Geometric E→Z Isomerisation of Alkenyl Silanes by Selective Energy Transfer Catalysis: Stereodivergent Synthesis of Triarylethylenes via a Formal anti‐Metallometallation

Abstract An efficient geometrical E→Z isomerisation of alkenyl silanes is disclosed via selective energy transfer using an inexpensive organic sensitiser. Characterised by operational simplicity, short reaction times (2 h), and broad substrate tolerance, the reaction displays high selectivity for trisubstituted systems (Z/E up to 95:5). In contrast to thermal activation, directionality results from deconjugation of the π‐system in the Z‐isomer due to A1,3‐strain thereby inhibiting re‐activation. The structural importance of the β‐substituent logically prompted an investigation of mixed bis‐nucleophiles (Si, Sn, B). These versatile linchpins also undergo facile isomerisation, thereby enabling a formal anti‐metallometallation. Mechanistic interrogation, supported by a theoretical investigation, is disclosed together with application of the products to the stereospecific synthesis of biologically relevant target structures.

The reaction was stirred at room temperature overnight, quenched with ice-cooled H2SO4 (5%, aq.) at 0°C and filtered over a celite plug. The organic phase was separated, the aqueous phase was extracted with Et2O (3x 10 mL), the combined organic phases were dried over MgSO4 and the crude product concentrated in vacuo.
Purification by column chromatography (SiO2, 100% CH) yielded E-11 as a colorless oil (556 mg, 59%); analytical data in agreement with the literature. [7] 2H; H8), 7 1.1 eq.) was added slowly and the mixture was stirred for 30 min before trimethylchlorosilane (0.18 mL, 1.45 mmol, 1.2 eq.) was added. The reaction was stirred overnight while being allowed to gradually warm to rt. The reaction was quenched by the addition of water, the organic phase was separated, the aqueous phase was extracted with Et2O (3x), dried over MgSO4 and concentrated in vacuo.
Purification by column chromatography (SiO2, 100% CH) yielded Z-13 as a colorless oil (54 mg, 18%). 31.25 mL, 50 mmol, 1.0 eq.) was added at 0°C and the mixture was stirred for 1 h at 0°C before propiophenone (6.65 mL, 50 mmol, 1.0 eq.) was added and then stirred for 16 h while being allowed to warm up to room temperature. The reaction was quenched by the addition of water (50 mL), the organic phase was separated and the aqueous phase was extracted with Et2O (3x 50 mL). The combined organic phases were dried over MgSO4, concentrated in vacuo and the crude product was purified by column chromatography (SiO2, CH) to yield 34 as a colorless oil (5.03 g, 76%); analytical data in agreement with the literature. [ ppm.

(E)-Dimethyl(2-phenylbut-1-en-1-yl)silanol (E-20)
A Schlenk tube was charged with magneisum turnings (304 mg, 12.5 mmol, 2.5 eq.) and flame-dried before dry THF (15 mL) was added under argon atmosphere. The tube was placed into the sonication bath for 15 min. After addition of a grain of iodine, 1 mL of a solution of vinyl bromide 35 (1055 mg, 5 mmol, 1.0 eq.) in dry THF (5 mL) was added dropwise, the mixture was put into the sonication bath for another 10 min and then refluxed until the Grignard-reaction was initiated. The rest of the vinyl bromide solution was added slowly over 15 min, followed by chlorodimethylsilane (0.72 mL, 6.50 mmol, 1.3 eq.), and the mixture was refluxed for overnight. The reaction was allowed to come to room temperature before 1 M HCl (10 mL) was added at 0°C. The organic phase was separated and the aqueous phase was extracted with cyclohexane (3x10 mL (Z)-Trimethyl(2-phenyl-2-(tributylstannyl)vinyl)silane (Z-22) [9] Prepared according to General Procedure D, phenylacetylene (0.55 mL, 5.0 mmol, 1.0 eq.) was converted to Z-22 in 1 h yielding a colourless oil (2209 mg, 95%) after purification by column chromatography (100% n-pentane). Analytical data in agreement with the literature. [  Benzyldimethylethynylsilane (36) [6] To an oven-dried two-neck flask equipped with a reflux condenser was added benzyldimethylchlorosilane (2 mL, 10.8 mmol, 1 eq.) and dry THF (5 mL) under a dry argon atmosphere. Ethynylmagnesium bromide (21.5 mL of 0.5 M solution in THF, 10.8 mmol, 1.0 eq.) was added via syringe and the solution was heated to reflux with stirring for 3 h. After the reaction was complete, solvent was removed under reduced pressure and the crude residue was purified by short path distillation to afford the desired product as a colorless oil (1.3 g, 69%). Analytical data was in agreement with the literature. [6] (

