A High Loading and Recyclable Pentaerythritol Supported Imidazolidin-4-One Catalyst For

Supporting Information

A high loading and recyclable pentaerythritol supported imidazolidin-4-one catalyst for enantioselective Diels-Alder reactions

Kaitao Du, Cuifen Lu*, Zuxing Chen, Junqi Nie, Guichun Yang*

Hubei Collaborative Innovation Center for Advanced Organochemical Materials Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, China

*Email: , , Tel: +86 27 5086 5322

1. General

Reactions were monitored by TLC using precoated plates of silica gel HF254 (0.5 mm, Yantai, China). Column chromatography was performed with a silica gel column (200-300 mesh, Yantai, China). NMR spectra were recorded on WIPM 400 spectrometer (1H at 400 MHz, 13C at 100 MHz). IR spectra were recorded on an IR-spectrum one (PE) spectrometer. High-resolution mass spectra (HRMS) were recorded on Agilent 1260-6224 LC-MS TOF using ESI (electrospray ionization). Enantioselectivity were determined by HPLC ( Dionex UltiMate 3000 ) analysis employing a Daicel ChiralCel OD-H, ChiralPak AS-H columns and Chiralcel OJ-RH . A UV detector (UVD-3000) was used for the peak detection.

2. Experimental Method

2.1 General procedure for synthesis of pentaerythritol supported chiral imidazolidin-4-ones I–II

To a solution of compound 3 (1.0 g, 1.3 mmol) or compound 4 (1.0 g, 0.87 mmol) in dry DMF (10 mL) was added imidazolidin-4-one 1 (1.6 g, 6.8 mmol) and Cs2CO3 (6.1 g, 19.5 mmol) at room temperature. After stirring at 80 °C for 30 h, the mixture was evaporated under vacuum, then the residue was dissolved in the minimum amount of CH2Cl2 (2 mL) and slowly poured into Et2O (30 mL). The precipitate was filtered on Celite, washed with 10 mL of Et2O and dried under vacuum to obtain I or II as a white solid. Catalyst I (1.12g, 85%); Catalyst II (1.0 g, 74%).

2.2 Synthesis of pentaerythritol supported chiral imidazolidin-4-one III

Compound 5 (0.2 g, 0.85 mmol), compound 2 (1.85 g, 6.8 mmol) and dry THF (10 mL) were charged to a 25 mL three-neck round-bottomed flask equipped with a magnetic stirrer. The system was degassed and purged with nitrogen, then CuBr (24 mg, 0.17 mmol) and N,N,N′,N′′,N′′′-pentamethyldiethylenetriamine (PMDETA) (35 μL, 0.17 mmol) were added. The reaction mixture was stirred at room temperature for 20 h and dropped into dilute HCl (1 wt.%, 20 mL). The resultant mixture was extracted with CH2Cl2 (20 mL×3), dried over Na2SO4, and concentrated under vacuum to about 2 mL, and slowly poured into Et2O (30 mL). The precipitate was filtered on Celite, washed with 10 mL of Et2O and dried under vacuum to obtain III as a white solid (0.96 g, 86%).

2.3 Charactrization of catalyst I

IR (NaCl): υ 3297, 2972, 1682, 1511, 1236, 1034 cm-1; 1H NMR (400 MHz, CDCl3): δ 7.11 (d, J=7.2 Hz, 8H, ArH), 6.82 (d, J=7.2 Hz, 8H, ArH), 4.25 (s, 8H, CH2O), 3.72 (t, J=5.6 Hz, 4H, COCH), 3.06 (dd, J=4.2, 14.4 Hz, 4H, PhCH), 2.96 (dd, J=6.8, 14.4 Hz, 4H, PhCH), 2.72 (s, 12H, NCH3), 1.24 (s, 12H, CCH3), 1.16 (s, 12H, CCH3); 13C NMR (100 MHz, CDCl3): δ 173.21, 157.73, 130.52, 129.15, 114.73, 75.67, 66.32, 59.25, 44.57, 35.91, 27.13, 25.05.

HRMS (ESI) calcd for C57H77N8O8 [M+H]+: 1001.5864, found 1001.5929.

