Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• the condensation of easily accessibly 2-(5-methylfuran-2-yl)ethanamine with commercially available aromatic aldehydes followed by acid-catalyzed Pictet–Spengler cyclization. Using this approach, we synthesized a range of 4-substituted tetrahydrofuro[3,2-c]pyridines in reasonable yields. The reactivity

• -c]pyridines. Moreover, multistep cascade processes with the simultaneous construction of several cores were described, where the key step is the generation of an acyliminium cation and the Pictet–Spengler cyclization [30][31][32], including solid-phase synthesis [33][34][35]. Another route for the

• optimized reaction conditions, in addition to the desired tetrahydrofuro[3,2-c]pyridine (4h), led to the major formation of the corresponding 1,4-diketone 5h. This unexpected formation of 3-(2-oxopropyl)piperidin-4-one (5h) led us to the idea that the tandem sequence Pictet–Spengler cyclization/furan acid

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• utilization of the ethoxycarbonyl group for phenol protection. The main objective of this concept was, that after successful N-acyl-Pictet–Spengler cyclization two remaining pairs of transformations might be performed in one single transformation each: route A comprises reduction with lithium alanate, and

• ] demonstrated that this building block is compatible with N-acyl-Pictet–Spengler cyclization conditions. The structures of the utilized building blocks are shown in Figure 4. The N-acyl-Pictet–Spengler cyclizations of appropriate pairs of the building blocks with TFA in dichloromethane at 0 °C for 19–90 h (TLC

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• C1 position. Analogously to the Pictet–Spengler cyclization, the group initially speculated that the thiourea catalyst 6 interacts with the carbonyl function of the amide intermediate I and, thus, a SN2-type mechanism via hydrogen bonding catalysis was proposed. A similar bidentate carbonyl

• , right). However, based on the freshly coined concept of anion-binding activation [30][31] and as the exact interaction mode of the catalyst remained elusive, Jacobsen’s group focused their attention towards mechanistic studies of thiourea-catalyzed reactions. In 2007, they reported a Pictet–Spengler

• cyclization reaction of succinimide and glutarimide-derived hydroxylactams 7 (Scheme 3) [33]. This system was designed in a way that key experimental observations could be made to analyze whether a SN1 or SN2-type mechanism takes place. A strong dependence of the enantioselectivity on the counterion and

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• cycloisomerization/Pictet–Spengler cyclization of 2-(4-aminobut-1-yn-1-yl)aniline [16], the Ru and Rh-catalyzed [2 + 2 + 2] cycloadditions of yne-ynamides [17], and the Pd-catalyzed tandem coupling-cyclization [18] are significant works in the area (Scheme 1). However, the use of toxic and expensive metal catalysts

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• involved the synthesis of precursor (+)-198 from phenylacetic acid and (−)-α-PEA via sequential amidation, reduction and Pictet–Spengler cyclization reactions. The key anodic oxidation in the presence of NaCN converted (+)-198 to α-amino nitrile (+)-199 with excellent diastereoselectivity. Upon further

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• -triphenylporphyrin. The reaction of this porphyrin with 2,5-dimethoxytetrahydrofuran, followed by the reduction of the nitro group in the presence of NiCl2/NaBH4 afforded 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin. This triphenylporphyrin underwent a Pictet–Spengler cyclization after the reaction

• synthesis of novel meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins (4a–h) began via the Pictet–Spengler cyclization reaction [50][51] of 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (3) with various aromatic aldehydes by using 2% TFA in dichloromethane as an acidic catalyst at 0 °C for

• % yields via TFA-catalyzed Pictet–Spengler cyclization with aromatic aldehydes followed by in situ oxidation in the presence of KMnO4. These porphyrin architectures may be useful as potential candidates for various biological evaluations. (a) Electronic absorption spectra of free-base porphyrins 4f, 4g, 4h

Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1-carboxylate: Concise synthesis of alangiobussinine

• Jessica Baiget,
• Sabin Llona-Minguez,
• Stuart Lang,
• Simon P. MacKay,
• Colin J. Suckling and
• Oliver B. Sutcliffe

Beilstein J. Org. Chem. 2011, 7, 1407–1411, doi:10.3762/bjoc.7.164

• glycolate (1) to manganese dioxide would result in the formation of aldehyde 2. This can then undergo a condensation process with tryptamine (3) allowing the generation of imine 4. This intermediate is set up appropriately to undergo a Pictet–Spengler cyclization reaction resulting in the formation of

• reaction mixture. We were also unable to detect any of the nonaromatic intermediate 5, leading us to speculate that the Pictet–Spengler cyclization step, involving conversion of imine 4 to tetrahydrocarboline 5, is the step with the greatest activation energy in the process. In an attempt to lower this

• reaction. This shows that while the use of Lewis acid additives is likely to help with the Pictet–Spengler cyclization step, it may inhibit other steps in the process, e.g., by forming a strong complex with methyl glycolate (1) and therefore stopping the manganese dioxide mediated oxidation step. This

A short synthesis of (±)-cherylline dimethyl ether

• Bhima Y. Kale,
• Ananta D. Shinde,
• Swapnil S. Sonar,
• Bapurao B. Shingate,
• Sanjeev Kumar,
• Samir Ghosh,
• Soodamani Venugopal and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2009, 5, No. 80, doi:10.3762/bjoc.5.80

• followed by Pictet–Spengler cyclization. Keywords: Curtius rearrangement; Michael reaction; Pictet–Spengler cyclization; radical azidonation; Introduction Aryl-1,2,3,4-tetrahydroisoquinolines have attracted much attention from the synthetic community owing to the potential biological activities of this

• are Michael addition, radical azidonation of aldehydes [18], Curtius rearrangement, and reduction of an isocyanate intermediate followed by Pictet–Spengler cyclization. Results and Discussion Our retrosynthetic analysis of (±)-cherylline dimethyl ether (5) is depicted in Scheme 1. It can be