Photosensitised isomerisation of vinyl silanes General Procedure E for the isomerisation of vinyl silanes
A round-bottom flask was charged with the specific vinyl silane (0.1 mmol, 1.0 eq.) and benzophenone (0.005 mmol, 0.05 eq.) in degassed cyclohexane (1.5 mL). The reaction vessel was sealed with a septum, equipped with an argon balloon and placed above the UV-lamp with a distance of approximately 0.5 cm. The mixture was stirred for 2 h at room temperature under UV light irradiation (UVA LED, 365 nm). The crude reaction mixture was filtered through a plug of SiO2, diluted with cyclohexane (5 mL) and concentrated in vacuo. The E-/Z-isomer ratio was determined by the integration of the 1 H NMR spectra.

Subsequent transformations of vinyl silanes
General Procedure F for Hiyama-Denmark cross coupling reactions of Z-15 [16] A flame-dried Schlenk-tube was charged with Z-15 (0.12 mmol, 1.2 eq.) and dry THF (0.8 mL) under argon atmosphere. Tetrabutylammoniumfluoride trihydrate (3.0 eq.) was added portionwise and the mixture was stirred for 10 min at room temperature.
The specific halide (1.0 eq.) and Pd(dba)2 (0.05-0.75 eq.) were added and the mixture stirred at room temperature for 24 h. The crude reaction mixture was filtered through a plug of silica, diluted with EtOAc, concentrated in vacuo and purified by column chromatography (SiO2, specified combination of solvents).  [17] An oven-dried Schlenk-flask was charged with Z-14 (
The reaction was stirred at room temperature for 16 h. The reaction mixture was diluted with DCM (20 mL) and quenched with aq. sat.

DFT CALCULATIONS Method
All structures were optimised without geometry constraints using the TPSS functional [21] and an atom-pairwise dispersion correction (D3) [22] . A flexible triple zeta basis set (def2-TZVP) [23] was used in all calculations. For the calculation of the free enthalpy contributions (G RRHO (298K)), a rotor approximation was applied for vibrational modes with wave numbers below 100 cm -1 . [24] The nature of all optimised stationary points was proven by the presence of either 0 (minimum) or 1 (transition structure) imaginary vibrational frequency.

Figure S5
Structures of (E)/(Z) isomers and triplet ground state of 2. In square brackets: relative free energies (ΔG(298)) in kcal/mol. In curly brackets: vertical (single point) energy of the triplet state.

Figure S6
Structures of (E)/(Z) isomers and triplet ground state of 1. In square brackets: relative free energies (ΔG(298)) in kcal/mol. In curly brackets: vertical (single point) energy of the triplet state.

Orbital analysis of the triplet excitation of (E)-and (Z)-1
In both ground (S0) states of (E)-1 and (Z)-1, HOMO and LUMO (MOs 55 and 56) are constituted mainly by the π/π* orbitals of the ethene bond, with significant admixture of phenyl π orbitals.
The (forbidden) first triplet excitation to T1 of (E)-1 corresponds to a HOMO-LUMO excitation.
The two singly occupied orbitals of T1 (MOs 55a and 56a) are both delocalised over the styryl system and lead in total to a localisation of spin density in the vinyl group, allowing the triplet state to attain the energy minimum by rotation around the vinyl C-C bond.
The more distorted styryl moeity of (Z)-1, however, shows a significantly higher energy of the forbidden first vertical triplet excitation (87 kcal/mol) in the TDDFT (B-LYP) calculation and of the energy of the (relaxed) T1 wave function (100 kcal/mol with PWPB95-D3) at the same geometry. The larger torsional angle (61.6°) aggravates the mixing of ethene and phenyl π orbitals and leads to two rather localised α spin orbitals in the T1 state (MOs 55a and 56a in Figure S6). Spin density is accumulated mainly in the phenyl ring, suggesting a lower tendency to rotate the vinyl C-C bond. Of course, thermal motion would allow the molecule to leave the S0 minimum geometry and change the spin density distribution in the further course.