2 Halides with Alkyl Electrophiles. Acc. Chem. Res 2015, 48, 1767–1775. - PMC - PubMed
    4. Knappke CEI; Grupe S; Gärtner D; Corpet M; Gosmini C; Jacobi von Wangelin A Reductive Cross-Coupling Reactions between Two Electrophiles. Chem. Eur. J 2014, 20, 6828–6842. - PubMed
    5. Wang X; Dai Y; Gong H Nickel-Catalyzed Reductive Couplings. Top. Curr. Chem 2016, 374, 43. - PubMed
    1. For an example, see: Everson DA; Jones BA; Weix DJ Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides. J. Am. Chem. Soc 2012, 134, 6146–6159. - PMC - PubMed
    1. For a recent discussion and solution in the context of vinyl electrophiles, see: Olivares AM; Weix DJ Multimetallic Ni- and Pd-Catalyzed Cross-Electrophile Coupling to form Highly Substituted 1,3-Dienes. J. Am. Chem. Soc 2018, 140, 2446–2449. - PMC - PubMed
    1. Lucas EL; Jarvo ER Stereospecific and Stereoconvergent Cross-Couplings Between Alkyl Electrophiles. Nat. Rev. Chem 2017, 1, 0065.
    1. Tollefson EJ; Erickson LW Jarvo ER Stereospecific Intramolecular Reductive Cross-Electrophile Coupling Reactions for Cyclopropane Synthesis. J. Am. Chem. Soc 2015, 137, 9760. - PubMed
    2. Erickson LW Lucas EL; Tollefson EJ; Jarvo ER Nickel-Catalyzed Cross-Electrophile Coupling of Alkyl Fluorides: Stereospecific Synthesis of Vinylcyclopropanes. J. Am. Chem. Soc 2016, 138, 14006–14011. - PubMed
    3. Konev MO; Hanna LE; Jarvo ER Intra- and Intermolecular Nickel-Catalyzed Reductive Cross-Electrophile Coupling Reactions of Benzylic Esters with Aryl Halides. Angew. Chem. Int. Ed 2006, 55, 6730–6733. - PubMed

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