Bifunctional Molecular Photoswitches Based on Overcrowded Alkenes for Dynamic Control of Catalytic Activity in Michael Addition Reactions

Abstract

The emerging field of artificial photoswitchable catalysis has recently shown striking examples of functional light-responsive systems allowing for dynamic control of activity and selectivity in organocatalysis and metal-catalysed transformations. While our group has already disclosed systems featuring first generation molecular motors as the switchable central core, a design based on second generation molecular motors is lacking. Here, the syntheses of two bifunctionalised molecular switches based on a photoresponsive tetrasubstituted alkene core are reported. They feature a thiourea substituent as hydrogen-donor moiety in the upper half and a basic dimethylamine group in the lower half. This combination of functional groups offers the possibility for application of these molecules in photoswitchable catalytic processes. The light-responsive central cores were synthesized by a Barton-Kellogg coupling of the prefunctionalized upper and lower halves. Derivatization using Buchwald-Hartwig amination and subsequent introduction of the thiourea substituent afforded the target compounds. Control of catalytic activity in the Michael addition reaction between (E)-3-bromo-β-nitrostyrene and 2,4-pentanedione is achieved upon irradiation of stable-(E) and stable-(Z) isomers of the bifunctional catalyst 1. Both isomers display a decrease in catalytic activity upon irradiation to the metastable state, providing systems with the potential to be applied as ON/OFF catalytic photoswitches.

Rational design of allosteric switchable catalysts

“…[ 76 ] Recently, they developed the second‐generation molecular motor to construct a new artificial stimulus‐response chiral catalytic system. [ 77 ] Unlike the first‐generation molecular motor, the second‐generation molecular motor has different metastable states during the rotation process. They introduced the biphenyldiol unit into the molecular switch and found that the chiral center could induce the helical chirality of the molecular switch.…”

Photoswitchable catalysis based on the isomerisation of double bonds

“…Bifunctional molecular photoswitches based on the overcrowded alkene scaffold found in the so-called second generation molecular motors 41 have been recently investigated as light-responsive catalysts. 42 Photoresponsive thioureas 27 were synthesised in both E and Z forms, which showed efficient photoisomerisation upon irradiation with 312 nm light (Scheme 13). However, the photogenerated metastable states (M)-Z-27 and (M)-E-27 did not show reversible photoisomerisation upon irradiation with 365 nm light as happens in the unfunctionalised counterparts.…”

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…The cooperation of thiourea and tertiary amine in cis states was found a key factor for stereoselectivity of Henry reaction of nitromethane and fluorinated ketones and Michael reaction of bromonitrostyrene and pentanedione. Bisfunctional, photoswitchable, dual stereoselective catalysts based on the idea of unidirectional molecular motors were designed by Feringa and co-workers (Figure 28) [330,331]. The cooperation of thiourea and tertiary amine in cis states was found a key factor for stereoselectivity of Henry reaction of nitromethane and fluorinated ketones and Michael reaction of bromonitrostyrene and pentanedione.…”