Phosphine-promoted intramolecular Rauhut-Currier/Wittig reaction cascade to access (hetero)arene-fused diquinanes.

We describe the first phosphine-promoted intramolecular Rauhut-Currier reaction that triggers an intramolecular Wittig process assembling new classes of diquinanes. The one-pot strategy provides ready access to simple diquinanes and various (hetero)arene-fused diquinanes incorporated with up to two contiguous all-carbon quaternary centers under metal-free and neutral conditions. We showcased the generality of the method on a broad range of substrates and demonstrated its synthetic utility in accessing various advanced intermediates relevant to natural product synthesis and material science.

Correction: Professor (Dr) Sukh Dev: an iconic scientist with an innate sixth sense who radicalized natural product synthesis & organic chemistry.

Correction for 'Professor (Dr) Sukh Dev: an iconic scientist with an innate sixth sense who radicalized natural product synthesis & organic chemistry' by Harry Kochat et al., Org. Biomol. Chem., 2024, 22, 5466-5469, https://doi.org/10.1039/D4OB90071E.

Phosphine-catalysed denitrative rearomatising (3 + 2) annulation of α,ß-ynones and 3-nitroindoles.

We describe a metal-free strategy to access various α-arylidene cyclopenta[b]indoles via phosphine-catalysed (3 + 2) annulation of α,ß-ynones and 3-nitroindoles. For the first time, the rearomatisation of the indole nucleus was observed in such an annulative transformation. The method was extended to the synthesis of an antimalarial natural product, bruceolline E.

Hypothesis-Driven Palladium-Catalyzed Transformations for the Construction of New Molecular Architectures.

The development of new synthetic protocols to access diverse molecular scaffolds from readily available starting compounds is of significance in both academia and industry. Towards this, the catalysis by transition metals has been employed as a powerful tool to access molecules with broad structural and functional diversity. An overview of the recent literature manifested the tremendous potential of transition metal-catalyzed processes in advancing organic synthesis in a new direction. This account compiles new conceptual advancements in the palladium-catalyzed Alder-ene type cycloisomerization reactions, C-H functionalizations, and one-pot multicatalytic processes, which have become essential tools to access new classes of molecules.

Divergent Michael/Aldol Cascades Under Semi-Aqueous Conditions: Synthesis of Cyclopenta- and Cycloheptannulated (Hetero)arenes.

The synthesis of 3-acetoxyindanones and (hetero)arene-fused dihydrotropones was achieved via divergent annulation cascades. Under mild aqueous and basic conditions, α-substituted enone-aldehydes and 1,3-carbonyls undergo a Michael/aldol/hemiketalization/retro-aldol cascade for the formation of 3-acetoxyindanones possessing two contiguous stereogenic centers, one of which is an all-carbon quaternary center. On the other hand, the same enone-aldehydes generate new classes of fused-dihydrotropones upon reaction with 2,4-dioxobutanoates under merely the same reaction conditions via a Michael/aldol/lactonization/decarboxylation cascade.

Phosphine- and water-promoted pentannulative aldol reaction.

Herein, an efficient metal-free intramolecular aldol reaction for the synthesis of an unusual class of cyclopentanoids is described. The reaction of α-substituted dienones tethered with ketones in the presence of tributylphosphine and water provided aldols. The role of water was realised to be crucial for this transformation. Furthermore, isotopic labeling experiments provided vital information about the reaction mechanism.

Palladium-Catalyzed Intramolecular Trost-Oppolzer-Type Alder-Ene Reaction of Dienyl Acetates to Cyclopentadienes.

A new approach to the synthesis of highly substituted cyclopentadienes, indenes, and cyclopentene-fused heteroarenes by means of the Pd-catalyzed Trost-Oppolzer-type intramolecular Alder-ene reaction of 2,4-pentadienyl acetates is described. This unprecedented transformation combines the electrophilic features of the Tsuji-Trost reaction with the nucleophilic features of the Alder-ene reaction. The overall outcome can be perceived as a hitherto unknown "acid-free" iso-Nazarov-type cyclization. The versatility of this strategy was further demonstrated by the formal synthesis of paucifloral F, a resveratrol-based natural product.

One-Pot Multicatalytic Approaches for the Synthesis of Cyclohepta[b]indoles, Indolotropones, and Tetrahydrocarbazoles.

Diversity oriented one-pot synthesis of cyclohepta[b]indoles, indolotropones, and tetrahydrocarbazoles (THCs) have been reported. Readily accessible 3-(2-aminophenyl)-5-hexenyn-3-ols under a one-pot trimetallic orthogonal catalysis furnish tetrahydrocyclohepta[b]indoles, and a one-pot quadruple reaction sequence of the enynols generates dihydrocyclohepta[b]indoles and indolotropones. During this study, formation of THCs was realized to be a reason for the yield loss in certain cases, this observation led to the development of a one-pot bimetallic approach for the synthesis of 1,3-disubstituted THCs.

A computational investigation of the solvent-dependent enantioselective intramolecular Morita-Baylis-Hillman reaction of enones.

