Intermolecular asymmetric dearomative photocycloaddition of (benzo)furans with excited alkenes via cage-confined catalysis

doi:10.1016/S1872-2067(26)65001-2

Abstract

Abstract:

Photocycloaddition has recently emerged as a powerful dearomatization method; however, there is a challenge in the reaction between excited alkenes and non-photoactive aromatics, particularly for intermolecular cycloaddition. Moreover, advancements in asymmetric dearomative photocycloaddition have remained stagnant. In this study, we present an efficient approach to achieve intermolecular asymmetric dearomative photocycloaddition between excited cinnamates and non-photoactive (benzo)furans by virtue of cage-confined photocatalysis. The nanoconfined chemical spaces in cage-pockets facilitate heteromolecular co-encapsulation of substrates carrying variable functional groups, promoting efficient asymmetric dearomatization in high levels of chemo-, diastereo-, and enantioselectivity for the synthesis of three-dimensional chiral cyclic molecules.

Key words: Asymmetric photocatalysis, Asymmetric dearomatization, [2+2] Photocycloaddition, Biomimic catalysis, Metal-organic cage

Jia Ruan, Wenjing Chen, Ziqian Li, Peng Hu, Cheng-Yong Su. Intermolecular asymmetric dearomative photocycloaddition of (benzo)furans with excited alkenes via cage-confined catalysis[J]. Chinese Journal of Catalysis, 2026, 85: 346-355.

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URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(26)65001-2

https://www.cjcatal.com/EN/Y2026/V85/I6/346

Figures/Tables 6

Fig. 1. Strategies for dearomative photocycloadition. (a) Previous strategies of dearomative photocycloaddition for different types of aromatics and alkenes. (b) Representative works for ADAPCs in catalytic fashion. (c) Intermolecular ADAPC with photoactive alkenes by cage-confined chiral-pockets of the artificial enzymatic photoreactor Λ-MOC-16 (Δ-MOC-16 produces opposite enantiomer).

Fig. 2. Initial studies. (a) 1a (0.2 mmol), 1b (0.1 mmol), 0.5 mol% Λ-MOC-16 and DMSO:H2O (1:3, 3 mL) were stirred under N2 for 24 h with white LEDs as the light source. (b) Stern-Volmer quenching plot of Λ-MOC-16 with 1a or 1b in DMSO: H2O (1: 3). Quenching rate Ksv(1a) = 1370 L/mol, Ksv(1b) = 186 L/mol. (c) UV-vis spectra of 1a (1 × 10-4 mol/L), 1b (1 × 10-4 mol/L), MOC-16 (1 × 10-5 mol/L) in mixed solvent (DMSO:H2O = 1:3, v:v), and normalized emission spectrum of white LEDs.

Table 1 Optimization study.

Entry	Solvent	Conversion of 1a^a (%)	Conversion of 1b^a(%)	Yield of 1 (d.r.)^a (%)	ee of 1^b (%)
1	DMSO:H₂O = 1:3, 3 mL	92	78	45 (10.5:1)	90
2	DMF:H₂O = 1:3, 3 mL	76	90	73 (4.7:1)	87
3	MeOH H₂O = 1:3, 3 mL	98	89	69 (5.5:1)	84
4	THF:H₂O = 1:3, 3 mL	88	58	42 (3.6:1)	76
5	Acetone:H₂O = 1:3, 3 mL	98	86	72 (5.2:1)	86
6	NMP:H₂O = 1:3, 3 mL	76	87	66 (4.9:1)	83
7	MeCN:H₂O = 1:3, 3 mL	>99	84	71 (6.2:1)	84
8	H₂O, 3 mL	71	52	37 (3.9:1)	88
9	DMSO:H₂O = 1:4, 3 mL	72	74	52 (6.1:1)	91
10	DMSO:H₂O:MeOH = 1:4:3, 4.8 mL	92	>99	94, 90^c(5.4:1)	90
11^d	DMSO:H₂O:MeOH = 1:4:3, 4.8 mL	5	21	trace	—
12^e	DMSO:H₂O:MeOH = 1:4:3, 4.8 mL	—	—	n.r.	—

Fig. 3. Substrate scope of (benzo)furans. Reaction conditions: A mixture of 1a (2 equiv., 0.2 mmol) and 1b-29b (1 equiv., 0.1 mmol), 0.5 mol% Λ-MOC-16, and solvent (4.8 mL, DMSO:H2O:MeOH = 1:4:3) was stirred under N2 for 12-36 h with white LEDs as light source. Isolated yields are shown. Diastereomer ratios (d.r.) were determined by 1H NMR analysis of the crude reaction mixture. Enantiomeric excess (ee) ratios were determined using high performance liquid chromatography (HPLC) analysis. Single-crystal structures of an enantiomeric pair of 10 and 11 as well as 30 are shown in SI. a 0.5 mol% Δ-MOC-16. b3 mmol scale, 56 h.

Fig. 4. Substrate scope of cinnamates and transformation study. Reaction conditions: A mixture of 2a-21a (2 equiv., 0.2 mmol) and 7b (1 equiv., 0.1 mmol), 0.5 mol% Λ-MOC-16, and solvent (4.8 mL, DMSO: H2O: MeOH = 1: 4: 3) was stirred under N2 for 24 h with white LEDs as the light source. Isolated yields are shown. Diastereomer ratios (d.r.) were determined by 1H NMR analysis of the crude reaction mixture. Enantiomeric excess (e.e.) ratios were determined using HPLC analysis. a4 mmol scale, 60 h. Transformation of 36: a, LiOH·H2O, THF/MeOH (2:1), 0 °C; b, LiHMDS, THF, -78 °C; c, 4-methoxyphenylboronic acid, Pd(PPh3)4, Na2CO3, toluene, 80 °C; d, trimethylsilylacetylene, Pd(PPh3)2Cl2, PPh3, CuI, triethylamine, 70 °C.

Fig. 5. Host-guest chemistry and catalytic study. (a) Control experiments between 1a and 7b. Standard conditions: 0.5 mol% Λ-MOC-16, under N2, at room temperature for 16 h, 1a:7b = 2:1, 1 equiv. = 0.1 mmol, DMSO: H2O: MeOH = 1:4:3 (v:v, 4.8 mL), 4 × 5 W white LEDs as light source. aConversion of substrates and yield of products were analyzed by 1H NMR yields of crude products. bEnantiomeric excess (ee) determined by chiral HPLC. (b) Solubilization enhancing effect of MOC-16 (1.04 × 10-4 mol/L) to improve solubilities of representative substrates in aqueous solvent (DMSO: H2O: MeOH = 1:4:3) via phase-transfer driven by host-inclusion. (c) Co-solubility of different substrates (1a + 7b) in solvent (DMSO: H2O: MeOH = 1:4:) with or without MOC-16 (1.04 × 10-4 mol/L). (d) Titration curve fitting with Hill function of 1a and 7b (400 MHz, DMSO-d6: CD3OD: D2O = 1:3:4, v:v:v, 298 K). (e) 1H NMR titration 7b (1-13 equiv.) into a [1a]7⊂MOC-16 host-guest system (400 MHz, DMSO-d6: CD3OD: D2O = 1:3:4, v:v:v, 298 K), showing co-encapsulation of these two different substrates. The proton signals of MOC-16, 1a and 7b are labeled as black, orange and green dots, respectively.

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