Polycyclic heteroaromatic hydrocarbons (hetero-PAHs) are of considerable importance in the field of medicinal chemistry (e.g., cancerostatic activity) and of materials science (e.g., for OLED or semiconductor applications). Palladium-catalyzed cross-coupling and cyclization reactions allow for a convenient and selective synthesis of a great variety of hetero-PAHs. The projects are driven both by the development of new reactions and by the synthesis of new target molecules and their properties.

Abstract: The combination of Pd-catalyzed cross-coupling with CH-arylation reactions allow for the synthesis of various hetero-PAHs with interesting optical, electronic or pharmacological properties. Simple nitro-substituted heterocycles undergo Pd-catalyzed CH-arylation reactions with excellent regioselectivity.

Review: Synlett 2024, 35, 1844–1860, DOI: 10.1055/s-0042-1751540.

Period of investigation: 2011 - Today

Keywords: Pd catalysis; heterocycles

Abstract: The combination of Pd-catalyzed C-C Cross-coupling with alkyne-carbonyl-metathesis (ACM) reactions allows for the synthesis of a variety of benzoyl-substituted hetero-PAHs.

Review: Synlett 2024, 35, 1965–1975, DOI: 10.1055/s-0042-1751513.

Period of investigation: 2016 - Today

Keywords: alkyne-carbonyl-metathesis; Pd-catalysis; heterocycles

Abstract: The combination of Pd-catalyzed C-C Cross-coupling with cycloisomerization reactions allows for the synthesis of a variety of various hetero-PAHs with interesting optical, electronic or pharmacological properties.

Review: Synlett 2022, 33, 1707–1715.

Period of investigation: 2016 - Today

Keywords: Pd-catalysis; heterocycles

Abstract: The combination of Pd-catalyzed C-C Cross-coupling with hydroamination reactions of alkynes allows for the synthesis of a variety of various polycyclic aromatic heterocycles with interesting optical, electronic or pharmacological properties.

Review: Synlett 2022, 33, 1596-1606.

Period of investigation: 2010 - Today

Keywords: Pd-catalysis; heterocycles

Abstract: The combination of Pd-catalyzed C-C Cross-coupling with twofold C-N coupling reactions allows for the synthesis of a variety of various hetero-PAHs with interesting optical, electronic or pharmacological properties.

Review: Synlett 2022, 33, 1215-1226.

Period of investigation: 2012 - Today

Keywords: Pd-catalysis; heterocycles

Abstract: Regioselective cross-coupling reactions of polyhalogenated heterocycles provide a convenient access to various arylated compounds. The regioselectivity is controlled by electronic and / or steric parameters.

Review: Synlett 2022, 33, 1029-1051.

Period of investigation: 2005 - Today

Keywords: Pd-catalysis; heterocycles

Abstract: Regioselective cross-coupling reactions of bis(triflates) provide a convenient access to various arylated compounds. The regioselectivity is controlled by electronic and / or steric parameters.

Review: Synlett 2013, 24, 412-423.

Period of investigation: 2009 - 2012

Keywords: Pd-catalysis; arenes; heterocycles

Abstract: Regioselective cross-coupling reactions of fluorohalobenzenes provide a convenient access to various arylated compounds. The regioselectivity is controlled by electronic and / or steric parameters.

Review: Synlett 2021, 32, 1784–1795.

Period of investigation: 2009 - 2013

Keywords: organofluorine chemistry; Pd-catalysis; arenes

Purines and deazapurines constitute an important class of natural products and drugs. The cyclization of heterocyclic enamines with electrophiles allows for the synthesis of a variety of drug-like compounds and natural product analogues, such as novel fluorine-substituted purines and deazapurines.

Abstract: Cyclization reactions of heterocyclic enamines with 1,3-dielectrophiles, such as 1,3-diketones, enaminones or 3-chloro-2-en-1-ones, provide access to a variety of pharmacologically relevant fluorinated purine analogues. Purines were prepared also by inverse electron-demand Diels-Alder reactions of heterocyclic enamines with triazines. Amidino-C-glycosides in their reactions with 1,3-dielectrophiles afforded pyrimidine-C-glycosides.

Review: Synlett 2022, 33, 440-457.

