Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec 17;86(24):17762-17773.
doi: 10.1021/acs.joc.1c01769. Epub 2021 Dec 2.

Probing Catalyst Function - Electronic Modulation of Chiral Polyborate Anionic Catalysts

Wynter E G Osminski  1 , Zhenjie Lu  1 , Wenjun Zhao  1 , Aliakbar Mohammadlou  1 , Xiaopeng Yin  1 , Emily C Matthews  1 , Virginia M Canestraight  1 , Richard J Staples  1 , Connor J Allen  2 , Jennifer S Hirschi  2 , William D Wulff  1
Affiliations

Probing Catalyst Function - Electronic Modulation of Chiral Polyborate Anionic Catalysts

Wynter E G Osminski et al. J Org Chem. .

Abstract

Boroxinate complexes of VAPOL and VANOL are a chiral anionic platform that can serve as a versatile staging arena for asymmetric catalysis. The structural underpinning of the platform is a chiral polyborate core that covalently links together alcohols (or phenols) and vaulted biaryl ligands. The polyborate platform is assembled in situ by the substrate of the reaction, and thus a multiplex of chiral catalysts can be rapidly assembled from various alcohols (or phenols) and bis-phenol ligands for screening of catalyst activity. In the present study, variations in the steric and electronic properties of the phenol/alcohol component of the boroxinate catalyst are probed to reveal their effects on the asymmetric induction in the catalytic asymmetric aziridination reaction. A Hammett study is consistent with a mechanism in which the two substrates are hydrogen-bonded to the boroxinate core in the enantiogenic step. The results of the Hammett study are supported by a computational study in which it is found that the H-O distance of the protonated imine hydrogen bonded to the anionic boroxinate core decreases with an increase in the electron releasing ability of the phenol unit incorporated into the boroxinate. The results are not consistent with a mechanism in which the boroxinate catalyst functions as a Lewis acid and activates the imine by a Lewis acid/Lewis base interaction.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Correlation between enantiomer ratio in the formation of aziridine 22a and σp− for substituents in VANOL boroxinate catalyst 4.
Figure 2.
Figure 2.
Correlation between enantiomer ratio in the formation of aziridine 23a and σp− for substituents in VAPOL boroxinate catalyst 4.
Figure 3.
Figure 3.
Correlation between enantiomer ratio in the formation of aziridine 23b and σp− for substituents in VANOL boroxinate catalyst 4.
Figure 4.
Figure 4.
Correlation between enantiomer ratio in the formation of aziridine 23b and σp− for substituents in VAPOL boroxinate catalyst 2.
Figure 5.
Figure 5.
Boroxinate H-imine complex with H-bonding of the iminium to O-2.
Figure 6.
Figure 6.
Electrostatic potential slice maps of the Boroxinate-H-Imine complexes with the highest (R3 = Cy, ee = 96%) and lowest (R3 = 4-NO2Ph, ee = 68%) enantioselectivities for catalyst derivatives bearing phenyl substituents on the iminium complex in the plane of the NH···O interaction; red areas are stabilizing for positive charges, blue areas are stabilizing for negative charges. Bond distances are shown in angstroms, and the atoms from the catalyst backbone (this is the blue area in the bottom right-hand quadrant of both structures) have been removed for clarity.
Scheme 1.
Scheme 1.
Boroxinate Catalysts from VAPOL and VANOL
Scheme 2.
Scheme 2.
Four Methods for the Preparation of Boroxinate Catalysts
Scheme 3.
Scheme 3.
Summary of the Mechanism of Aziridine Formation
Scheme 4.
Scheme 4.
Brønsted Acid versus Lewis acid Catalyst for the Borate Ester of BINOL
Scheme 5.
Scheme 5.
Brønsted versus Lewis Acid Catalysts for the Boroxinate Catalyst System
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Hu G; Gupta AK; Huang RH; Mukherjee M; Wulff WD Substrate-Induced Covalent Assembly of a Chemzyme and Crystallographic Characterization of a Chemzyme-substrate Complex. J. Am. Chem. Soc. 2010, 132, 14669–14675. - PubMed
    1. Zhang Y; Desai A; Lu Z; Hu G; Ding Z; Wulff WD Asymmetric Catalytic Aziridination with Borate Catalysts Derived from the VANOL and VAPOL Ligands – Scope and Mechanistic Studies. Chem. - Eur. J. 2008, 14, 3785–3803. - PubMed
    1. Vetticatt MJ; Desai AA; Wulff WD How the Binding of Substrates to a Chiral Polyborate Counterion Governs Diastereoselection in an Aziridination Reaction: H-Bonds in Equipoise. J. Am. Chem. Soc. 2010, 132, 13104–13107. - PubMed
    1. Guan Y; Lu Z; Yin X; Mohammadlou A; Staples RJ; Wulff WD Catalytic Asymmetric Aziridination of Benzhydryl Imines and Diazoacetate Esters with BOROX Catalysts from 3,3′-Disubstituted VANOL Ligands. Synthesis 2020, 52, 2073–2091.
    1. Kaufmann D; Boese R A Borate Propeller Compound as Chiral Catalyst for an Asymmetrically Induced Diels-Alder Reaction. Angew. Chem., Int. Ed. Engl. 1990, 29, 545–546.
    2. Thormeier S; Carboni B; Kaufmann DE Chiral boronates–versatile reagents in asymmetric synthesis. J. Organomet. Chem. 2002, 657, 136–145. For a review, see:
    3. Dimitrijevic A; Taylor MS Organoboron Acids and Their Derivatives as Catalysts for Organic Synthesis. ACS Catal. 2013, 3, 945.

Publication types