Tandem Catalysis of an Aldol-‘Click’ Reaction System within a Molecular Hydrogel

A heterogeneous supramolecular catalytic system for multicomponent aldol-‘click’ reactions is reported. The copper(I) metallohydrogel functionalized with a phenyltriazole fragment was able to catalyze the multicomponent reaction between phenylacetylene, p-nitrobenzaldehyde, and an azide containing a ketone moiety, obtaining the corresponding aldol products in good yields. A possible mechanistic pathway responsible for this unexpected catalytic behavior has been proposed.


Synthesis of Compound II
Compound II was synthesized as previously reported [1].

Synthesis of Compound III
A solution of I (1 g, 3.67 mmol) in THF (15 mL) was added dropwise to a solution of II (2.133 g, 8.08 mmol) in THF (10 mL) under N2 at rt. After stirring for 2 h, the resultant precipitate was filtered, washed with 0.1 M NaOH (10 mL) and water (20 mL), and dried under vacuum, affording III as a white solid. The compound was directly used in the next step without further purification.

Synthesis of Compound IV
A solution of compound III (0.860 g, 1.508 mmol) in DMF (10 mL) was added to a suspension of NaN 3 (0.980 g, 15.08 mmol) in DMF (10 mL) and heated under N 2 to 80 °C overnight. After cooling to rt, the crude was poured into cold water and the resultant precipitate filtered, washed with water (10 mL) and dried under vacuum, obtaining N3Val3N3 as a bright brown solid (0.425 g; 57%). Characterization: 1

Synthesis of Compound 1
Compound 1 was synthesized as previously reported [2].

Synthesis of Compound 6
Acetoazide (0.2 g; 2.03 mmol; 0.181 mL) and phenylacetylene (0.228 g; 2.23 mmol; 0.245 mL) were dissolved in 1:1 t-BuOH:H2O (4 mL). To this solution, CuSO4·5H2O (0.050 g; 0.203 mmol) and sodium ascorbate (0.161 g; 0.812 mmol) were added, and the mixture stirred for 16 h at room temperature. EtOAc (20 mL) was added to the crude product and the organic phase washed with a saturated solution of NaHCO3 (3 × 5 mL) and brine (3 × 5 mL). The organic extracts were dried over anhydrous MgSO4 and the solvents removed on the rotavapor to give a pale yellow solid (0.31 g; 76%). Characterization: 1 Figure S10. Typical 1 H-NMR spectrum of a catalytic reaction in the presence of 10 mol% Cu(I)-PhTzVal 3 (CDCl3, 300 MHz). Figure S11. High-resolution mass spectrometry of the final product, isolated by type II alumina column chromatography of the crude belonging to the three component reaction carried for 2 days in the presence of 10 mol % Cu(I)-PhTzVal3.