Organophotoredox-catalyzed semipinacol rearrangement via radical-polar crossover

1.

2.

3.

4.

Methods

The reaction to produce 2a in Table 1, entry 1 is representative. In a glovebox,

to an oven-dried vial with a stirring bar was added PTH1 (3.3 mg, 0.01 mmol),

lithium tetrafluoroborate (0.9 mg, 0.01 mmol) and β-hydroxyester 1a (81.9 mg,

0.2 mmol). Ethyl acetate (600 µL) was added to the reaction mixture. The reaction

was stirred and irradiated with a 34 W blue LED (0.5 cm away) with a cooling fan

to keep the temperature around 40 °C. After 24 h, the reaction was quenched by

0.5 M NaOH aq. solution (1.5 mL). The aqueous layer was extracted three times

with dichloromethane (500 μL × 3) and then the combined organic layer was dried

over Na2SO4 and filtered. After volatiles were removed under reduced pressure,

purification by flash column chromatography on silica gel (100:0–90:10, hexane/

EtOAc) gave the rearrangement product 2a (39.7 mg, 0.18 mmol, 91% yield).

The reaction to produce 6aa in Fig. 3 is representative. In a glovebox, to an

oven-dried vial with a stirring bar was added PTH1 (6.5 mg, 0.02 mmol), sodium

perchlorate monohydrate (2.8 mg, 0.02 mmol) and allylic alcohol 4a (47.7 mg,

0.2 mmol). Dichloromethane (562.5 µL), water (37.5 µL) and ethyl bromomalonate

(50.5 µL, 0.3 mmol) were added to the reaction mixture. The reaction was stirred and

irradiated with a 34 W blue LED (0.5 cm away) with a cooling fan to keep the

temperature around 40 °C. After 20 h, the reaction was quenched by sat. NH4Cl aq.

solution (1.5 mL). The aqueous layer was extracted three times with dichloromethane

(500 μL × 3), and then the combined organic layer was dried over Na2SO4 and

filtered. After volatiles were removed under reduced pressure, purification by flash

column chromatography on silica gel (Biotage Selekt, 99:1–90:10, hexane/EtOAc)

gave the rearrangement product 6aa (66.6 mg, 0.17 mmol, 84% yield).

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

Data availability

The authors declare that the data supporting the findings of this study are available

within the paper or its Supplementary Information files and from the corresponding

author upon request.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant Number JP21H04681 to Scientific

Research (A), JP21K15223 to Grant-in-Aid for Young Scientists, JSPS KAKENHI Grant

Number JP17H06449 (Hybrid Catalysis), JSPS KAKENHI Grant Number JP21H05388

(Dynamic Exciton), Taisho Pharmaceutical Award in Synthetic Organic Chemistry,

Japan, and JST, PRESTO Grant Number JPMJPR19T2.

Author contributions

T.K., K.N., and H.O. designed, performed and analysed the experiments. K.N. and H.O.

co-wrote the manuscript. All authors contributed to discussions.

Competing interests

The authors declare no competing interests.

Additional information

Supplementary information The online version contains supplementary material

available at https://doi.org/10.1038/s41467-022-30395-4.

Correspondence and requests for materials should be addressed to Kazunori Nagao or

Hirohisa Ohmiya.

Peer review information Nature Communications thanks Guo-Qiang Xu, Shu-Yu Zhang

and the other, anonymous, reviewer(s) for their contribution to the peer review of

this work.

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