Enantioselective Intramolecular [2 + 2]-Photocycloaddition Reactions of 4-Substituted Quinolones Catalyzed by a Chiral Sensitizer with a Hydrogen-Bonding Motif

Abstract

Six 2-quinolones, which bear a terminal alkene linked by a three- or four-membered tether to carbon atom C4 of the quinolone, were synthesized and subjected to an intramolecular [2 + 2]-photocycloaddition. The reaction delivered the respective products in high yields (78-99%) and with good regioselectivity in favor of the straight isomer. If conducted in the presence of a chiral hydrogen-bonding template (2.5 equiv) at low temperature in toluene as the solvent, the reaction proceeded enantioselectively (83-94% ee). An organocatalytic reaction was achieved when employing a chiral hydrogen-bonding template with an attached sensitizing unit (benzophenone or xanthone). The xanthone-based organocatalyst proved to be superior as compared to the respective benzophenone. Closer inspection revealed that the reaction of 4-(pent-4-enyloxy)quinolone leading to a six-membered ring, annelated to the cyclobutane, was less enantioselective (up to 41% ee with 30 mol % catalyst) than the reaction of 4-(but-3-enyloxy)quinolone leading to a five-membered ring (90% ee with 5 mol % and 94% ee with 20 mol % catalyst). Photophysical data (emission spectra, laser flash photolysis experiments) proved that the latter photocycloaddition was significantly faster, supporting the idea that the dissociation of the substrate from the catalyst prior to the photocycloaddition is responsible for the decreased enantioselectivity. Under optimized conditions, employing 10 mol % of the xanthone-based organocatalyst at -25 °C in trifluorotoluene as the solvent, three of the other four substrates gave the intramolecular [2 + 2]-photocycloaddition products with high enantioselectivities (72-87% ee). In all catalyzed reactions, the yields based on conversion were moderate to good (40-93%).

A Dual-Catalysis Approach to Enantioselective [2 + 2] Photocycloadditions Using Visible Light

“…Bach, whose laboratory has reported the only highly enantioselective catalytic photocycloadditions to date, has approached this problem by designing elegant reactions where the catalyst-substrate complex absorbs light at longer wavelengths than the free substrate. This has been accomplished either by using a chiral hydrogen-bonding xanthone-based photosensitizer (13–15) or by using a chiral Lewis acid catalyst capable of inducing a bathochromic shift in the bound substrate (16, 17). In both cases, Bach has been able to achieve impressive enantioselectivities with substoichiometric chiral controllers.…”

Chirality effects in gas-phase spectroscopy and photophysics of molecular and ionic complexes: contribution of low and room temperature studies

“…The role of chirality in photo-induced processes has been well documented in solution [254][255][256][257][258][259]. Most of the observed selectivity rests on enantiodifferentiation in the ground state, through enantioselective contact pair formation, or through hydrogen bonding of the photochemically produced intermediate with an optically active agent [257,258,260].…”

“…Most of the observed selectivity rests on enantiodifferentiation in the ground state, through enantioselective contact pair formation, or through hydrogen bonding of the photochemically produced intermediate with an optically active agent [257,258,260]. In some cases, enantioselectivity is explained in terms of formation of exciplex or triplex involving enantioselective interactions [261,262].…”

Mechanism of the Enantioselective Intramolecular [2 + 2] Photocycloaddition Reaction of Coumarin Catalyzed by a Chiral Lewis Acid: Comparison with Enone Substrates

“…[17][18][19] In contrast to the two-step approach, the notable strategy is to employ noncovalent interactions between the catalyst and its substrate to provide a chiral environment. By using several entities of this type including cyclodextrins [20][21][22][23] and hydrogen-bonding templates, [24][25][26][27][28][29] the direct approach shows an excellent performance in both enantioselectivity and yield, and has the advantage that it is not necessary to first add and then remove the auxiliary. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 As a promising solution，the Lewis acid catalysts have been considered as the potential chiral templates to carry out enantioselective photochemical reactions.…”