General Au‐Catalyzed Benzannulation Towards Naturally Occurring Carbazole Alkaloids from Methoxypropadiene

Abstract

Accessible alkaloids: Naturally occurring carbazole alkaloids, such as clauszoline‐K, ‐L, ‐M, and ‐N, 3‐formyl‐7‐hydroxycarbazole, and siamenol, were synthesized through a gold‐catalyzed cyclization reaction of 1‐(indol‐2‐yl)‐2‐methoxy‐2,3‐allenols, which are readily available from indolecarbaldehydes and methoxypropadiene (see scheme; R1=Me, carboxylic acid/ester, or aldehyde; R2=prenyl or H; R3=H or Me). The reaction demonstrates atom economy, high selectivity, and high yields, mostly with catalytic reactions.

Gold‐Catalyzed Functionalization Reactions of Indole

“…[141] With regard to indole alkaloids, in 2011 Ma and co-workers reported the gold(I)-chloride-catalyzed carbocyclization of 2,3-allenols 123 to carbazoles 124 as key step in the total synthesis of siamenol and clauszoline K,L or clausine M derivatives (Scheme 50). [142] Scheme 50. Gold-catalyzed carbocyclization of 123 as key step in the synthesis of siamenol and clauszoline K,L or clausine M derivatives.…”

Transition Metal‐Catalyzed Benzannulation towards Naturally Occurring Carbazole Alkaloids

“…For the purpose of synthesizing the naturally occurring carbazole, a methoxy group has been introduced to the 2‐position of the starting 1‐(indol‐2‐yl)‐2,3‐allenols. We observed that AuCl is a much more effective catalyst than PtCl 2 . In the total synthesis of siamenol, we utilized this transformation as the key step for constructing the carbazole skeleton from the required methoxy‐substituted allenol 1 a .…”

“…The reaction occurred smoothly at room temperature to afford a series of poly‐substituted carbazoles. Two years later, our further investigation led to the observation of AuCl as a much more effective catalyst for this transformation . Due to the easy availability of the starting materials, this simple and mild Au‐catalyzed reaction of 1‐(indol‐2‐yl)‐2,3‐allenols provides a general route to differently substituted carbazoles.…”

Regioselective Synthesis of Elusive 4,9-Dihydro-1H-Carbazoles by Gold-Catalyzed Cycloisomerization of 3-Allenylmethylindoles

“…[34][35][36] In particular, a gold-catalyzed hydroarylation of N-allenylmethylindoles that furnishes dihydro-pyrido[1,2-a]-1H-indoles has been described (Scheme 1a). 37 Moreover, several cyclizations of 1-(indol-2-yl)-allenols (functionalized 2-allenylmethylindoles) that afford carbazoles have been developed using different metals such as Au, [38][39][40] Pt [41][42][43] or Pd 44 (Scheme 1b).…”