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

• hydrolysis of 4a was observed in most cases in trace amounts; an exception is entry 18 (Table 1), in which the 1,4-diketone 5a was isolated in 10% yield. With the optimized reaction conditions in hand, we investigated the scope of the developed tetrahydrofuro[3,2-c]pyridine synthesis. We found that a wide

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• pyridine syntheses have relied on the condensation of carbonyl compounds and amines for a very long time [11]. The classical methods for the synthesis of functionalized pyridine include the Hantzsch pyridine synthesis and the Bohlmann–Rahtz synthesis (Scheme 1a and b). Furthermore, alternative

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• of ammonia, formaldehyde, and acetaldehyde; and iii) preparation from furfural and ammonia. In addition, Hantzsch pyridine synthesis from ethyl acetoacetate, formaldehyde, and ammonia is a commonly used laboratory synthetic method. Recently, extensive and efficient methods for the construction of

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• Guareschi pyridine synthesis is a modified two-component version, mechanistically similar to the Biginelli pyrimidine synthesis [33] and based on the condensation of cyanoacetamide and a β-dicarbonyl derivative [45][46]. This is the most famous Guareschi pyridine synthesis, both in textbooks and in other

• reaction reported in 1898 [50]. It involves the reaction of a β-dicarbonyl (ester or diketone) with a primary amine or ammonia and a cyanoacetic ester. The mechanism of this condensation closely resembles the three-component version of the Hantzsch pyridine synthesis and generates 6-hydroxypyridones. Also

• mechanistically similar to the Hantzsch pyridine synthesis is the Guareschi type-IV pyridine synthesis, first reported in 1897 [7] and involving the four-component condensation of ammonia, a carbonyl derivative, and two molecules of a cyanoacetic ester. The reaction affords 3,5-dicyanoglutarimides, known as

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• 61 in a one-pot fashion, by reacting 2-AP 3 and 1,3-diphenylprop-2-yn-1-one 60 under the given conditions. This one-pot methodology provided the final product with a yield of 50% (Scheme 21). For pyridine synthesis, both N-pyridyl as well as enone fragment have well tolerated a large number of

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• with trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a tertiary amine as base a broad range of pyridine derivatives was accessible (Scheme 3). According to its discoverer, we named this reaction Flögel pyridine synthesis [21]. The reaction is very flexible with respect to the employed

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• contributions have been made by synthetic chemists to search for new method for the efficient synthesis and functionalization of pyridines. Among the most significant techniques are condensation reactions between reactive carbonyls and amines (namely Hantzsch [10] and Chichibabin pyridine synthesis [11][12

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• we reported on a new pyridine synthesis starting from symmetrically substituted 1,3-diketones 1a and 1b, respectively, that were converted into the corresponding β-ketoenamines and subsequently by N-acylation into β-ketoenamides such as 3a or 3b [1]. Their cyclocondensation followed by O-alkylation

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• to the β-position of the conjugated olefin followed by nucleophilic attack of the enamine. Use of a Chan–Lam reaction for the synthesis of tetrahydroquinolines and potential extension to pyridines [8]. Examples of pyridine synthesis from oxime precursors [51][52]. Solvent effect on conversion of N

The simple production of nonsymmetric quaterpyridines through Kröhnke pyridine synthesis

• Isabelle Sasaki,
• Jean-Claude Daran and
• Gérard Commenges

Beilstein J. Org. Chem. 2015, 11, 1781–1785, doi:10.3762/bjoc.11.193

• -2,2’:6’,2’’-terpyridine through a Kröhnke pyridine synthesis. Easy access to 6-acetyl-2,2’:6’,2’’-terpyridine starting from 2,6-diacetylpyridine and 2-acetylpyridine is described. The X-ray analysis of a chiral quaterpyridine and its Pt(II) complex is presented. Keywords: heterocycles; Kröhnke

• pyridine synthesis; Mannich bases; platinum; X-ray diffraction; Findings Polypyridines have been demonstrated to be useful building blocks in metallo-supramolecular chemistry [1][2][3]. In particular, polypyridines joined at the 2,6-position have the ability to accommodate different coordination numbers

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• (3.6 mL), rt, 20 min. Iodination of aryldiazonium tetrafluoroborates 3. Reaction conditions: 3 (1 mmol), I2 (1.1 mmol), pyridine (4 mmol), MeCN (3 mL), 2 h. aYields in the presence of collidine instead of pyridine. Synthesis of boronates 2 from aniline derivatives 1a. Synthesis of diazonium

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• cyclopropane derivatives 30 (62%) and 32 (44%). Later, Michael addition in the presence of caesium fluoride and benzyltriethylammonium chloride in DMF gave the benzannulated cyclodecanone derivatives 31 (11%) and 33 (10%) (Scheme 2). Oxymercuration – Hantzsch pyridine synthesis: Kondo and Miyake [86] have

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• pyridine structural class. Pyridine itself is produced industrially by either the traditional Chichibabin pyridine synthesis (Scheme 1, A), the Bönnemann reaction, a cobalt-catalysed cyclotrimerisation of alkynes and nitriles (Scheme 1, B) or the aerobic gas-phase condensation of croton aldehyde

• substituted 2-pyridones (Scheme 9) [34][35]. This protocol is closely related to the Hantzsch pyridine synthesis and offers access to a wide range of products with well-defined regioselectivity. The simple undecorated parent 2-pyridone (1.42) can be somewhat harder to access but is obtained in a linear

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• Microwave Technology Ltd, 2 Middle Slade, Buckingham, MK18 1WA, UK 10.3762/bjoc.9.232 Abstract The Bohlmann–Rahtz pyridine synthesis and the Hantzsch dihydropyridine synthesis can be carried out in a microwave flow reactor or using a conductive heating flow platform for the continuous processing of

• dihydropyridine synthesis; heterocycles; microwave synthesis; multicomponent reactions; pyridine synthesis; Introduction Microwave-assisted synthesis has revolutionized many processes in recent years as a valuable alternative to the use of conductive heating for accelerating transformations in synthetic organic

• materials could be realized. Introduction to the Bohlmann–Rahtz pyridine synthesis Bohlmann and Rahtz first reported the synthesis of trisubstituted pyridines from a stabilized enamine, such as ethyl β-aminocrotonate (11), and an ethynyl carbonyl compound, such as butynone (12a), in 1957 [49]. In its

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• group on the nitrogen may allow such a selective process and a clean formation of the (dihydro)pyridine ring system. We have indeed demonstrated the efficiency of this strategy [40] and now report in this manuscript a full account on this work as well as the application of our pyridine synthesis to a

• , which does confirm that our deprotonation/carbometallation sequence is not suitable for the preparation of C-2-substituted (1,4-dihydro)pyridines. Application to a formal synthesis of sarizotan To further probe the synthetic utility of our pyridine synthesis, we next envisioned its use for the synthesis

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• nucleophilic substitution reactions. Conclusion We have demonstrated that enantiopure functionalized carboxylic acids and nitriles can be used without problems in our previously reported pyridine synthesis. The starting materials were successfully transformed into the corresponding pyridines without loss of

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• analogue 120 using acetic anhydride in pyridine. Synthesis of arylderivatives The synthesis of 5-[alkoxy-(4-nitrophenyl)methyl]uracils 124 (Scheme 21) has recently been investigated [34]. The authors reported the synthesis of alkoxy derivatives with alkyl chain lengths C1-C12 whose preparation started with