Recent Advances and Perspectives in the Synthesis and Applications of Tetrahydrocarbazol‐4‐ones^†

Abstract

Tetrahydrocarbazol‐4‐one represents a prevalent framework of numerous natural products and pharmaceuticals. This review summaries the recent synthetic progresses of this core structure, including Fischer indolization, oxidative and reductive coupling, α‐arylative cyclization by means of transition‐ metal catalysis or under metal‐free conditions, and other methods. The recently emerged enantioselective catalytic methods of tetrahydrocarbazol‐4‐ ones are also described. The mechanistic insights and applications of these strategies as a key step in the total (formal) synthesis of complex alkaloids are highlighted as well.

Divergent Syntheses of Pyridoacridine Alkaloids viaPalladium‐Catalyzed Reductive Cyclization with Nitro‐Biarenes

“…In past decades, the use of nitroarenes or nitroalkenes to synthesize N ‐heterocycles via transition‐metal catalyzed reductive cyclization has progressed rapidly, which leads to directly generating the final products and saving several synthetic steps. [ 9 ] Carbon monoxide is the most frequently employed reductant due to good selectivity and atomic economy. [ 10 ] Recently, CO‐surrogates were developed to overcome the limitation of hazardous pressurized gas manipulation, [ 11 ] but most cases focus on the construction of 5‐membered ring containing heterocycles.…”

Enantioselective Synthesis of α-All-Carbon Quaternary Center-Containing Carbazolones via Amino-palladation/Desymmetrizing Nitrile Addition Cascade

“…Carbazolones are prominent structural motifs found in a large family of biologically important and stereochemically rich indole alkaloids. − To date, total syntheses of more than 10 alkaloids of the Aspidosperma and Kopsia families have been achieved employing carbazolones as key intermediates (Scheme A). − A unique unifying feature of these studies is that multiple topologically differing stereocenters in each target were successfully installed utilizing the C20 all-carbon quaternary center as a stereochemical linchpin, thus highlighting the enabling potential of enantioenriched carbazolones in divergent syntheses toward a wide range of natural products.…”

“…Surprisingly, there are few enantio­selective synthetic methods to access these important α-quaternary center-containing carbazolones . Only two types of asymmetric catalytic approaches have been reported: Pd(0)-catalyzed decarboxylative allylic alkylation and thiourea-catalyzed Michael addition (Scheme B,C).…”

“…Surprisingly, there are few enantioselective synthetic methods to access these important α-quaternary centercontaining carbazolones. 1 Only two types of asymmetric catalytic approaches have been reported: Pd(0)-catalyzed decarboxylative allylic alkylation and thiourea-catalyzed Michael addition (Scheme 1B,C). In 2013, the groups of Shao 14 and Lupton 18 concurrently implemented an enantioconvergent Pd(0)-catalyzed decarboxylative allylic alkylation reaction 28−32 to forge quaternary center-containing carbazolones (Scheme 1B).…”

“…Selected Results of Condition OptimizationDetermined by1 H NMR of the crude mixture using an internal standard. c Determined by HPLC (Chiralpak AD-H).…”