Period of investigation: 2009 - Today

Keywords: heterocyclic enamines; cyclizations; heterocycles

Abstract: Domino reactions of heterocyclic enamines with chromone derivatives provide a convenient access to a great variety of annulated heterocyclic ring systems. The course of the reaction depends on the type of substituent located at position 3 of the chromone.

Review: Synlett 2022, 33, 207–223.

Period of investigation: 2009 - Today

Keywords: heterocyclic enamines; cyclizations; heterocycles; chromones

Abstract: Cyclization reactions of nitro-substituted electrophilic building blocks with various nucleophiles allow for the synthesis of various nitro-substituted carbo- and heterocycles. The electron-withdrawing nitro group can be easily transformed to an electron-donating amino group which is not only pharmacologically relevant, but can also act as a nucleophile in inter- and intramolecular reactions with electrophiles, such as aldehydes, and can also be converted to other functional groups. The nitro group has the capacity to activate compounds for regioselective palladium catalyzed CH-arylation reactions. Inter- and intramolecular CH-arylations of nitro-substituted heterocyclic building blocks, such as 4-nitropyrazoles, 4-nitroimidazoles, 2-nitroindole and nitro-substituted purine analogues, allow for a convenient diversity-oriented approach to the corresponding arylated products. In addition, the nitro group can act as a leaving group in S_NAr reactions.

Review: Synlett 2024, 35, 2063–2083 (account), DOI: 10.1055/s-00000083.

Period of investigation: 2007 - 2019

Keywords: nitro compounds; cyclizations; heterocycles; silyl enol ethers; heterocyclic enamines

Abstract: A variety of domino and multicomponent reactions were developed which include domino Knoevenagel / hetero-Diels-Alder reactions, the combination of Knoevenagel reactions with [3+2] cycloadditions of nitrogen ylides, domino Knoevenagel / enamine cyclization reactions, formal [3+3] cyclizations of pyridinium salts, [3+3] cyclizations of thioxindoles with fluoroaroyl chlorides, cyclizations of heterocyclic enamines with diimines and triazines, domino [4+2] / retro [4+2] reactions, formal [3+3] cyclizations of 2-ethynylpyridines with enones, reaction of trifluoromethyl-substituted 1,3-diketones with lithiated alkynes and formal [3+2] cyclizations of 2,3-dihalopyridines with imines. These reactions provide a convenient access to various drug-like compounds.

Review: Peter Langer, Eur. J. Org. Chem. 2024, 27, e202400153 (account).

Period of investigation: 2009 - Today

Keywords: domino reactions; cyclizations; iminium salts

Abstract: N-Glycosides of indigo, indirubine and isoindigo, which can be regarded as blue, red and yellow sugars, were prepared. They show a considerable activity against various human cancer cell lines such as, for example, melanoma.

Reviews: ChemMedChem 2011, 6, 25-37.

Period of investigation: 2004 - Today

Keywords: heterocycles; carbohydrates; N-Glycosides

Abstract: A variety of domino and multicomponent reactions were developed which include domino Knoevenagel / hetero-Diels-Alder reactions, the combination of Knoevenagel reactions with [3+2] cycloadditions of nitrogen ylides, domino Knoevenagel / enamine cyclization reactions, formal [3+3] cyclizations of pyridinium salts, [3+3] cyclizations of thioxindoles with fluoroaroyl chlorides, cyclizations of heterocyclic enamines with diimines and triazines, domino [4+2] / retro [4+2] reactions, formal [3+3] cyclizations of 2-ethynylpyridines with enones, reaction of trifluoromethyl-substituted 1,3-diketones with lithiated alkynes and formal [3+2] cyclizations of 2,3-dihalopyridines with imines. These reactions provide a convenient access to various drug-like compounds.

Review: Peter Langer, Eur. J. Org. Chem. 2024, 27, e202400153 (account).

Period of investigation: 2009 - Today

Keywords: domino reactions; cyclizations; iminium salts

Abstract: Domino reactions of heterocyclic enamines with chromone derivatives provide a convenient access to a great variety of annulated heterocyclic ring systems. The course of the reaction depends on the type of substituent located at position 3 of the chromone.

