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. 2016 Jul 1;18(13):3286-9.
doi: 10.1021/acs.orglett.6b01580. Epub 2016 Jun 16.

Modular, Catalytic Enantioselective Construction of Quaternary Carbon Stereocenters by Sequential Cross-Coupling Reactions

Bowman Potter  1 , Emma K Edelstein  1 , James P Morken  1
Affiliations

Modular, Catalytic Enantioselective Construction of Quaternary Carbon Stereocenters by Sequential Cross-Coupling Reactions

Bowman Potter et al. Org Lett. .

Abstract

The catalytic Suzuki-Miyaura cross-coupling with chiral γ,γ-disubstituted allylboronates in the presence of RuPhos ligand occurs with high regioselectivity and enantiospecificity, furnishing nonracemic compounds with quaternary centers. Mechanistic experiments suggest that the reaction occurs by transmetalation with allyl migration, followed by rapid reductive elimination.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1
Sequential Cross-Coupling Approach to the Asymmetric Construction of Quaternary Carbon Stereoenters
Scheme 2
Scheme 2
Survey of Substrates for Pd/RuPhos Catalyzed Cross-Coupling of Allylboronates and Electrophiles.a aReactions conducted on 0.1 mmol scale at 60 °C for aryl electrophiles or 50 °C for alkenyl electrophiles. bYield is isolated yield of purified material. Regioisomer ratios were determined by 1H NMR analysis, enantiospecificity determined by chiral SFC analysis. cEmployed 3.0 equiv chloropyridine•HCl and 7.5 equiv KOH.
Scheme 3
Scheme 3
Sequential Cross-Coupling to Furnish Enantiomeric Products from the Same Enantiomer of Catalyst.
Scheme 4
Scheme 4
Single-Flask Sequential Cross-Couplings
Scheme 5
Scheme 5
Catalytic Synthesis of Chiral Hydrocarbon 38.
Scheme 6
Scheme 6
Mechanistic Experiments and the Origin of Regioselectivity
See this image and copyright information in PMC

References

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    1. For a review of stereospecific cross-coupling, see: Cherney AH, Kadunce NT, Reisman SE. Chem Rev. 2015;115:9587.

    1. Zhang P, Le H, Kyne RE, Morken JP. J Am Chem Soc. 2011;133:9716. - PMC - PubMed
    2. Ardolino MJ, Morken JP. J Am Chem Soc. 2014;136:7092. - PMC - PubMed

    1. For an alternative synthesis of nonracemic asymmetric quaternary carbon centers from organoboronates, see: Bonet A, Odachowski M, Leonori D, Essafi S, Aggarwal VK. Nat Chem. 2014;6:584.Llaveria J, Leonori D, Aggarwal VK. J Am Chem Soc. 2015;137:10958.

    1. Potter B, Szymaniak AA, Edelstein EK, Morken JP. J Am Chem Soc. 2014;136:17918. - PMC - PubMed
    2. Sun C, Potter B, Morken JP. J Am Chem Soc. 2014;136:6534. - PMC - PubMed

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