A Thioxanthone Sensitizer with a Chiral Phosphoric Acid Binding Site: Properties and Applications in Visible Light‐Mediated Cycloadditions

Abstract

Ac hiral phosphoric acid with a2 ,2'-binaphthol core was prepared that displays two thioxanthone moieties at the 3,3'-position as light-harvesting antennas.D espite its relatively lowt riplet energy,t he phosphoric acid was found to be an efficient catalystf or the enantioselective intermolecular [2+ +2] photocycloaddition of b-carboxyl-substitutedc yclic enones (e.r.u pt o9 3:7). Binding of the carboxylic acid to the sensitizeri ss uggested by NMR studies and by DFT calculations to occurb ym eans of two hydrogen bonds. The binding event not only enables an enantioface differentiationb ut also modulates the triplet energy of the substrates.Recent interest in visible light-mediatedr eactions has triggered al arge number of studies towards the synthesis of new chromophores and chiral catalysts. [1] The long known thioxanthone chromophore [2] has been revisited in the context of triplet sensitization [3] and it has been attached to chiral scaffolds fora p-plications in enantioselective photochemistry. [4] The most frequently used chiral modification is represented by compound 1 (Figure 1) [4a] in which at hioxanthone is attached via an oxazole to positionC 7o f1 ,5,7-trimethyl-3-azabicyclo[3.3.1]nonan-2-one. The latter device serves as ah ydrogen bonding site [5] and allows to process lactamsi n[ 2 + +2] photocycloaddition [4a, 6] and deracemization [7] reactions. By attachment to a chiral bisoxazoline, thioxanthonec an be part of ab ifunctional chiral metal catalyst and ligand 2 has been successfully employedi nt he Ni-catalyzed oxygenation of b-ketoesters. [4b] Chiral imidazolinone-based organocatalysts have recently been reported for enamine catalysis in which the thioxanthone acts via singlee lectront ransfer. [4d] However,n ot any binding motif known from thermalr eactions will automatically lead to as uccessfulc hiral catalyst. Thiourea-linked thioxanthones such as 3, for example, did not display the expected enantioselectivity in photochemical reactions. [4c] Nonetheless, given the limited number of substrates that can yet be processed by chiral thioxanthones, it seems desirable to further investigate possible binding motifs to which a thioxanthone entity can be attached. In this communication, we describe the synthesis of a C 2 -symmetric chiral phosphoric acid with two thioxanthone units and report on preliminary studies as to its mode of action in photochemical [2+ +2] cycloaddition reactions.Since their initial use in organocatalysis, [8] chiral phosphoric acids have emerged as ah ighly efficient class of compounds for ap lethora of applications. [9] Most phosphoric acids display aryl groups in positionsC 3a nd C3' of the 2,2'-binaphthol core and we envisaged that these positions would serve as suitable pointso fattachment for at hioxanthone unit. However,t he direct linkage of a9 -oxo-9H-thioxanthen-3-yl group to posi-Figure 1. Structure of chiral thioxanthones 1-3 with as ubstrate or metal binding site (in gray).

Preparation of Chiral Photosensitive Organocatalysts and Their Application for the Enantioselective Synthesis of 1,2-Diamines

“…Worthy of note, during the course of this study, Bach and co-workers reported other C2-symmetric chiral photensitizers derived from chiral phosphoric acids which he applied to enantioselective [2+2] photo-cycloadditions. 12 Scheme 1. Enantioselective catalytic photochemical reactions.…”

Visible Light-Mediated Photochemical Reactions of 2-(2′-Alkenyloxy)cycloalk-2-enones

“…While visible light-mediated, sensitized reactions of styrenes and related compounds have recently received broad attention, 7 studies with cyclic enones have remained scarce. 8 (b) It was expected that other reaction pathways might be feasible depending on the structure of the chromophore and the substitution pattern of the olefin. Most importantly, [2 + 2] photodimerization and hydrogen abstraction 9 were foreseen as competing reactions which would in turn lead to intriguing new structures.…”

Recent Visible Light and Metal Free Strategies in [2+2] and [4+2] Photocycloadditions

“…Recently, Bach and co-workers introduced an unprecedented chiral phosphoric acid XVII including two thioxantone moieties at the 3,3' position of the 2,2'-binaphthol core as new photosensitizer for cycloaddition reactions. [29] Actually, this new phosphoric acid XVII showed to efficiently catalyze the asymmetric intermolecular [2 + 2] photocycloaddition of βcarboxyl-substituted cyclic enones 19 leading to the corresponding products 21 with good enantioselectivity (Scheme 14a). As suggested by DFT calculations and NMR studies, the binding between the carboxylic acid and the photocatalyst (Scheme 14b), which occur through the establishment of two hydrogen-bonding points, should induce a proper enantioface differentiation and, at the same time, lower the triplet energy of the substrate in order to enable the energy transfer mechanism.…”

“…Recently, Bach and co‐workers introduced an unprecedented chiral phosphoric acid XVII including two thioxantone moieties at the 3,3’ position of the 2,2’‐binaphthol core as new photosensitizer for cycloaddition reactions [29] . Actually, this new phosphoric acid XVII showed to efficiently catalyze the asymmetric intermolecular [2+2] photocycloaddition of β‐carboxyl‐substituted cyclic enones 19 leading to the corresponding products 21 with good enantioselectivity (Scheme 14a).…”