A complementary pair of enantioselective switchable organocatalysts† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02462b Click here for additional data file.

A pair of enantioselective switchable bifunctional catalysts are shown to promote a range of conjugate addition reactions in up to 95 : 5 e.r. and 95% conversion.

Upon completion, the crude was purified by TLC, and the chirality of the product ascertained by HPLC (chiralpak IC, 90:10 Hexane:iPrOH, major enantiomer produced by catalyst 1 t r = 18.4 min, for catalyst 2 t r = 29.9 min).

Optimisation of light switching conditions for catalyst 1
The degree of isomerisation was monitored by following the integral ratio of the E and Z states of hydrazone proton H(55) (at c. 12 ppm and c. 16 ppm, see characterisation for full numbering).
A brief initial screen of light sources showed a 395 nm source to be the most efficient in promoting hydrazone isomerization. Initially problems with decomposition, particularly hydrazone hydrolysis, were observed. This could be prevented by the addition of molecular sieves, which also improved the E:Z ratio achieved. A significant improvement in final switching ratio was achieved by the addition of EtOAc to the solvent mixture (pure EtOAc could not be used due to insufficient solubility). Increasing the concentration of solution was deleterious to conversion. The timescale of switching could be accelerated to 20 min of irradiation by increasing the power and using CH 2 Cl 2 :EtOAc as solvent. This switching system also alleviated the previously observed decomposition, obviating the need for molecular sieves.

Optimisation of thermal switching of catalyst 1
The degree of isomerisation was monitored by following the integral ratio of the E and Z states of hydrazone proton H(55) (at c. 12 ppm and c. 16 ppm, see characterisation for full numbering).
Initial isomerization of catalyst 1 focused on pure thermal switching. More polar solvents were found to promote isomerization, and pleasing ratios could be obtained in DMF at 90 °C. However, the extended reaction time and high temperature required prompted us to search for effective acid catalysed switching conditions. The addition of TFA to EtOAc allowed virtually quantitative switching after one hour.

Procedure for switching of catalyst state during the course of reaction
Malonitrile (1.0 mg, 0.015 mmol), (E)-1-(furan-2-yl)-3-phenylprop-2-en-1-one (9 mg, 0.045 mmol) and catalyst 2 (0.75 mg, 0.75 μmol) were dissolved in CDCl 3 (0.7 ml). Conversion was measured periodically by 1 H NMR spectroscopy and comparison with authentic spectra of starting materials and product. After a given time, the reaction was diluted with 10 ml Et 2 O. The precipitate was collected via syringe filtration, and dissolved in CH 2 Cl 2 . The filtrate was stored at − 20 °C for the duration of the switching procedure. The relevant heat or light switch was performed on the catalyst, followed by aqueous extraction with saturated Na 2 CO 3 (aq) . After drying, the catalyst was recombined with the diluted reaction mixture. Solvent was removed in vacuo whilst the flask was cooled to 0 °C. The reaction mixture was immediately dissolved in CDCl 3 (0.7 ml) and monitored by NMR. This process was repeated using the alternate switching conditions after a suitable time had passed. No erosion of stereochemistry in the product was observed, as compared to the continuous reaction. Figure S1. Relative reactivity of ON and OFF states of catalyst 2 towards the addition of malonitrile to chalcone 22 by starting with the OFF state (left) or ON state (right, solid lines are a guide to the eye). A full switching cycle could be carried out during this reaction, starting from either 'ON' or 'OFF' catalyst, using 3.5 mol% of 2 (initial E:Z ratio 99:1 (ON) or 2:98 (OFF)). After 6 h the E-to-Z, or vice versa, stimulus was applied (0.1% CF 3 CO 2 H, 60 min, 50 °C or 395 nm, 700 mW, 20 min) and the reaction continued. After 24 h (for initially OFF 2) or 21 h (for initially ON 2) the opposing stimulus was applied reverting catalyst 2 to its initial state.