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Liu et al. Chem Synth 2023;3:22 https://dx.doi.org/10.20517/cs.2023.18 Page 5 of 9

[a]
Figure 2. Reaction Scope . [a] Reaction conditions:1a (0.05 mmol), DDQ (0.55 mmol), H1 (0.075 mmol), catalyst (10 mol%), solvent
1
(1.0 mL). The yield was determined to be > 95% in all the cases by H NMR and TLC analyses of the crude reaction mixture; ee value
was determined by chiral HPLC analysis. [b] Run with 0.5 mol% of catalyst. Solvent (0.18 mL, c = 0.28 M). [c] Run for 36 h. [d] Run at -
o
10 C, 1a (0.4 mmol), DDQ (0.44 mmol), H1 (0.6 mmol), solvent (1.44 mL), 96 h.
excess, demonstrating the compatibility of this mild protocol to heterocycles. In these examples, an ortho-
methoxy group was present in one of the aryl rings to provide differentiation between the other arene. It is
worth noting that other directing groups, such as fluorine and benzyl ether, could also serve the same
purpose . More drastically, discrimination of these two arenes by steric hindrance is also possible. For
[55]
example, a methyl or ethyl group at the ortho-position also led to good enantioselectivity. Ortho-halogen (Cl
or Br) also provided good levels of differentiation. This is noteworthy since these halide groups can be easily
converted to many other functionalities. Interestingly, if both ortho-OMe and ortho-F are present in the two
arenes, effective discrimination was also observed. Notably, the absolute stereochemistry of product 2f was
confirmed by X-ray crystallography.

To further demonstrate the robustness of this process, we carried out a gram-scale reaction of 1a. Under the
standard conditions, the desired deracemization product was obtained in 96% yield and 98% ee [Scheme 2].
The ortho-methoxy group in product 2a could also be deprotected to form a free hydroxyl group without
erosion in enantiomeric excess. Based on our previous work , this bis(phenol) 3a could be further
[65]
converted to spirocyclic dienone 4 in the presence of PhI(OAc) without erosion in its ee value.
2
CONCLUSIONS
In summary, we have developed the first deracemization approach for efficient access to enantioenriched
triarylmethanes, a type of useful structure in medicinal chemistry. In contrast to the well-established
deracemization processes for monoaryl- and diaryl-substituted carbon stereogenic centers, limited success
has been achieved previously for triaryl-substituted ones. Specifically, herein a redox strategy involving the
initial oxidation of racemic triarylmethanes followed by asymmetric reduction has been achieved in a one-
pot fashion. With suitable substitution on the arenes, this process proceeds through the key para-quinone
methide intermediate. Chiral phosphoric acids have shown excellent capability in catalyzing this process.
The reaction features mild conditions and low catalyst loading. This process provided a diverse set of highly
enantioenriched triarylmethanes with high efficiency and excellent enantioselectivity. Notably, diverse ortho