C–H bond activation in the total syntheses of natural products

Direct Integration of Phthalazinone and Succinimide Scaffolds via Rh(III)‐Catalyzed C−H Functionalization

“…3, 161.4, 155.8, 149.2, 144.5, 141.4, 140.2, 137.2, 130.9, 130.0, 129.9, 129.8, 119.9, 116.0, 113.0, 43.8, 38.4, 25.2;IR (KBr) υ 3393, 3328, 3288, 3239, 2943, 2830, 2356, 1698, 1540, 1444 1-(2-(1-Methyl-2,5-dioxopyrrolidin-3-yl)phenyl)-1,2-dihydropyridazine-3,6-dione (3 n): 59.3 mg (99%); white solid; mp = 272.9-275.2°C; 1 H NMR (400 MHz, CDCl 3 /CD 3 OD 10 : 1 v/v) δ 7. 4H),1H),1H),3.96 (dd,J = 9.2,4.8 Hz,1H),3.04 (dd,J = 18.8,9.6 Hz,1H),2.94 (s,3H),2.73 (dd,J = 18.8,3.6 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 /CD 3 OD 10 : 1 v/v) δ 178. 3, 176.4, 159.3, 153.5, 140.1, 134.4, 133.5, 129.8, 128.9, 128.4 (two carbon overlap), 128.1, 42.1, 36.9, 25.0;IR (KBr) υ 3383, 2942, 2831, 1776, 1698, 1595, 1544, 1492, 1437, 1383, 1337, 1281, 1119, 1026 3,179.1,160.3,159.9,142.0,138.0,137.3,134.6,134.4,133.7,131.9,131.8,130.0,…”

“…4H),1H),1H),3.96 (dd,J = 9.2,4.8 Hz,1H),3.04 (dd,J = 18.8,9.6 Hz,1H),2.94 (s,3H),2.73 (dd,J = 18.8,3.6 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 /CD 3 OD 10 : 1 v/v) δ 178. 3, 176.4, 159.3, 153.5, 140.1, 134.4, 133.5, 129.8, 128.9, 128.4 (two carbon overlap), 128.1, 42.1, 36.9, 25.0;IR (KBr) υ 3383, 2942, 2831, 1776, 1698, 1595, 1544, 1492, 1437, 1383, 1337, 1281, 1119, 1026 3,179.1,160.3,159.9,142.0,138.0,137.3,134.6,134.4,133.7,131.9,131.8,130.0,129.9,128.8,128.2 (q,127.4,127.3,124.8 (q, J C-F = 271.5 Hz), 38.6, 25.0 (two carbon overlap); IR (KBr) υ 3466, 3071, 3004, 2953, 2364, 2345, 1775, 1694, 1641, 1606, 1557, 1516, 1474, 1360, 1223, 1165, 1061, 989, 862, 838, (400 MHz, CD 3 OD) δ 8.35 (dd, J = 7.8, 1. 5 Hz,1H), 8.14-8.12 (m, 1H), 7.96-7.88 (m, 2H), 7.51-7.43 (m, 2H), 7.51-7.39 (m, 2H), 4.22 (dd,...…”

“…As a consequence, these methods can lead to the lessening of synthetic steps for natural products and useful building blocks. [3] Moreover, the late-stage CÀ H functionalization into bioactive molecules can offer new opportunities to discover improved physical and pharmacological properties. [4] Although these types of catalytic CÀ H functionalizations have been well studied, the direct integration of two bioactive scaffolds to generate new bioactive compounds has rarely been explored to date.…”

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

“…This synthesis is a beautiful demonstration of the successful merger of classic, scalable carbonyl-based chemistry combined with cutting-edge C-H activation synthetic methodology. 125–130 …”

“…Overall this 9-step route to 149 proceeded in an impressive 14% overall yield, further demonstrating the power of C(sp 3 )–H bond oxidation in the synthesis of complex terpenoids. 125–130,184 …”