Iron-mediated total synthesis of the cytotoxic carbazole koenoline and related alkaloids

Abstract

The total syntheses of the alkaloids mukonine, murrayanine, and koenoline are described using an iron-mediated arylamine cyclization as the key step. Recently we have shown the efficiency of various (q5-

Efficient Construction of Pyrano[3,2‐a]carbazoles: Application to a Biomimetic Total Synthesis of Cyclized Monoterpenoid Pyrano[3,2‐a]carbazole Alkaloids

“…The iron‐mediated and molybdenum‐mediated approaches afforded 2‐methoxy‐3‐methylcarbazole ( 2 ) in only moderate yields (2 steps, 10 and 28 % overall yield) 29a. 31 Ether cleavage provided compound 1 in 78 % yield 29a. We have now developed two alternative very efficient palladium‐catalyzed routes providing 2‐hydroxy‐3‐methylcarbazole ( 1 ) in 78–85 % overall yield (Scheme ).…”

Domino NH/CH Bond Activation: Palladium‐Catalyzed Synthesis of Annulated Heterocycles Using Dichloro(hetero)arenes

“…Finally, we applied our protocol to an efficient synthesis of naturally occurring murrayafoline A16 ( 3 q ; Scheme 2). Hence, easily accessible 2‐methoxy‐4‐methylaniline21 delivered the desired product 3 q in high yield through the palladium‐catalyzed domino reaction, even when using inexpensive 1,2‐dichlorobenzene.…”

“…Representative procedure—synthesis of murrayafoline A ( 3 q ): A solution of Pd(OAc) 2 (11.2 mg, 0.05 mmol, 5.0 mol %), PCy 3 (28.9 mg, 0.10 mmol, 10 mol %), finely powdered K 3 PO 4 (467 mg, 2.20 mmol), 2‐methoxy‐4‐methylaniline21 (165 mg, 1.20 mmol), and 1,2‐dichlorobenzene (424 mg, 1.20 mmol) in dry NMP (10.0 mL) was stirred for 18 h at 130 °C under N 2 . Et 2 O (25 mL) and H 2 O (25 mL) were added to the reaction mixture at ambient temperature.…”

Transition Metal‐Diene Complexes in Organic Synthesis. Part 15. Iron‐mediated total synthesis of carbazomycin A and B

“…Colorless oil. IR (CHCI,): 3020,2933(CHCI,): 3020, ,1626(CHCI,): 3020, ,1405(CHCI,): 3020, , 1366(CHCI,): 3020, , 1322(CHCI,): 3020, , 1292(CHCI,): 3020, , 1247(CHCI,): 3020, , 1091 1-(2-Methoxy-3,4-dimethylphenyl)ethanone (16). A soh.…”

“…KOH soln. to remove the by-products 14 and 15, dried (MgS04) and evaporated, and the yellow oil distilled at 88-90°/0.8 mbar: 13 (5. (16). A soh.…”