(E)-3-(4-bromophenyl)prop-2-enal

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the product of Example 7.1C (0.676 g, 3.2 mmol) and the product from Example 7.1A (1.0 g, 2.91 mmol) was added ethanol (30 mL) followed by potassium hydroxide (0.163 g, 2.91 mmol), and the mixture was stirred at room temperature for 16 hours. Afterwards the mixture was concentrated. The residue was partitioned between water and ethyl acetate. The organic layers were combined, dried and then concentrated. The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which afforded 150 mg, (10%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 7.37 (m, 3H), 7.32 (d, J=8.5, 2H), 7.21 (d, J=8.4 Hz, 2H), 7.06 (d, J=8.3 Hz, 2H), 6.93 (m, 4H), 6.51 (dd, J=2.9 Hz, 1H), 1.29 (s, 9H). Afterwards the mixture was concentrated The residue was partitioned between water and ethyl acetate dried concentrated The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the product of Example 7.1B (8.35 g, 39.2 mmol) dissolved in dichloromethane (151 mL) was added pyridinium dichromate (22.11 g, 58.8 mmol), and the resultant mixture was stirred for 16 hours at room temperature. A solution of hexane was added, and the resultant mixture filtered through diatomaceous earth, and then concentrated. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layers were combined, dried and then concentrated. The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which afforded 5.5 g, (67%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 9.62 (d, J=7.6 Hz, 1H), 7.57 (d, J=8.5 Hz, 2H), 7.42 (m, 3H), 6.70 (dd, J=15.9, 7.6 Hz, 1H). the resultant mixture filtered through diatomaceous earth concentrated Water was added to the residue the mixture was extracted with ethyl acetate dried concentrated The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the product of Example 7.1C (0.676 g, 3.2 mmol) and the product from Example 7.1A (1.0 g, 2.91 mmol) was added ethanol (30 mL) followed by potassium hydroxide (0.163 g, 2.91 mmol), and the mixture was stirred at room temperature for 16 hours. Afterwards the mixture was concentrated. The residue was partitioned between water and ethyl acetate. The organic layers were combined, dried and then concentrated. The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which afforded 150 mg, (10%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 7.37 (m, 3H), 7.32 (d, J=8.5, 2H), 7.21 (d, J=8.4 Hz, 2H), 7.06 (d, J=8.3 Hz, 2H), 6.93 (m, 4H), 6.51 (dd, J=2.9 Hz, 1H), 1.29 (s, 9H). Afterwards the mixture was concentrated The residue was partitioned between water and ethyl acetate dried concentrated The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the product of Example 7.1B (8.35 g, 39.2 mmol) dissolved in dichloromethane (151 mL) was added pyridinium dichromate (22.11 g, 58.8 mmol), and the resultant mixture was stirred for 16 hours at room temperature. A solution of hexane was added, and the resultant mixture filtered through diatomaceous earth, and then concentrated. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layers were combined, dried and then concentrated. The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which afforded 5.5 g, (67%) of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 9.62 (d, J=7.6 Hz, 1H), 7.57 (d, J=8.5 Hz, 2H), 7.42 (m, 3H), 6.70 (dd, J=15.9, 7.6 Hz, 1H). the resultant mixture filtered through diatomaceous earth concentrated Water was added to the residue the mixture was extracted with ethyl acetate dried concentrated The residue was purified by chromatography (silica gel, hexanes in ethyl acetate) which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared according to the general procedure using (Z)-4-benzylidene-2-(2,5-difluorophenyl)-1H-imidazol-5(4H)-one and (E)-3-(4-bromophenyl)acrylaldehyde. The unpurified residue was purified by flash chromatography using 15% EtOAc/hexanes to afford 11 as a white solid (95 mg, 64%). Analytical data for 11: 1H NMR (500 MHz, CDCl3) δ 9.37 (d, J=8.0 Hz, 1H), 7.89 (ddd, J=9.1, 6.1, 3.2 Hz, 1H), 7.47-7.41 (m, 2H), 7.39-7.30 (m, 3H), 7.09-7.02 (m, 1H), 7.02-6.92 (m, 5H), 4.08 (d, J=6.9 Hz, 1H), 3.56 (ddd, J=9.8, 6.8, 5.0 Hz, 1H), 3.27 (dd, J=14.9, 4.9 Hz, 1H), 2.41 (dd, J=14.9, 9.9 Hz, 1H); 13C NMR (CDCl3, 126 MHz) δ 168.6, 159.1 (d, JCF=243.6 Hz), 155.4 (d, JCF=240.8 Hz), 148.9, 136.9, 136.8, 136.5, 131.7, 130.8, 129.3, 128.4, 127.9, 120.6, 118.3 (dd, JCF=12.4, 9.4 Hz), 117.1 (dd, JCF=25.7, 8.3 Hz), 116.6 (dd, JCF=24.5, 9.6 Hz), 114.5 (dd, JCF=26.9, 3.8 Hz), 110.7 (d, JCF=3.7 Hz), 47.1, 38.5, 32.3; IR (film) cm−1 1773, 1618, 1529, 1481, 1463, 1240, 1171, 1119, 1099, 1071, 1011, 765, 740, 699; LRMS (ESI): Mass calcd for [M+H]+ C25H18BrF2N2O2: 495.0. found 495.0; Enantiomeric ratio was measured by chiral phase HPLC (Chiralcel OD-H; 10% IPA/hexanes; 1.0 mL/min, 280 nm), Rt1 (major)=33.1, Rt2 (minor)=52.8 min; er=96:4. Prepared The unpurified residue was purified by flash chromatography