Palladium-Mediated Oxidative Annulation of δ-Indolyl-α,β-Unsaturated Compounds toward the Synthesis of Cyclopenta[b]indoles and Heterogeneous Hydrogenation To Access Fused Indolines

Abstract

The cyclopenta­[b]­indole moiety represents a key skeletal unit in several natural and synthetic compounds that exhibit diverse biological properties. We described herein a two-step sequence for synthesizing cyclopenta­[b]­indoles with great structural diversity in overall yields up to 37%. The key step was a palladium-catalyzed oxidative annulation of 3-alkylindoles (Fujiwara–Moritani reaction). The obtained cyclopenta­[b]­indoles were used as substrates in heterogeneous hydrogenation reactions to afford new fused indolines in moderate yields. An acid-catalyzed intramolecular cyclization of three such indolines gave tetracyclic lactams in 89, 90, and 61% yields.

Acyclic Twisted Amides

“… ,− As expected, comparatively fewer examples of structurally characterized N-pyramidalized amides embedded in six-membered rings have been reported; however, these amides feature significant N-pyramidalization (average χ N of 46.1°), while twist is much lower (average τ of 11.2°). These values compare well with the five-membered fused ring lactams (χ N , 45.9°; τ, 11.7°), − ,− …”

“…Similar to β-lactams, the amide bond geometry of structurally characterized amides embedded in a fused five-membered ring system (Figures –) − ,− can be characterized as N-pyramidalized (average χ N of 45.9°) with minimal twist (average τ of 11.7°). As expected, the average values of N-pyramidalization and twist are slightly lower as compared to β-lactams ...…”

“…Most common in this class (Figures –) − ,− is ring fusion to six-membered rings in a [ 3 .4.0] scaffold, including piperazine, such as 4.120 , and hexahydropyrimidine, such as 4.121 , and much more common [ 3 .3.0] ring system with the ring fusion to five-membered rings, including pyrrolidine, such as 4.122 , thiazolidine, such as 4.123 ,…”

“…This class also includes benzo-fused lactams, such as 4.140 , 4.146 , and 4.173 , and tricyclic fused ring systems, such as 4.138 , 4.171 , 4.172 , and 4.181 . In general, increased substitution at the α-position to the nitrogen atom and additional constraints of the five-membered ring, such as unsaturation, conformationally rigid ring systems, and steric effects, lead to higher N-pyramidalization. − ,− …”

Construction of Alkylidene Fluorene Scaffolds Using Pd-Catalyzed Direct Arene/Alkene Coupling Strategy

“…The Pd­(II)-catalyzed Fujiwara-Moritani oxidative arene olefination has been considered as one of the most attractive arene/alkene coupling reactions because it does not require directing groups or the prefunctionalization of both arene and olefin moieties . In particular, the Pd­(II)-catalyzed intramolecular oxidative annulations of electron-rich indole and alkene moieties tethered by alkyl chains have been developed, which afford various indole-fused polyheterocycles based on the substituents at the alkenyl terminus (Scheme b) . However, the use of such strategies in the synthesis of AF-based PAHs and PHAs has been rarely reported.…”