Metal–free Decarboxylative Amination: An Alternative Approach Towards Regioselective Synthesis of β‐Carboline N‐fused Imidazoles

Abstract

Due to significant activity profile and natural abundance of b-carboline containing alkaloids, b-carboline N-fused imidazole derivatives were designed and iodine assisted efficient approach was formulated for the regioselective synthesis of designed prototypes via decarboxylative amination of natural a-amino acids with 1-formyl pyrido [3,4-b]indoles. Additionally, oxidative amination with benzyl amines was also investigated for the synthesis of these b-carboline D-ring containing frameworks.

1(3)‐Formyl‐β‐carbolines: Potential Aldo‐X Precursors for the Synthesis of β‐Carboline‐Based Molecular Architectures

“…Recently,S ingh et al developed an efficient iodine-mediated strategy for the regioselective synthesis of N-fused b-carbo-lineÀimidazole derivatives (107)t hrough ad ecarboxylative amination of natural a-aminoa cids with 1-formyl-b-carbolines (7 and 26;S cheme 40). [33] Thiss trategy was also found to be applicable to aw ide variety of a-aminoa cids that contained aromatic,h eteroaromatic, and aliphatic substituents. Interestingly,i nt he case of l-serine, the hydroxy functionality participated in a trans-esterification reaction to yield pentacyclic frameworks (109)t hat contained alactonemoiety.…”

“…Recently,amore-economical pathway for the synthesis of 1formyl-pyrido[3,4-b]indole (7)a nd its N-substituted derivatives (26)w as developed by Singh et al (Scheme 9). [33] Theirs tudy involved the Pictet-Spengler condensation of l-tryptophan (instead of l-tryptophan ester) with 2,2-dimethoxy acetaldehyde to mitigate the limitations of longerr eaction times that were associated with previousp rocedures. At etrahydro-b-carboline (THbC) derivative( 24)w as obtained as ad iastereomeric mixture (10:1) within 1h in 92 %y ield.…”

“…Scheme12. Synthesis of biscarboline-based axially chiral catalysts (32)(33)(34)(35). TCCA = trichloroisocyanuric acid, mCPBA = meta-chloroperoxybenzoic acid, Bn = benzyl.…”

“…In another variation, I 2 -mediated oxidative amination of benzyla mines with 1-formyl-b-carbolines produced N-fused b-carbolineÀimidazole derivatives (107 and 110), albeit in poor yield (Scheme 41). [33] The functionalization of N-fused b-carbolineÀimidazole derivatives (107)w as furtherd emonstrated by treatment with DMF/POCl 3 ,w hich yieldedm ethyl 1-formyl-11-methyl-3-phenyl-11H-imidazo[1',5':1,2]pyrido [3,4-b]indole-5-carboxylates (111; Scheme42).…”

“…[51] The second approachi nvolved the initial condensation of benzyla mine with compounds 26,w hichr esulted in the formationo fi mines 117,f ollowed by N-iodination ands uccessive CÀHo xidation to yield the commoni ntermediate, that is, azomethine ylide 114 or 115.T he in-situ-generated azomethines 115 followed the cascade 6p-electrocyclization processw ith the N2 atom to furnish cyclic intermediates 116 and furtheroxidation afforded compounds 107 followingr oute I, as described in Scheme43. [33]…”