Force-Triggered Atropisomerization of a Parallel Diarylethene to Its Antiparallel Diastereomers

This paper describes a mechanical approach to inducing the atropisomerization of a parallel diarylethene into its antiparallel diastereomers exhibiting distinct chemical reactivity. A congested parallel diarylethene mechanophore in the (Ra,Sa)-configuration with mirror symmetry is atropisomerized to its antiparallel diastereomers with C2 symmetry under ultrasound-induced force field. The resulting stereochemistry-converted material gains symmetry-allowed reactivity toward conrotatory photocyclization.


General Considerations
All reactions were conducted under standard air-free conditions under an atmosphere of nitrogen gas with magnetic stirring unless otherwise mentioned. All reactants and solvents were purchased from commercial suppliers and used without further purification unless otherwise noted. Flash chromatography was performed on a Biotage Isolera System with Yamazen Corp. universal silica gel columns (Pore Size 60 angstroms, Particle Size 40-63 microns).
NMR spectra were acquired on a Bruker Avance III HD 400 MHz spectrometer. 1 H NMR spectra are reported relative to residual protonated solvent (7.26 ppm for CHCl3). 13 C NMR spectra are reported relative to solvent signals (77.16 ppm for CHCl3). Multiplicity abbreviations are as follows: s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, ABq = AB quartet, m = multiplet, br = broad.
Mass spectra were acquired on a DART-SVP (Direct Analysis in Real Time) ion source (IonSense, Saugus, MA) coupled to an Exactive Orbitrap mass spectrometer (Thermo Scientific, Bremen, Germany) at the Cornell Chemistry Mass Spectrometry Facility.

Molecular weight distributions of polymers were measured at the Michael Szwarc Polymer
Research Institute at SUNY College of Environmental Science and Forestry, using Waters sizeexclusion chromatography line (SEC) in THF at a flow rate of 0.8 mL/min. Fourteen poly(styrene) standards (Polymer Standards Service) were used for calibration.
All solution optical spectra were acquired of samples in quartz cuvettes. Electronic absorbance spectra were acquired with an Evolution 201 UV-visible spectrophotometer in double-beam mode using a solvent-containing cuvette for background subtraction spectra of solution samples. Fluorescence spectra were measured with an Agilent Cary Eclipse G9800A Fluorescence Spectrophotometer ( Figure S8) or a Horiba Scientific FluoroMax Spectrofluorometer ( Figure S9).
Ultrasound experiments were performed using a Vibra Cell 505 liquid processor equipped with a 13 mm full wave solid probe (254 mm long, Sonics, part #630-0217), sonochemical adapter (Sonics, part #830-00014), and a 10-50 mL reaction vessel (Sonics, part #830-00012). All sample solutions were purged with argon for 20 minutes prior to ultrasonication. Argon gas bubbling is continued through ultrasonication experiments. The reaction vessel was immersed in an ice bath during the ultrasonication. The ultrasound treatments were performed in pulse mode (1s on/2s off) with 20% amplitude. All reported sonication times are "sonication-on" time.
UV irradiations at 365 nm or 254 nm were conducted using a hand-held UV lamp (Chemglass, part # CLS-1625). The lamp wattage is 6 watts. Visible light irradiations were performed using an iPhone flashlight.

DFT Calculations
Density Functional Theory (DFT) calculations using the constrained geometries simulate external force (CoGEF) technique were performed on Spartan '20 at B3LYP/6-31G* level of theory (J. Chem. Phys. 2000, 112, 7307-7312;J. Am. Chem. Soc. 2020, 142, 16364-16381). A truncated DAEs structure was first equilibrated. Starting from this local energy minimum (relative energy = 0 kJ/mol), the distance between the two terminal methyl groups was increased in small incremental steps (0.05 Å per step), and the energy of the molecule was minimized at each step. The force at each elongation step was calculated from the slope of the energy-strain curve. Figure  S1 shows the DFT calculation for the 5-substituted DAE which is the focus of this study. Although DFT results predict that the 4-, 6-, and 7-substituted regioisomers are also active, we will report DFT and experimental results in a separate study. The unusually low maximum force suggests the atropisomeric DAE mechanophore is highly mechanosensitive. The mechanosensitivity of this type of stereochemistry-converting mechanophores is supported by preliminary experimental results ( Figure S9 and Figure S10) and will be systematically investigated in follow-up studies. Figure S1a. The structure of the truncated 5-substituted DAE at equilibrium geometry (left), immediately prior to the stereochemistry conversion (middle), and immediately after the mechanical conversion (right). The maximum force 0.6 nN was calculated from the slope of the curve.
The rotational barrier under thermal conditions was computed using DFT calculations at the B3LYP/6-31G* level of theory. The dihedral angle between the ethene bridge and a benzothiophene was increased in small incremental steps (1˚ per step), and the energy of the molecule was minimized at each step.

