Enantiodivergent epoxidation of alkenes with a photoswitchable phosphate manganese-salen complex

The development of enantiodivergent catalysts capable of preparing both enantiomeric products from one substrate in a controlled fashion is challenging. Introducing a switching function into the catalyst can address this challenge, allowing the chiral reaction environment to reversibly change during catalysis. Here we report a photoswitchable phosphate ligand, derived from 2,2’-biphenol, which axially coordinates as the counter ion to an achiral manganese(III) salen catalyst, providing the latter with the ability to switch stereoselectivity in the epoxidation of alkenes. The enantiomers of the chiral ligand exist as a pair of pseudo-enantiomers, which can be interconverted by irradiation with light of different wavelengths. The opposite axial chirality of these pseudo-enantiomers is efficiently transferred to the manganese(III) salen catalyst. With this switchable supramolecular catalyst, the enantioselectivity of the epoxidation of a variety of alkenes can be controlled, resulting in opposite enantiomeric excesses of the epoxide products. This transfer of chirality from a photoswitchable anionic ligand to a metal complex broadens the scope of supramolecular catalysts.

Spectral data were in agreement with literature values. S1

Synthesis of catalysts
The synthetic procedure was based on a previously reported protocol. S2 Rac-Mn2.
Manganese(III) salen complex Mn15 (29.0 mg, 50 µmol, 1.0 equiv) and phosphoric acid Rac-1 (37.8 mg, 51 µmol, 1.02 equiv) were dissolved in acetone (0.40 mL). Then, aqueous 2.5M NaOH (20.4 µL, 51 µmol, 1.02 equiv) was added and the resulting mixture was stirred for 4 hours in the dark. The solvent was removed in vacuo to afford a brown solid. This brown solid was dissolved in dry CH2Cl2 (6 mL) leaving behind a white precipitate of NaCl. The solution was separated from the precipitate, and the solvent was removed in vacuo to afford again a brown solid. This dissolution, separation, and evaporation process was repeated two more times to ensure complete removal of NaCl. The thus obtained brown material was dried under high vacuum (<1 mbar) for 2 days to afford the racemic catalyst Rac-Mn2 (61.8 mg, 48 μmol, 96%) as a brown solid.

General epoxidation procedure
A pre-dried Schlenk finger was charged with racemic or enantiopure catalyst Mn2 (3.2 mg, 2.5 mol%). The Schlenk finger was evacuated and backfilled with argon (3×). Then, olefin substrate (0.10 mmol, 1.0 equiv) and dry benzene (1.9 mL) were added and the resulting brown solution was stirred at 20 °C for 5 minutes. Subsequently, iodosylbenzene (26.4 mg, 0.12 mmol, 1.2 equiv) was added in one portion. The resulting mixture was stirred for 16 hours in the dark under an argon atmosphere. Thereafter, the solvent was removed in vacuo and the crude product was purified by preparative TLC (eluent: EtOAc/n-heptane, 1:3, v/v) to afford the isolated epoxide product. Enantiomeric excess values were determined by chiral HPLC analysis.

Resolution of enantiomers of phosphoric acid Rac-1 2.1 Analytical chiral HPLC separation data for compound Rac-1
The sample was dissolved in dichloromethane, injected onto the chiral column, and detected with an UV detector at 254 nm and with a circular dichroism detector at 254 nm. The flow-rate was 1 mL/min.
• First fraction: 720 mg of the first eluted enantiomer with ee > 99 %.
Supplementary Figure 2. Chiral HPLC chromatogram of the first eluted enantiomer of compound 1.

RT [min]
Area

Optical rotations
Optical rotations were measured on a Jasco P-2000 polarimeter with a halogen lamp (589, 578 and 546 nm), in a 10 cm cell, thermostated at 25°C with a Peltier controlled cell holder.