Review: Synlett 2022, 33, 207–223.

Period of investigation: 2009 - Today

Keywords: heterocyclic enamines; cyclizations; heterocycles; chromones

Abstract: Domino reactions of chromones with activated carbonyl compounds, such as dimethyl acetone-1,3-dicarboxylate and 1,3-diphenylacetone, and with 1,3-bis(silyloxy)-1,3-butadienes, electroneutral equivalents of 1,3-dicarbonyl dianions, allow for a convenient synthesis of a great variety of products. The regioselectivity and course of the reaction depends on the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed.

Review: Peter Langer, Beilstein J. Org. Chem. 2024, 20, 1256-1269.

Period of investigation: 2002 - Today

Keywords: domino reactions; chromones; 1,3-dicarbonyl compounds

Abstract: 4-(Silyloxy)benzopyrylium triflates can be readily generated in situ by reaction of chromones with trialkylsilyl-trifluoromethanesulfonate. Domino reactions of bis(silyl enol ethers) with such benzopyrylium triflates – derived from chromones, 3-cyanochromones and 3-formylchromones – allow for an efficient synthesis of a variety of carbo- and heterocycles.

Review: Synlett 2007, 1016-1025.

Period of investigation: 2001 - 2011

Keywords: silyl enol ethers; chromones; heterocycles

Abstract: The combination of Heck reactions with 6p-electrocyclization reactions allows for the synthesis of a variety of various benzoannulated heterocycles.

Review: Synlett 2012, 23, 2735-2745.

Period of investigation: 2008 - 2013

Keywords: Pd-catalysis; heterocycles; domino reactions

Abstract: 2-Isothiocyanatobenzonitrile (ITCB) and isocyanatobenzonitrile (ICB) represent versatile synthetic building blocks containing a nitrile and an isothiocyanate or an isocyanate function, respectively. Domino reactions of ITCB and ICB provide a convenient access to a variety of pharmacologically important heterocycles.

Review: Curr. Org. Chem. 2009, 13, 955-964.

Period of investigation: 2002 – 2009

Keywords: domino reactions; cyclizations; heterocycles

Abstract: 2-Isothiocyanatobenzonitrile (ITCB) and isocyanatobenzonitrile (ICB) represent versatile synthetic building blocks containing a nitrile and an isothiocyanate or an isocyanate function, respectively. Domino reactions of ITCB and ICB provide a convenient access to a variety of pharmacologically important heterocycles.

Review: Curr. Org. Chem. 2009, 13, 955-964.

Period of investigation: 2002 – 2009

Keywords: domino reactions; cyclizations; heterocycles

Abstract: The cyclization of 1,1-diacylcyclopropanes with free and masked dianions provides spirocyclopropanes which readily undergo ring-cleavage reactions. Cyclopropylated 1,3,5-tricarbonyl compounds were prepared for the first time. Based on this work also other syntheses of cyclopropanes were developed.

Review: Synlett 2023, 34, 1765-1776.

Period of investigation: 2002 - 2011

Keywords: cyclopropanes; cyclizations; dianions; 1,3-dicarbonyl compounds

Abstract: The cyclization of oxaldiimidoyl dichlorides, readily available novel building blocks, with ambident dianions and other bis(nucleophiles), such as diamines, provides a convenient access to a variety of heterocycles important in medicinal chemistry or materials science. Reactions include cyclization-, domino-, one-pot- and double-anion-capture-reactions.

Review: Eur. J. Org. Chem. 2002, 221-234.

Period of investigation: 1999 – 2006

Keywords: cyclizations; dianions; heterocycles

Abstract: (2,4-Dioxobutylidene)phosphoranes can be regarded as equivalents of 1,3-dicarbonyl dianions and represent versatile building blocks in one-pot cyclizations. Their reactions with various electrophiles, such as 1,3-dicarbonyl compounds, enones, a-halo ketones, or hydrazine derivatives, allow for a convenient synthesis of a variety of carbo- and heterocyclic ring systems.

Review: Synthesis 2008, 3877-3902.