1H NMR spectrum of I (400 MHz, CDCl3)

Superimposed 1H NMR spectrum of the fourth recovered catalyst I and unused catalystⅠ(400 MHz, CDCl3)

13C NMR spectrum ofⅠ (100 MHz, CDCl3)

Mass Spectrometry of I

2.4 Charactrization of catalyst II

IR (NaCl): υ 3331, 2928, 1682, 1511, 1237, 1040 cm-1; 1H NMR (400 MHz, CDCl3): δ 7.07 (d, J=7.2 Hz, 12H, ArH), 6.82 (d, J=7.2 Hz, 12H, ArH), 4.07 (s, 12H, CH2O), 3.78 (s, 4H,CCH2O)，3.72 (t, J=5.6 Hz, 6H, COCH), 3.07 (dd, J=4.4, 14.4 Hz, 6H, PhCH), 2.96 (dd, J=6.0, 14.4 Hz, 6H, PhCH), 2.74 (s, 18H, NCH3), 1.24 (s, 18H, CCH3), 1.17 (s, 18H, CCH3); 13C NMR (100 MHz, CDCl3): δ 173.52, 157.77, 130.46, 129.33, 114.67, 75.58, 66.74, 59.32, 44.92, 36.91, 27.15, 25.36, 25.14.

HRMS (ESI) calcd for C88H119N12O13 [M+H]+: 1551.9020, found 1551.9107.

1H NMR spectrum of Ⅱ (400 MHz, CDCl3)

13C NMR spectrum of Ⅱ (100 MHz, CDCl3)

Mass Spectrometry of Ⅱ

2.4 Charactrization of Catalyst III

IR(NaCl): υ 2973, 1682, 1511, 1237, 1049 cm-1;. 1H NMR (400 MHz, DMSO-d6): δ 8.40 (s, 4H,CCH), 7.16 (d, J=7.8 Hz, 8H, ArH), 6.94 (d, J=7.8 Hz, 8H, ArH), 5.14 (s, 8H, CH2O), 4.54 (s, 8H,CCH2O), 3.54 (t, J=7.8 Hz, 4H, COCH), 2.93 (dd, J=2.8, 14.4 Hz, 4H, PhCH), 2.64 (s, 12H, NCH3), 2.57 (dd, J=9.8, 14.4 Hz, 4H, PhCH), 1.18 (s, 12H, CCH3), 1.16 (s,12H, CCH3); 13C NMR (100 MHz, DMSO-d6): δ 173.39, 156.94, 143.26, 131.72, 130.72, 75.61, 59.73, 25.24, 23.57.

HRMS (ESI) calcd for C69H89N20O8 [M+H] +: 1325.7172, found 1325.7248.

1H NMR spectrum of III (400 MHz, DMSO-d6)

13C NMR spectrum of III (100 MHz, DMSO-d6)

Mass Spectrometry of III

3. General procedure for the Diels–Alder reaction

To a solution of catalyst I (50 mg, 0.05 mmol, 0.2 mmol catalyst monomer) in CH3CN/H2O (1 mL, 95:5, v/v), 0.4 M HClO4 (0.5 mL, 0.2 mmol) was added, and the mixture was stirred for 5 min at 25 °C. Freshly distilled cinnamaldehyde (0.13 mL, 1.0 mmol) and cyclopentadiene (0.33 mL, 4.0 mmol) were added respectively, and the resulting mixture was stirred at 25 °C for 12-48 h. MgSO4 was then added, after 2 h the mixture was filtered, and the organic solvent evaporated under vacuum. The residue was dissolved in the minimum amount of CH2Cl2 (2 mL) and then poured into Et2O (30 mL). The precipitate was filtered, washed with Et2O (10 mL), dried under vacuum and reused in further reactions as the recycled catalyst. The filtrate was concentrated under vacuum and purified by silica gel column chromatography using petroleum ether and ethyl acetate as eluant to afford the desired product. The endo/exo ratio was determined by 1H NMR spectroscopy of the crude mixture and the enantiomeric excess (ee) of the adduct was determined by HPLC on a chiral phase according to the established procedure [1]. All the products are known compounds and all the spectroscopic data matched those reported in the literature [2,3].

Endo-3-methylbicyclo[2.2.1]heptane-2-carbaldehyde and exo-3-methylbicyclo [2.2.1]heptane -2-carbaldehyde (Table 2 Entry 1)

Enantiomeric ratio was determined by HPLC using Chiracel OD-H column after reaction with N,N-diphenylhydrazone/EtOH (hexane/2-propanol:95/5, 1 mL/min flow rate,λ=254 nm), for endo isomers tR1= 15.54 min (major) and tR2=18.05 min (minor enantiomer), for the exo isomer: TR1=24.93 min (major),TR2=26.52 min (minor).

1H NMR spectrum (400 MHz, CDCl3)