Electronic Circular Dichroism
ECD and UV spectra were measured on a JASCO J-815 spectrometer equipped with a JASCO Peltier cell holder PTC-423 to maintain the temperature at 25.0 ± 0.2°C. A CD quartz cell of 1 mm of optical pathlength was used. The CD spectrometer was purged with nitrogen before recording each spectrum, which was baseline subtracted. The baseline was always measured for the same solvent and in the same cell as the samples. The spectra are presented without smoothing and further data processing. Acquisition parameters: 0.1 nm as intervals, scanning speed 50 nm/min, band width 2 nm, and 3 accumulations per sample.     (16) beta=105.779 (2) c=21.0556 (13)

S34
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Supplementary Figure 6. Structures of the stable and metastable (obtained after irradiation) isomers present in the X-ray crystal structure of Mn2. a Capped stick style view of the X-ray structure of the stable (R,P,Sa)-Mn2 isomer. b Capped stick style view of the X-ray structure of the metastable (R,M,Ra)-Mn2 isomer. Color coding: dark blue: phosphate ligand 1, red: salen ligand; magenta: ethylene bridge of salen. green: manganese center; hydrogen atoms have been omitted for clarity.
The crystal structures of (S,M,Ra)-Mn2 in Fig. 3a and (R,P,Sa)-Mn2 in the Supplementary Figure  6a were selected from the stable rac-Mn2 crystal. The crystal structures of (S,P,Sa)-Mn2 in  Reflections were measured on a Bruker D8 Quest diffractometer with sealed tube and Triumph monochromator (λ = 0.71073Å). The software package used for the intensity integration was Saint (v8.40a). Absorption correction was performed with SADABS. The structures were solved with direct methods using SHELXT-2014/5. Least-squares refinement was performed with SHELXL-2018/3 against | ℎ | 2 of all reflections. Non-hydrogen atoms were refined freely with anisotropic displacement parameters. Hydrogen atoms were placed on calculated positions or located in difference Fourier maps. All calculated hydrogen atoms were refined with a riding model.
(R,P,Sa)-Mn2 (metastable) single crystal preparation procedure: Irradiation of a solution of stable Rac-Mn2 (c = 1 mg/mL in CH2Cl2) for 30 minutes with λ = 365 nm light furnished a solution of metastable Rac-Mn2. Evaporation of the solvent followed by crystallization from toluene/n-heptane (1:8, v/v) furnished metastable Rac-Mn2 in the crystalline state. The crystal of metastable Rac-Mn2 was dark-brownish colored and had a needle shape. Unfortunately, due to the small size of the crystal, only a partial diffraction data set with low resolution could be obtained. With this limited dataset the non-hydrogen atoms could only be refined isotopically and no hydrogens could be placed via a difference map. The crystallographic information of the tentative metastable structure is given below in the form of a .res file.  The absolute configurations of the enantioenriched epoxides 17b-20b were assigned on the basis of the sign of the optical rotation as reported by Jacobsen et al. S5 Epoxides 17b-20b generated with catalysts (S,M,Ra)-Mn2 or (R,M,Ra)-Mn2 displayed positive optical rotations corresponding to the (1aR,7bR)-configuration. S5 Those produced by (R,P,Sa)-Mn2 or (S,P,Sa)-Mn2 displayed negative optical rotations corresponding to the (1aS,7bS)-configuration. S5 The correlation between the (Ra) axial chirality of the phosphate ligand and the (1aR,7bR) absolute configuration of the enantioenriched epoxide was also observed by List et al. S2,S6 For the styrene oxide series (epoxides 21b-23b), which displayed low enantioselectivities (e.e. < 25%), optical rotation measurements did not prove reproducible: while a first measurement of a sample could give a positive optical rotation, a second or third measurement could suddenly give a negative optical rotation. We attribute this inaccuracy to the low level of enantioenrichment for these compounds. Nonetheless, the absolute configurations of the styrene oxides were determined by comparing the HPLC elution orders to authentic samples (i.e. (R)-and (S)-phenyloxirane/styrene oxide 21b) that were obtained from commercial suppliers (See Supplementary Figure 82). The chiral HPLC elution order for the enantiomers of the related epoxides on the same chiral column is assumed to be the same, i.e. (R)-22b and (R)-23b are the first eluted enantiomers, and (S)-22b and (S)-23b are the second eluted enantiomers.
Finally, the absolute configurations of the enantioenriched epoxides 24b and 25b were determined by comparison of the HPLC traces of these epoxides produced by Mn2 to those produced by Jacobsen's catalyst (R,R)-Mn16. The latter catalyst has been reported to produce enantioenriched epoxides (1S,6S)-24b S7 and (1aR,6aS)-25b, S8 both of which were the second eluted enantiomers.

Mn2 obtained via different route and the corresponding catalytic results
Supplementary Table 8. Catalytic results of Mn2, obtained via different synthesis routes, and enantioselective effects (See also Supplementary Figure 9 and 10).  Supplementary Table 7 and those in red are presented in Supplementary Table 8.