Period of investigation: 2000 – 2007

Keywords: 1,3-dicarbonyl compounds; cyclizations; heterocycles; arenes

Abstract: Domino reactions of heterocyclic enamines with chromone derivatives provide a convenient access to a great variety of annulated heterocyclic ring systems. The course of the reaction depends on the type of substituent located at position 3 of the chromone.

Review: Synlett 2022, 33, 207–223.

Period of investigation: 2009 - Today

Keywords: heterocyclic enamines; cyclizations; heterocycles; chromones

Abstract: Domino reactions of chromones with activated carbonyl compounds, such as dimethyl acetone-1,3-dicarboxylate and 1,3-diphenylacetone, and with 1,3-bis(silyloxy)-1,3-butadienes, electroneutral equivalents of 1,3-dicarbonyl dianions, allow for a convenient synthesis of a great variety of products. The regioselectivity and course of the reaction depends on the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed.

Review: Peter Langer, Beilstein J. Org. Chem. 2024, 20, 1256-1269.

Period of investigation: 2002 - Today

Keywords: domino reactions; chromones; 1,3-dicarbonyl compounds

Abstract: 4-(Silyloxy)benzopyrylium triflates can be readily generated in situ by reaction of chromones with trialkylsilyl-trifluoromethanesulfonate. Domino reactions of bis(silyl enol ethers) with such benzopyrylium triflates – derived from chromones, 3-cyanochromones and 3-formylchromones – allow for an efficient synthesis of a variety of carbo- and heterocycles.

Review: Synlett 2007, 1016-1025.

Period of investigation: 2001 - 2011

Keywords: silyl enol ethers; chromones; heterocycles

Abstract: Benzo[c]coumarins and related fused coumarins were prepared by cyclization of various nucleophiles with 4-chlorocoumarins and by related syntheses. Suzuki-Miyaura reactions of coumarin-derived bis(triflates) result in formation of arylated coumarins with excellent regioselectivity which is controlled by electronic and steric features of the substrate.

Review: Synlett 2024, DOI: 10.1055/s-0042-1751556.

Period of investigation: 2001 - Today

Keywords: heterocycles; heterocyclic enamines; cyclizations; silyl enol ethers

Abstract:A variety of 1,3-selenazoles and related compounds, including 2,4,5-trisubstituted, 2,4-disubstituted, 4,5-disubstituted, 4-substituted 1,3-selenazoles and parent unsubstituted 1,3-selenazole and 1,3,4-6H-selenadiazines, were prepared. Most syntheses rely on the application of selenocarboxylic amides, selenourea and related building blocks which are conveniently available by reaction of the corresponding oxygen analogues with P₄Se₁₀. 1,3-Selenazoles are of pharmacological relevance.

Review: Synlett 2022, 33, 728-736.

Period of investigation: 2002 - 2015

Keywords: heterocycles; cyclizations

Dianions are twofold deprotonated organic compounds. They can be used as building blocks for the synthesis of a variety of carbo- and heterocyclic products which are of pharmacological relevance.

Abstract: 2-(Alkylidene)tetrahydrofurans are prepared by cyclization of 1,3-dicarbonyl dianions or 1,3-bis(silyloxy)-1,3-butadienes with various electrophiles. The products represent versatile building blocks for hydrogenation, cross-coupling, bromination and oxidation reactions.

Reviews: Tetrahedron 2007, 63, 10865-10888; Chem. Rev. 2004, 104, 4125-4149.

Period of investigation: 1999 – 2007

Keywords: 1,3-dicarbonyl compounds; dianions; silyl enol ether; cyclizations; heterocycles

Abstract: Cyclization reactions of epichlorohydrin and epibromohydrin with free and masked dianions allow for a convenient synthesis of a variety of products, such as 2-(alkylidene)tetrahydrofurans, which can be further funcionalized by hydrogenation or ring transformation reactions, cyclopropanes, γ-butyrolactams, oxazines, oxazolo[3,4-b]pyridazin-7-ones or 2-(alkylidene)thiazolidines. In general, the reactions proceed with very good regioselectivity.

Review: Synlett 2023, 34, 1953-1960.

Period of investigation: 1999 - 2006

Keywords: dianions; 1,3-dicarbonyl compounds; cyclizations; silyl enol ethers

Abstract: One-pot cyclizations of oxime and hydrazone dianions with various electrophiles provide an efficient synthesis of functionalized isoxazoles, pyrazoles and other heterocycles.

