Vanadium(V) Complex-Catalyzed One-Pot Synthesis of Phenanthridines via a Pictet-Spengler-Dehydrogenative Aromatization Sequence

Abstract

Phenanthridine and its derivatives are important structural motifs that exist in natural products, biologically active compounds, and functional materials. Here, we report a mild, one-pot synthesis of 6-arylphenanthridine derivatives by a sequential cascade Pictet-Spengler-dehydrogenative aromatization reaction mediated by oxovanadium(V) complexes under aerobic conditions. The reaction of 2-(3,5-dimethoxyphenyl)aniline with a range of commercially available aryl aldehydes provided the desired phenanthridine derivatives in up to 96% yield. The ability of vanadium(V) complexes to function as efficient redox and Lewis acid catalysts enables the sequential reaction to occur under mild conditions.

Efficient synthesis of new 6-arylphenanthridines based on microwave-assisted Suzuki–Miyaura cross-coupling and Pictet–Spengler dehydrogenative cyclization in a zinc chloride/[Bmim]BF4 mixture

“…According to the reported methods, the construction of a phenanthridine core is achieved through the following synthetic models (Fig. 2): (1) C Ar -C Ar bond formation via intramolecular cyclization of functionalized imines or anilines or by transitionmetal-catalysed coupling of ortho-halogenated amines/imines with aryl halides or triflates 12,13 (model 1); (2) C Ar -N bond formation of the respective ortho-biaryl keto and aldoximes [14][15][16][17] (model 2); and (3) C-C bond formation through intramolecular cyclization of ortho-aryl isocyanides [18][19][20] or C Ar -C ymine bond formation through intramolecular cyclization of ortho-arylimines (amines, imines or amides) [21][22][23][24][25][26] (model 3). The latter disconnection type includes the well-known Bischler-Napieralski and Pictet-Hubert type cyclization reactions, which are primary methods for phenanthridine preparation using N-acylbiphenyl-2-amine derivatives.…”

“…2c). 23 In this case, the starting 1,1′-biphenyl-2-amine 4a used did not undergo structural modifications for the functionalization of the final products. Moreover, a certain drawback of this methodology is the reaction time required to give way to these phenanthridine derivatives, and despite excellent yields, the use of an asymmetric vanadium( v ) catalyst in this technique is not well understood.…”

“…Having strategic precursors 4a–b in our hands and based on the analysed results of the above-mentioned studies 21,23 and our own experience, 28,29 we wanted to test the Pictet–Spengler reaction of 1,1′-biphenyl-2-amine derivative 4a and benzaldehyde 5a in a 1 : 1 molar ratio under choline chloride-based deep eutectic solvents (ChCl-DESs), 31,32 such as (ChCl)/ZnCl 2 DES, and much more environmentally friendly conditions to obtain the respective C6-phenyl substituted phenanthridine 6a (Table 1).…”

9,10‐Phenanthrenedione‐Catalyzed, Visible‐Light‐Promoted Radical Intramolecular Cyclization of N‐Biarylglycine Esters: One‐Pot synthesis of Phenanthridine‐6‐Carboxylates

“…Phenanthridine [1] and its derivatives are important structural motifs found in naturally occurring alkaloids, [2] metabolites of plants, [3] agrochemicals, [2–3] synthetic dye‐stuff, [4] pharmaceuticals, [5] and functional materials [6] . In fields of medicinal‐ and pharmaceutical chemistry, phenanthridine structures are present in a wide range of synthetic pharmacological compounds that show antitumor, antiviral, antibacterial, antiseptic, DNA intercalation, etc [7] .…”

“…Phenanthridine [1] and its derivatives are important structural motifs found in naturally occurring alkaloids, [2] metabolites of plants, [3] agrochemicals, [2][3] synthetic dye-stuff, [4] pharmaceuticals, [5] and functional materials. [6] In fields of medicinal-and pharmaceutical chemistry, phenanthridine structures are present in a wide range of synthetic pharmacological compounds that show antitumor, antiviral, antibacterial, antiseptic, DNA intercalation, etc. [7] For these reasons, diverse synthetic methodologies include i) metal-catalyzed cross-coupling reactions [8] (Scheme 1), ii) a tandem radical additioncyclization reaction of 2-(1-azidovinyl)-1,1'-biaryls [9] and 2isocyanobiphenyls [10] with diverse radical precursors (Scheme 1) as well as iii) the oxime esters' NÀ O bond homolysis cyclization reactions [11] and oxime ethers [12] (Scheme 1) have been established for phenanthridines preparation.…”