Determination of Photostationary State
The ring-closed DAE (±)-1C2 closed was synthesized, isolated, and structurally characterized (see the Synthetic Details). A dilute solution of the ring-closed DAE in acetonitrile was prepared in the dark, and its optical density value ODclosed at 519 nm was measured by UV-vis spectroscopy to be 0.1024. This colored solution was irradiated with a white flashlight for 5 min, triggering the ring-opening reaction and the complete discoloration of the solution. The resultant solution was then irradiated under a hand-held UV lamp at 365 nm for 2 min to achieve its photostationary state (PSS). The UV-vis absorption spectrum of the PSS solution was measured, and its optical density value ODPSS at 519 nm was determined to be 0.0874. The percentage conversion in the PSS was calculated: DAEclosed% = ODPSS/ODclosed = 85%.       . Benzothiadiazole (0.50 g, 2.6 mmol) was suspended in 48% w/w aq. HBr (10 mL) in a 20 mL pressure reaction vessel equipped with a stir bar. Under dark conditions, bromine (0.5 mL, 9.7 mmol) was added, and the mixture was stirred at 120 °C. After two days, the reaction was cooled to room temperature, and another 0.5 mL of bromine was added. The sealed reaction was continued at 120 °C in the dark for another two days. The reaction was cooled down to room temperature followed by the addition of ice to form yellow solid precipitates, which were collected by filtration, washed with water, and washed multiple times with methanol to remove water. The resultant crude is a mixture of the monobromination and dibromination products which was carefully washed with small portions of dichloromethane (~2 mL each wash) multiple times to remove the readily soluble monobromination product, affording the desirable dibromination product BBT as a light-yellow solid (242 mg, 27% thiophene-5-carboxaldehyde (S1). A round bottom flask equipped with a stir bar was charged with 5-bromo-2-methyl-1-benzothiophene (2.54 g, 11.19 mmol) and 40 mL anhydrous THF. The solution was cooled to −78 °C in an acetone/dry ice bath, and n-butyllithium (2.5 M in hexanes, 6.70 mL, 16.77 mmol) was added dropwise. After stirring the mixture for 30 min at −78 °C, DMF (2.59 mL, 33.55 mmol) was added to the mixture dropwise. The mixture was then allowed to warm up to room temperature for over 30 min, followed by the slow addition of 10% NH4Cl (100 mL) to quench the reaction. The mixture was extracted with EtOAc (100 mL), and washed with brine (100 mL). The organic fraction was dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a crude mixture. The crude product was used in the next step without further purification. Crude 1 H NMR (400 MHz, CDCl3): 10.07 (s, 1H), 8.14 (d, J = 1.6 Hz, 1H), 7.87 (d, J = 8.3 Hz, 1H), 7.77 (dd, J = 8.3, 1.6 Hz, 1H), 7.11 (s, 1H), 2.63 (d, J = 1.2 Hz, 3H).

General Polymerization Procedures
A 10 mL Schlenk flask equipped with a stir bar was charged with the initiator (1 equiv), methyl acrylate (~1,200 equiv), Me6TREN (2 equiv), and DMSO (equal volume to methyl acrylate). The solution was deoxygenated via three freeze-pump-thaw cycles, and then backfilled with nitrogen. The flask was opened briefly and freshly cut copper wire (1.0 cm length, 20 gauge) was added to the frozen mixture under a blanket of nitrogen. Then, the solution was deoxygenated again under vacuum and backfilled with nitrogen. After stirring at room temperature for 35 min, the flask was opened to air and the solution was diluted with DCM. The polymer solution was precipitated into cold methanol (3x) and the isolated polymer was dried thoroughly under vacuum. Figure S11. GPC traces and molecular weight data for some polymers reported in this paper.

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Crystal data and structure refinement for Rxh1 (7