Review: Synlett 2011, 2633-2342.

Period of investigation: 2005 - 2015

Keywords: dianions; cyclizations; heterocycles

Abstract: Cyclizations of the dianion of 1,1-diphenylacetone allows for the synthesis of various heterocycles. From a study directed towards the regioselectivity of such reactions a new allene synthesis via allene dianions was found by serendipity. Reactions of allene dianions with various electrophiles were studied.

Review: Synlett 2023, 34, 414–422.

Period of investigation: 1993 - 2003

Keywords: allenes; cyclizations; dianions

Abstract: The cyclization of oxaldiimidoyl dichlorides, readily available novel building blocks, with ambident dianions and other bis(nucleophiles), such as diamines, provides a convenient access to a variety of heterocycles important in medicinal chemistry or materials science. Reactions include cyclization-, domino-, one-pot- and double-anion-capture-reactions.

Review: Eur. J. Org. Chem. 2002, 221-234.

Period of investigation: 1999 – 2006

Keywords: cyclizations; dianions; heterocycles

1,3-Bis(silyloxy)-1,3-butadienes represent electroneutral equivalents of 1,3-dicarbonyl dianions. 1,1-Bis(silyloxy)ketene acetals can be regarded as masked carboxylic dianions. 1,3-bis(trimethylsilyloxy)alk-1-enes represent equivalents of dianions of β-hydroxyesters. All these building blocks undergo Lewis acid-mediated cyclization reactions with a variety of electrophiles.

Abstract: A variety of butenolides were prepared by cyclization of bis(silyl enol ethers), such as 1,3-bis(silyloxy)-1,3-butadienes, 1,3-bis(trimethylsilyloxy)alk-1-enes or 1,1-bis(silyloxy)ketene acetals, with oxalyl chloride. The products are of pharmacological relevance.

Review: Synlett 2006, 3369-3381.

Period of investigation: 1999 – 2009

Keywords: silyl enol ethers; cyclizations; heterocycles

Abstract: 4-(Silyloxy)benzopyrylium triflates can be readily generated in situ by reaction of chromones with trialkylsilyl-trifluoromethanesulfonate. Domino reactions of bis(silyl enol ethers) with such benzopyrylium triflates – derived from chromones, 3-cyanochromones and 3-formylchromones – allow for an efficient synthesis of a variety of carbo- and heterocycles.

Review: Synlett 2007, 1016-1025.

Period of investigation: 2001 - 2011

Keywords: silyl enol ethers; chromones; heterocycles

Abstract: The reaction of 1,3-bis(silyloxy)-1,3-butadienes with funcionalized and non-funcionalized acid chlorides and bis(acid chlorides) gives rise to the formation of a great variety of open-chained 1,3,5-tri- and 1,3,5,7-tetracarbonyl compounds and of cyclic products derived from them. Permethylated and cyclopropanated polycarbonyl compounds were successfully prepared by a stepwise protocol.

Review: Synlett 2021, 32, 2036-2045.

Period of investigation: 1999 - 2011

Keywords: silyl enol ethers; 1,3-dicarbonyl compounds

Abstract: 1,1-Bis(silyloxy)ketene acetals represent useful synthetic building blocks which can be regarded as masked carboxylic acid dianions. In recent years, a number of cyclization reactions of 1,1-bis(silyloxy)ketene acetals have been reported which provide a convenient synthesis of various pharmacologically relevant heterocyclic products.

Review: Synlett 2012, 23, 1283-1290.

Period of investigation: 2005 - 2008

Keywords: silyl enol ethers; heterocycles; cyclizations

Abstract: Lewis acid mediated [3+3] cyclizations of 1,3-bis(silyl enol ethers) with 1,3-dielectrophiles, such as 1,1,3,3-tetramethoxypropane, 3-silyloxy-2-en-1-ones and 1,1-diacylcyclopropanes, provide an efficient approach to a variety of functionalized arenes (such as salicylates and phenols) and other six-membered carbocyclic products which are of pharmacological relevance.

Review: Synthesis 2007, 327-347.

