Efficient iron-mediated approach to pyrano[3,2-a]carbazole alkaloids—first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine, first asymmetric synthesis and assignment of the absolute configuration of (−)-trans-dihydroxygirinimbine

Abstract

Iron-mediated oxidative cyclisation provides an efficient approach to pyrano[3,2-a]carbazole alkaloids. Thus, improved routes to girinimbine and murrayacine as well as the first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine are reported. Asymmetric epoxidation of girinimbine led to (-)-trans-dihydroxygirinimbine and the assignment of its absolute configuration.

Synthesis of Methylene‐Bridged Biscarbazole Alkaloids by using an Ullmann‐type Coupling: First Total Synthesis of Murrastifoline‐C and Murrafoline‐E

“…This second approach started with the oxidation of 9 a by using DDQ to obtain the corresponding aldehyde murrayacine ( 24 ) in 96 % yield (Scheme ) . Boc‐Protection of the carbazole nitrogen atom of 24 followed by reduction of the carbaldehyde to a hydroxymethyl group and activation of the latter as para ‐nitrobenzoate provided 25 in 87 % yield over three steps.…”

“…Subsequently, the same alkaloid was also obtained by others and several synthetic approaches have been developed. We applied a molybdenum‐mediated, an iron‐mediated, and our palladium‐catalysed route to the synthesis of 9 a ,. (+)‐Mahanimbine ((+) ‐9 b ) was isolated for the first time in 1966 by Chakraborty et al.…”

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

“…Under optimized conditions (excess of titanium(IV) tetraisopropoxide), the reaction with 1 led to 3 in 82 % yield (Scheme ). Our three previous approaches to this natural product, all using 5‐amino‐2,2,8‐trimethylaminochromene as building block, provided 3 either via a molybdenum‐mediated synthesis (2 steps, 11 % overall yield),29b a palladium‐catalyzed process (3 steps, 26 % overall yield),30l or an iron‐mediated approach (2 steps, 58 % overall yield) 35. The present route via a palladium‐catalyzed synthesis of 1 and subsequent annulation of the pyran ring affords 3 in 4 steps and 69 % overall yield based on 3‐methoxy‐4‐methylaniline and currently represents the best approach.…”

“…Oxidation with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) using a mixture of methanol, tetrahydrofuran, and water as solvent provided 4 in an improved yield (96 %). In a previous study in cooperation with the group of Professor Katsuki (Kyushu University, Fukuoka, Japan), we have shown that 3 can be transformed into natural (−)‐ trans ‐dihydroxygirinimbine ( 22 ) via asymmetric epoxidation and subsequent hydrolysis (98 % ee ) 35. 36…”

Katsuki Catalysts for Asymmetric Oxidation: Design Concepts, Serendipities for Breakthroughs, and Applications

“…54 The high synthetic utility was further demonstrated by Kishi, 55 Fürstner, 56 and Knölker, 57 who each employed the Ti(Oi-Pr) 4 /K7 R /H 2 O 2 system to prepare a chiral epoxide as the building block for the synthesis of their target natural products, respectively (Scheme 23).…”