Pepsin-Catalyzed Asymmetric Cross Aldol Reaction Promoted by Ionic Liquids and Deep Eutectic Solvents

Direct Asymmetric Aldol Reaction in Continuous Flow Using Gel‐Bound Organocatalysts

“…(2S,10R)‐2‐[Hydroxy(3‐nitrophenyl)methyl]cyclohexan‐1‐one [24,27–30] ( Table 2 entry 2): Yield 11.0 mg (0.044 mmol, 93 %); anti / syn =68/32, enantiomeric excess: 57 % ( anti diastereomer) determined by HPLC (Daicel Chiralpak IA column; i PrOH/heptane=5 : 95; 0.8 mL/min; 15 °C; λ =254 nm, t R1 =29.9 min, t R2 =38.8 min). 1 H NMR (700 MHz, CDCl 3 ): δ=1.33–1.45 (m, 1H), 1.51–1.62 (m, 3H), 1.79–1.86 (m, 1H), 2.06–2.17 (m, 1H), 2.32–2.42 (m, 1H), 2.47–2.53 (m, 1H), 2.59–2.66 (m, 1H), 3.98–4.25 (s, 1H), 4.89 (d, 3 J HH =8.48 Hz, 1H), 7.53 (t, 3 J HH =7.52 Hz, 1H), 7.65–7.69 (m, 1H), 8.15–8.18 (m, 1H), 8.19–8.23 (m, 1H) ppm.…”

“…(4R)‐4‐(4‐Nitroophenyl)‐4‐hydroxy‐4 butan‐2‐one [24,27–30] ( Table 2 entry 7 ): Yield 8.05 mg (0.038 mmol, 80 %); enantiomeric excess: 19 % ( R‐isomer) determined by HPLC (Daicel Chiralpak IC column; i PrOH/heptane=10 : 90; 0.7 mL/min; 15 °C; λ =254 nm, t R1 =23.9 min, t R2 =25.4 min). 1 H NMR (700 MHz, CDCl 3 ): δ=δ (ppm)=2.22 (s, 3H), 2.79–2.91 (m, 2H), 3.40–3.52 (m, 1H), 5.23–5.29 (m, 1H), 7.54 (d, 3 J HH =8.5 Hz, 2H), 8.21 (d, 3 J HH =8.7 Hz, 2H) ppm.…”

“…1 [24,[27][28][29][30] (Table 2 [24,[27][28][29][30] (Table 2 entry 2 [24,[27][28][29][30] (Table 2 entry 3 [24,[27][28][29][30] (Table 2 entry [24,[27][28][29][30] (Table 2 entry 5): Yield 7.0 mg (0.029 mmol, 63 %); anti/syn = 25/75, enantiomeric excess: 67 % (syn diastereomer) determined by HPLC (Daicel Chiralpak IA column; iPrOH/heptane = 5 : 95; 0.5 mL/min; 15°C; λ = 254 nm, t R1 = 42.7 min, t R2 = 48.8 min). 1 [24,[27][28][29][30] (Table 2 entry 6 (m, 1H), 7.88 (d, 3 J HH = 7.9 Hz, 1H), 7.96-8.01 (m, 1H) ppm. 13 (4R)-4-(4-Nitroophenyl)-4-hydroxy-4 butan-2-one [24,[27][28][29][30] (Table 2 entry 7): Yield 8.05 mg (0.038 mmol, 80 %); enantiomeric excess: 19 % (R-isomer) determi...…”

“…1 [24,[27][28][29][30] (Table 2 entry 6 (m, 1H), 7.88 (d, 3 J HH = 7.9 Hz, 1H), 7.96-8.01 (m, 1H) ppm. 13 (4R)-4-(4-Nitroophenyl)-4-hydroxy-4 butan-2-one [24,[27][28][29][30] (Table 2 entry 7): Yield 8.05 mg (0.038 mmol, 80 %); enantiomeric excess: 19 % (R-isomer) determined by HPLC (Daicel Chiralpak IC column; iPrOH/ heptane = 10 : 90; 0.7 mL/min; 15°C; λ = 254 nm, t R1 = 23.9 min, t R2 = 25.4 min). 1…”

Combination of Enzymes and Deep Eutectic Solvents as Powerful Toolbox for Organic Synthesis

“…The enantioselectivity of the reaction was comparable to the same reaction performed with VOCs instead of DESs [ 124 ]. It should also be reported that another reaction involving carbonyl groups, the aldol reaction, was investigated in its enzymatic version in some DESs, in the framework of a study which was, however, rather focused on the application of imidazolium-based ionic liquids [ 125 ].…”