Enantioselective Lewis Acid Catalysis in Intramolecular [2 + 2] Photocycloaddition Reactions: A Mechanistic Comparison between Representative Coumarin and Enone Substrates

Abstract

The intramolecular [2 + 2] photocycloaddition of three 4-(alk-4-enyl)coumarins and three 1-(alk-4-enoyl)-2,3-dihydropyridones was studied in the absence and in the presence of Lewis acids (irradiation wavelength λ = 366 nm). Spectral and kinetic data were collected for the respective parent compounds with a pent-4-enyl and a pent-4-enoyl chain. For the substrates with a methyl group in cis- or trans-position of the terminal alkene carbon atom (hex-4-enyl and hex-4-enoyl substitution), the stereochemical outcome of the [2 + 2] photocycloaddition was investigated. The mechanistic course of the uncatalyzed coumarin reactions was found to be a singlet pathway, whereas Lewis acid-catalyzed reactions proceeded with higher reaction rates in the triplet manifold. Contrary to that, the dihydropyridones underwent a fast triplet reaction in the absence of the Lewis acid. In the presence of a chiral Lewis acid the reactions slowed down but, due to the high extinction coefficient of the Lewis acid/dihydropyridone complexes at λ = 366 nm, still resulted in high enantioselectivity.

Chromophore Activation of α,β‐Unsaturated Carbonyl Compounds and Its Application to Enantioselective Photochemical Reactions

“…Whereas the enantioface differentiation by the Lewis acid occurs in analogy to that with the coumarins, the reaction mechanisms differ significantly. In the presence of a Lewis acid, a rate enhancement was observed for the coumarins, whereas the reactions of enones were retarded 22. The quantum yields are consistent with these observations.…”

“…The cycloaddition did not occur stereospecifically, and in a later study, it was shown that the aforementioned reasons for the catalytic effect of a Lewis acid also applied to this reaction 22. The quantum yield Φ of the reaction 10 a → 11 a amounts to 2×10 −3 without a Lewis acid, whereas Φ =0.09 in the presence of chiral Lewis acid 12 .…”

Brønsted Acid Catalysis in Visible‐Light‐Induced [2+2] Photocycloaddition Reactions of Enone Dithianes

“…This observation is in agreement with earlier studies that reported on a similar behavior for coumarins and other α,β‐unsaturated β‐aryl‐substituted carbonyl compounds 6. The reason for the intensity increase is a bathochromic shift of the strong short‐wavelength ππ* absorption 5c. As a consequence of the high absorption cross‐sections of such Lewis acid/enone complexes, [2+2] photocycloaddition reactions can be rendered enantioselective in the presence of a chiral Lewis acid 5, 7, 8…”

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

“…30,31 Following the previous works regarding the thermal cycloaddition reactions catalyzed by a chiral Lewis acid, [32][33][34][35] Bach and his coworkers applied chiral oxazaborolidine-AlBr 3 based Lewis acid catalyst (1 see scheme 1) to enable the enantioselective intramolecular [2+2] PCA of coumarin (2) and a typical enone substrate, i.e., 5,6-dihydro-4-pyridones (3). [36][37][38][39] As shown in scheme 1, the stereochemical PCA products 4 and 5 have been obtained with the satisfied yield (~0.84) and high enantioselectivity (82~90% ee) in the presence of catalyst 1 when the unselective background reaction was noticeably suppressed at high catalyst loadings (typically ~50 mol %). However, the mechanistic courses of coumarins were found to be totally different from the PCA reaction of dihydropyridones.…”

“…36,39 In comparison with the uncatalyzed background reactions, the reaction rates were accelerated for the cycloaddition reaction of coumarins but slowed down in the presence of a chiral Lewis acid of dihydropyridones. 36,39 All these experimental observations indicate that it is a challenging issue to understand the regulatory mechanism mediated by the chiral Lewis acid and to effectively suppress the unselective background reaction. To achieve a general strategy for controlling racemic background reactions, an innovative approach was developed in Yoon's group 7,40-46 by the introduction of one more transition 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 metal complex that is able to trigger the photoredox reaction regulated by single-electron transfer.…”