Period of investigation: 2002 – 2014

Keywords: silyl enol ether; cyclizations; arenes

Abstract: Formal [3+3] cyclocondensation reactions of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with functionalized and non-functionalized 1-alkyl- and 1-aryl-3-alkoxy-2-en-1-ones, 1,1-dichloro-3-buten-2-ones, 3-acyl-4,5-dihydrofurans and other related 1,3-dielectrophiles provide a convenient and regioselective approach to various highly substituted, functionalized phenols.

Review: Curr. Org. Chem. 2012, 16, 557-565.

Period of investigation: 2004 – 2014

Keywords: silyl enol ether; cyclizations; arenes

Abstract: Cyclocondensation reactions of sulfur-containing dienes, such as 3-arylthio-1-silyloxy-1,3-butadienes and 4-arylthio-1,3-bis(trimethylsilyloxy)-1,3-butadienes, with various dielectrophiles and dieneophiles allow for a convenient synthesis of a variety of functionalized and sterically encumbered aryl-substituted sulfides and sulfones.

Review: Synlett 2010, 2383-2391.

Period of investigation: 2005 - 2014

Keywords: silyl enol ethers; cyclizations; arenes

Abstract: One-pot cyclizations of fluorinated 1,3-bis(silyloxy)-1,3-butadienes and 3-alkoxy- and 3-silyloxy-2-en-1-ones provide a convenient access to various fluoro-, trifluoromethyl- and perfluoroalkyl-substituted arenes and hetarenes.

Review: Synlett 2019, 30, 665-773.

Period of investigation: 2005 - 2010

Keywords: silyl enol ethers; cyclizations; arenes; heterocycles

Abstract: Cyclization reactions of nitro-substituted electrophilic building blocks with various nucleophiles allow for the synthesis of various nitro-substituted carbo- and heterocycles. The electron-withdrawing nitro group can be easily transformed to an electron-donating amino group which is not only pharmacologically relevant, but can also act as a nucleophile in inter- and intramolecular reactions with electrophiles, such as aldehydes, and can also be converted to other functional groups. The nitro group has the capacity to activate compounds for regioselective palladium catalyzed CH-arylation reactions. Inter- and intramolecular CH-arylations of nitro-substituted heterocyclic building blocks, such as 4-nitropyrazoles, 4-nitroimidazoles, 2-nitroindole and nitro-substituted purine analogues, allow for a convenient diversity-oriented approach to the corresponding arylated products. In addition, the nitro group can act as a leaving group in S_NAr reactions.

Review: Synlett 2024, 35, 2063–2083 (account), DOI: 10.1055/s-00000083.

Period of investigation: 2007 - 2019

Keywords: nitro compounds; cyclizations; heterocycles; silyl enol ethers; heterocyclic enamines

Abstract: A variety of butenolides were prepared by cyclization of bis(silyl enol ethers), such as 1,3-bis(silyloxy)-1,3-butadienes, 1,3-bis(trimethylsilyloxy)alk-1-enes or 1,1-bis(silyloxy)ketene acetals, with oxalyl chloride. The products are of pharmacological relevance.

Review: Synlett 2006, 3369-3381.

Period of investigation: 1999 – 2009

Keywords: silyl enol ethers; cyclizations; heterocycles

Abstract: The cyclization of oxaldiimidoyl dichlorides, readily available novel building blocks, with ambident dianions and other bis(nucleophiles), such as diamines, provides a convenient access to a variety of heterocycles important in medicinal chemistry or materials science. Reactions include cyclization-, domino-, one-pot- and double-anion-capture-reactions.

Review: Eur. J. Org. Chem. 2002, 221-234.

Period of investigation: 1999 – 2006

Keywords: cyclizations; dianions; heterocycles

Abstract: The cyclization of 1,1-diacylcyclopropanes with free and masked dianions provides spirocyclopropanes which readily undergo ring-cleavage reactions. Cyclopropylated 1,3,5-tricarbonyl compounds were prepared for the first time. Based on this work also other syntheses of cyclopropanes were developed.

Review: Synlett 2023, 34, 1765-1776.

Period of investigation: 2002 - 2011

Keywords: cyclopropanes; cyclizations; dianions; 1,3-dicarbonyl compounds