Cage-confined photocatalysis for wide-scope unusually selective [2 + 2] cycloaddition through visible-light triplet sensitization

Light-induced [2 + 2] cycloaddition is the most straightforward way to generate cyclobutanes, which are core structures of many natural products, drugs and bioactive compounds. Despite continuous advances in selective [2 + 2] cycloaddition research, general method for intermolecular photocatalysis of acyclic olefins with specific regio- and diastereoselectivity, for example, syn-head-to-head (syn-HH) cyclobutane derivatives, is still lack of development but highly desired. Herein, we report a cage-confined photocatalytic protocol to enable unusual intermolecular [2 + 2] cycloaddition for α,β-unsaturated carbonyl compounds. The syn-HH diastereomers are readily generated with diastereoselectivity up to 99%. The cage-catalyst is highly efficient and robust, covering a diverse substrate range with excellent substituent tolerance. The mimic-enzyme catalysis is proposed through a host-guest mediated procedure expedited by aqueous phase transition of reactant and product, where the supramolecular cage effect plays an important role to facilitate substrates inclusion and pre-orientation, offering a promising avenue for general and eco-friendly cycloaddition photocatalysis with special diastereoselectivity.

MOC-16 containing BF4and PF6anions was prepared following our previously reported procedure 1  Single-crystals of MOC-16 and guestsMOC-16 were carefully picked, coated with paratone oil and attached to a glass fiber, which was inserted in a stainless steel stick. Crystals were quickly mounted to the Agilent Gemini S Ultra CCD Diffractometer with the Enhance X-ray Source of Cu radiation (λ = 1.54184 Å) using the ω-scan technique. All of the structures were solved by direct methods and refined by full-matrix least squares against F 2 using the SHELXL programs. 2 Hydrogen atoms were placed in geometrically calculated positions and included in the refinement process using riding model with isotropic thermal parameters: Uiso(H) = 1.2 Ueq(-CH). All the electrons of disordered solvent molecules which cannot be determined are removed by SQUEEZE routine of PLATON program. 3 Crystal and refinement parameters are listed in Supplementary Table 1, and selected bond lengths (Å) and angles (°) in Supplementary

Single-crystal structures of products 1 and 70.
Diffraction data were collected on an Agilent SuperNova X-Ray diffractometer using micro-focus X-ray sources (Cu-Kα, λ =1.54184 Å). Crystal and refinement parameters are listed in Supplementary Table 5, and selected bond lengths (Å) and angles (°) in Supplementary General procedure for preparation of α,β-unsaturated ketones.

Synthesis of chalcone derivatives
In a 100 mL flask, a solution of aldehyde (15 mmol) in 50 mL methanol at 0 ºC was added aqueous KOH solution (40 mmol in 10 mL H2O) slowly and stirred for 10 min, then ketone was added in portions at 0 ºC.
The reaction was monitored by TLC. After complete consumption of the starting materials, MeOH was removed under reduced pressure. The residue was extracted with EtOAc (3 ⅹ 15 mL). The combined organic phase was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to give the corresponding product.

Synthesis of cinnamic ester derivatives
In a 100mL flask, α,β-unsaturated carboxylic acid (6 mmol) was dissolved in alcohol (20 mL), and H2SO4 (9 mmol) was added in portions. The reaction was stirred at reflux for 16 h then cooled to room temperature.
The mixture was poured into H2O (40 mL) and extracted with EtOAc (3 ⅹ 15 mL). The combined organic phase was washed with saturated aqueous NaHCO3, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography to give the corresponding ester.

Synthesis of enone derivatives
To a 100 mL flask equipped with a stir bar and a condenser was added carboxaldehyde (0.8 mmol), 1-(triphenylphosphoranylidene)-2-propanone (1.12 mmol), and toluene (20 ml). The reaction mixture was refluxed for 10 h. After completion, the reaction mixture was concentrated under reduced pressure. The crude mixture was purified by flash chromatography on silica gel to give the corresponding product.

Absorption and emission spectra of MOC-16 and chalcone
UV-Vis absorption and emission study of MOC-16 and chalcone support the triplet energy transfer mechanism. Exciting MOC-16 with 450 nm light resulted in a broad emission band around 610 nm, which belongs to the 3 MLCT emission of MOC-16 31 and covers the triplet energy area of chalcone (ca. 590 nm) 4 .