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. 2024 Sep 4;146(35):24708-24715.
doi: 10.1021/jacs.4c09490. Epub 2024 Aug 20.

Rh(I)-Catalyzed Regio- and Enantioselective Ring Opening of Vinyl Cyclopropanes

Stephen J Webster  1 , László B Balázs  1 , F Wieland Goetzke  1 , Violeta Stojalnikova  1 , Ke Liu  1 , Kirsten E Christensen  1 , Harold W Mackenzie  1 , Stephen P Fletcher  1
Affiliations

Rh(I)-Catalyzed Regio- and Enantioselective Ring Opening of Vinyl Cyclopropanes

Stephen J Webster et al. J Am Chem Soc. .

Abstract

We describe a Rh(I) catalyzed asymmetric ring opening of racemic vinyl cyclopropanes using aryl boronic acids as C-nucleophiles. When ferrocene-based chiral bisphosphines are used as ligands, the products are obtained with regioselectivities typically 99:1 r.r. and ee's generally between 88 and 96%. A wide range of aryl boronic acids can be used, and the products can be converted into a variety of targets. Preliminary mechanistic studies indicate that Zn(OTf)2 plays a significant role in the reaction by promoting rhodium-ligand complex formation and accelerating the reaction. We expect this method and these mechanistic insights to be useful in the development of new asymmetric methods.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Asymmetric Ring Opening of D–A Cyclopropanes
Scheme 2
Scheme 2. Asymmetric Ring Opening of (±)-1,
Experiments performed on 0.5 mmol scale. Enantiomeric ratios were determined by SFC on a chiral nonracemic stationary phase. Enantiomeric ratios unable to be determined. Branched: linear regioselectivity determined by 1H NMR spectroscopic analysis of the crude reaction mixture. +Product was slightly (∼7%) impure. Absolute configurations were assigned by analogy to (S)-11 as determined by X-ray crystallography, which was derivatized from 3a.
Scheme 3
Scheme 3. Product Derivatization
Alkene, Grubbs II, DCM, 45 °C; BnCl, NaH, THF, r.t.; H2, [RhCl(PPh3)3], DCM, r.t.; NaOH, THF, r.t. then CDI, NaOH, THF; TFA, TFAA, 0 °C; m-CPBA, DCM, r.t.; HBPin, [RhCl(PPh3)3], THF, r.t.
Scheme 4
Scheme 4. Diverse Reactivity with D–A Cyclopropanes,,
Experiments performed on 0.5 mmol scale. Enantiomeric ratios were determined by SFC using a chiral nonracemic stationary phase. E/Z and d.r. ratios determined by 1H NMR spectroscopic analysis of the crude reaction mixture. +ee of one diastereomer
Scheme 5
Scheme 5. Kinetics of Ring-opening in Time
Scheme 6
Scheme 6. Effect of Zn(OTf)2 on Catalyst Mixture
Catalyst components are soluble under the conditions used.
Scheme 7
Scheme 7. Zn(OTf)2 Promoted Coordination
Catalyst components are soluble under the conditions used.
Scheme 8
Scheme 8. Rate Dependence on Zn(OTf)2
Scheme 9
Scheme 9. Proposed Mechanism
See this image and copyright information in PMC

References

    1. Pirenne V.; Muriel B.; Waser J. Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes. Chem. Rev. 2021, 121, 227–263. 10.1021/acs.chemrev.0c00109. - DOI - PubMed
    1. de Meijere A. Bonding Properties of Cyclopropane and Their Chemical Consequences. Angew. Chem., Int. Ed. 1979, 18, 809–826. 10.1002/anie.197908093. - DOI
    1. Kreft A.; Lücht A.; Grunenberg J.; Jones P. G.; Werz D. B. Kinetic Studies of Donor–Acceptor Cyclopropanes: The Influence of Structural and Electronic Properties on the Reactivity. Angew. Chem., Int. Ed. 2019, 58, 1955–1959. 10.1002/anie.201812880. - DOI - PubMed
    1. Xia Y.; Liu X.; Feng X. Asymmetric Catalytic Reactions of Donor–Acceptor Cyclopropanes. Angew. Chem., Int. Ed. 2021, 60, 9192–9204. 10.1002/anie.202006736. - DOI - PubMed
    1. Ivanova O. A.; Trushkov I. V. Donor-Acceptor Cyclopropanes in the Synthesis of Carbocycles. Chem. Rec. 2019, 19, 2189–2208. 10.1002/tcr.201800166. - DOI - PubMed

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