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. 2021 Jul 29;12(35):11793-11798.
doi: 10.1039/d1sc03324g. eCollection 2021 Sep 15.

Organocatalytic asymmetric formal oxidative coupling for the construction of all-aryl quaternary stereocenters

Zhiyang Li  1   2 , Yichen Li  3 , Xingguang Li  1   4 , Mandi Wu  3 , Ming-Liang He  3 , Jianwei Sun  1   2   4
Affiliations

Organocatalytic asymmetric formal oxidative coupling for the construction of all-aryl quaternary stereocenters

Zhiyang Li et al. Chem Sci. .

Abstract

A new catalytic asymmetric formal cross dehydrogenative coupling process for the construction of all-aryl quaternary stereocenters is disclosed, which provides access to rarely explored chiral tetraarylmethanes with excellent enantioselectivity. The suitable oxidation conditions and the hydrogen-bond-based organocatalysis have enabled efficient intermolecular C-C bond formation in an overwhelmingly crowded environment under mild conditions. para-Quinone methides bearing an ortho-directing group serve as the key intermediate. The precise loading of DDQ is critical to the high enantioselectivity. The chiral products have also been demonstrated as promising antiviral agents.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Catalytic asymmetric synthesis of chiral tetraarylmethanes.
Scheme 2
Scheme 2. Reaction scope. Reaction scale: 1 (0.25 mmol), DDQ (0.25 mmol), DCE (5.0 mL), rt, 5 h; then 3 (0.50 mmol), (R)-A5 (18.8 μmmol), 0 °C, 3 h. Isolated yield is provided. The ee value was determined by chiral HPLC analysis. aRun at −20 °C for 12 h after catalyst addition. bRun at rt for 24 h after catalyst addition.
Scheme 3
Scheme 3. Product transformations. [a] Tf2O, Et3N, DCM, 0 °C to rt; [b] PhB(OH)2, Pd(OAc)2, BrettPhos, K3PO4, tBuOH, 85 °C; [c] Et3SiH, Pd(OAc)2, dppp, DMF, 60 °C; [d] AllylBpin, Pd(OAc)2, BrettPhos, K3PO4, tBuOH, 85 °C.
Scheme 4
Scheme 4. Mechanistic study.
Fig. 1
Fig. 1. The antiviral effects examined by CPE assay and quantitation of viral RNA copies in the secreted virions. RD cells were treated with the indicated compounds and infected with EV-A71 at a MOI of 0.1, and the cell morphology was observed using a phase-contrast microscope 24 h post infection. The viral RNA genome copy number was determined by RT-qPCR.
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