Porous Carbon Nanosheet‐Supported Chiral Squaramide for Highly Enantioselective Friedel–Crafts Reaction

Abstract

Porous carbon nanosheets (PCNs) wereu sed for the first time as as upport to immobilize aq uinine-squaramide catalyst for the asymmetric Friedel-Craftsa ddition of pyrazolonest oi satin ketimines. Relying on its open structure with am acroporous network as well as hydrophobicity,t he PCN-supported catalyst presented catalytic performance comparable to its homogeneous catalyst;t he products were obtained in high yields (up to 90 %) with high ee values (up to 99 %). Recycling batch reactions together with ac ontinuous flow process confirmedt he stabilityo ft he catalyst.The heterogenization of homogeneous chiral catalysts is considered an effective approach towards sustainable asymmetric synthesis. [1] This strategy can providee asily recyclable solid catalysts with clearly known actives ites similar to their homogeneous counterparts. Nevertheless,h eterogenized chiral catalysts achievedb yt he surfacec ovalentt ethering strategy usually exhibit poor enantioselectivity owing to limited free space for chiral induction [2] and uncontrolled activity owing to certain side reactions initiated by the supports. Hence, the structural features and physicochemical properties of catalyst support materials are criticalt od etermine the performance of heterogenizedc atalysts.

Enantioselective Organocatalytic Mannich Reaction and Fluorination Sequence of Pyrazolones to Isatin‐derived Ketimines

“…tert ‐Butyl ( S )‐1‐benzyl‐3‐(( R )‐4‐fluoro‐3‐(naphthalen‐2‐yl)‐5‐oxo‐1‐phenyl‐4,5‐dihydro‐1 H ‐pyrazol‐4‐yl)‐2‐oxoindolin‐3‐ylcarbamate ( 3i ): Brown solid, m.p. 155–158 °C; [α] 28 D = −47.4 (c = 0.84, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.96–7.94 (m, 2H), 7.69 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.51–7.38 (m, 7H), 7.33–7.22 (m, 8H), 6.97 (t, J = 6.8 Hz, 1H), 6.59 (t, J = 7.6 Hz, 1H), 5.82 (d, J = 7.2 Hz, 1H), 4.84 (s, 1H), 4.26 (d, J = 15.6 Hz, 1H), 1.26 (s, 9H); 13 C NMR (100 MHz, CDCl 3 ) δ 171.9 (d, J = 7.6 Hz), 165.9 (d, J = 22.9 Hz), 153.7, 152.1 (d, J = 12.4 Hz), 143.1, 136.5, 134.9, 133.4, 132.1, 130.2, 129.1, 128.8, 128.6, 128.2, 127.9, 127.6, 127.4, 127.4, 126.6, 126.3, 126.2, 125.5, 123.0, 122.8, 120.1, 108.6, 92.2 (d, J = 212.6 Hz), 80.7, 66.5 (d, J = 22 Hz), 44.4, 28.0; 19 F NMR (376.17 MHz, CDCl 3 ) δ −177.99.…”

“…tert ‐Butyl ( S )‐1‐benzyl‐5‐fluoro‐3‐(( R )‐4‐fluoro‐3‐methyl‐5‐oxo‐1‐phenyl‐4,5‐dihydro‐1 H ‐pyrazol‐4‐yl)‐2‐oxoindolin‐3‐ylcarbamate ( 3j ): Bright yellow solid, m.p. 175–178 °C; [α] 28 D = 230.3 (c = 0.80, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.82–7.80 (m, 2H), 7.46–7.42 (m, 2H), 7.34–7.26 (m, 11H), 7.05–6.96 (m, 1H), 6.72 (dd, J = 8, 3.6 Hz, 1H), 5.09 (d, J = 15.2 Hz, 1H), 4.63 (d, J = 16.8 Hz, 1H), 1.34 (s, 9H), 1.23 (d, J = 1.2 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 170.9 (d, J = 7.7 Hz), 165.2 (d, J = 21 Hz), 159.5 (d, J = 242.2 Hz), 153.9, 153.2 (d, J = 15.3 Hz), 139.4, 136.3, 134.9, 129.1, 128.8, 128.1, 127.9, 126.4, 119.7, 116.8 (d, J = 23.8 Hz) 113.9, 113.7, 109.8 (d, J = 7.6 Hz), 90.6 (d, J = 207.8 Hz), 81.1, 65.3 (d, J = 21.9 Hz), 44.8, 28.1, 14.1; 19 F NMR (376.17 MHz, CDCl 3 ) δ −118.65, −181.83.…”

“…The development of new approaches for the construction of vicinal quaternary stereogenic carbon centers is an ongoing topics in synthetic organic chemistry . Recently, Wang and co‐workers reported the asymmetric Friedel–Crafts addition and electrophilic fluorination sequence of pyrazolones to isatin‐derived ketimines and a subsequent fluorination catalyzed by quinine‐derived organocatalyst . Although this approach is moderately satisfied, new organocatalytic asymmetric Mannich reaction and electrophilic fluorination sequence of pyrazolones to isatin‐derived ketimines is highly desired.…”

Recent Advances in Continuous‐Flow Enantioselective Catalysis

“…Meanwhile, the unique two‐dimensional units provide delivery channels and maintain the chiral environment for the catalysts. Thus, PCN‐grafted chiral catalyst 39 was used by Lu and co‐workers for the highly enantioselective Friedel–Crafts reaction of pyrazolones 40 with isatin ketimines 41 (Scheme a). The PCN‐supported quinine‐based squaramide catalyst was shown to work efficiently in five recycling runs and afforded 90 % yields and 99 % ee values.…”

Recent Advances in Squaramide‐Catalyzed Asymmetric Mannich Reactions

“…Squaramide-derived bifunctional hydrogen-bonding catalysts have been developed and applied to a range of asymmetric reactions, including Aza-Morita-Baylis-Hillman reactions, [15] Friedel-Crafts reactions, [16] Aldol reactions, [17] Michael addition reactions, [18] Strecker reactions [19] and so on. β-Amino carbonyl compounds are important parts of pharmaceutical intermediates [20] ( Figure 3) and most of them do not exist in the nature.…”