The intramolecular Morita-Baylis-Hillman reaction of ß-mono and ß,ß-disubstituted enones shows high yields and stereo-selective products when the reaction is performed in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a solvent. In this work, we carried out a computational study using the density functional Becke 3-(B3) parameter exchange and the Lee-Yang-Parr (LYP) correlation functional and 6-31+G* basis set. Two major steps i.e. C-C bond formation and proton transfer were analysed using different pathways. The calculations show a very low barrier (ΔG† = 0.23 kcal mol-1) for C-C bond formation in the case of an experimentally dominant product. For this pathway the subsequent proton transfer via the HFIP step has a barrier of 26.98 kcal mol-1. The same has been confirmed using a Molecular Electrostatic Potential (MESP), which shows a negative region in between CC in the transition state. In spite of high barriers for proton transfer, the intermediate products formed in this reaction pathway are thermodynamically more stable in comparison with other pathways. The thermodynamic stability of the final product in this pathway is observed to surpass all other effects in the presence of HFIP, thereby corroborating the experimentally observed enantioselectivity.

Cyclopenta[b]annulation of Heteroarenes by Organocatalytic γ'[C(sp3 )-H] Functionalization of Ynones.

A new approach for the cyclopenta[b]annulation of heteroarenes through metal-free and directing-group-free γ'[C(sp3 )-H] functionalization and intramolecular hydroalkylation of ynones has been developed. In an unprecedented event, nucleophilic addition of an organophosphine to the designed ynones triggers γ'[C(sp3 )-H] functionalization, leading to the formation of heteroaryl-based ortho-quinodimethane (oQDM) intermediates that undergo carbocyclization to provide cyclopentannulated heteroarenes in good yields and excellent stereoselectivities. Deuterium-labeling experiments substantiated the proposed reaction mechanism as well as the speculated epimerization.

One-pot relay catalysis: divergent synthesis of furo[3,4-b]indoles and cyclopenta[b]indoles from 3-(2-aminophenyl)-1,4-enynols.

Described herein is an efficient divergent strategy for the synthesis of furo[3,4-b]indoles via a sequential Ag(i)/Bi(iii)/Pd(ii) catalysis and cyclopenta[b]indoles via a one-pot Ag(i)/Brønsted acid relay catalysis from 3-(2-aminophenyl)-4-pentenyn-3-ols, accessible in three simple steps from 2-aminobenzaldehydes.

Morita-Baylis-Hillman Reaction of ß,ß-Disubstituted Enones: An Enantioselective Organocatalytic Approach for the Synthesis of Cyclopenta[b]annulated Arenes and Heteroarenes.

The first enantioselective organocatalytic intramolecular Morita-Baylis-Hillman (MBH) reaction of sterically highly demanding ß,ß-disubstituted enones is presented. The MBH reaction of ß,ß-disubstituted-α,ß-unsaturated electron-withdrawing systems was previously considered to be unfeasible. Towards this end, designer substrates, which under simple and practical reaction conditions generate a variety of cyclopenta[b]annulated arenes and heteroarenes in excellent enantiopurities and near-quantitative yields in remarkably short reaction times, are described. The reason for the unusually facile nature of this reaction is attributed to the synergy guided and entropically favored intramolecular reaction. Further, this strategy provides easy access to a substantial number of bioactive natural products and pharmaceutically significant compounds.

One-Pot Trimetallic Relay Catalysis: A Unified Approach for the Synthesis of ß-Carbolines and Other [c]-Fused Pyridines.

A divergent strategy is presented for the synthesis of 1,3-di- and 1,3,4-trisubstituted ß-carbolines through an unprecedented one-pot triple-orthogonal-metal relay catalysis, and 1,3-disubstituted 4-hydroxy-ß-carbolines through a one-pot bimetallic relay catalysis from readily accessible 3-(2-aminophenyl)-5-hexenyn-3-ols. These strategies were elaborated to enable the synthesis of benzofuro[2,3-c]pyridines, benzothieno[2,3-c]pyridines, and isoquinolines, which otherwise require multistep synthesis.

Modular assembly of furotropones and benzofurotropones, and study of their physicochemical properties.

A rapid and straightforward synthesis of a novel series of furo[2,3-d]tropones (or cyclohepta[b]furan-6-ones) has been developed starting from readily and commercially available materials. Directed α-lithiation of furan-3-carboxaldehydes and subsequent reaction with a variety of aldehydes efficiently provide, in one step, access to 3-formyl-2-furylcarbinols, which are otherwise only accessible with difficulty. The 3-formyl-2-furylcarbinols are further elaborated in two steps to the synthesis of furo[2,3-d]tropones in good yields via sequential bismuth(III)chloride-catalyzed furfurylation and an unusual base promoted cyclization strategy. Thus, diverse polysubstituted furotropones and benzofurotropones can be rapidly assembled. This methodology thereby offers a potential approach for the synthesis of several bioactive natural products containing cyclohepta[b]furan core and also for the buildup of complex molecular architectures through higher order cycloaddition reactions of tropones. Further, the new chromophores have been found to possess promising fluorescence properties. Selective fluorogenic sensing behavior of furotropones toward Fe(3+) ions has also been elucidated.

Interrupted Corey-Chaykovsky Reaction of Tethered Bis-Enones to Access 2,3-Epoxy-hexahydrofluoren-9-ones.

The Corey-Chaykovsky reaction is usually employed to synthesize cyclopropanes from activated olefins. We intercepted the intermediates prevailing during this transformation and diverted the process for the creation of intricate molecular motifs. We describe an unusual skeletal remodelling of tethered bis-enones to 2,3-epoxy-hexahydrofluoren-9-ones via an "interrupted Corey-Chaykovsky reaction". The strategy rationally merges the nucleophilic features of sulfur ylides with electronically biased olefins to achieve the regio- and stereoselective synthesis of several new classes of hydrofluorenones. We have demonstrated the synthetic utility of the products in accessing several highly functionalized molecules.

Phosphine-Promoted Ring Opening/Recyclization of Cyclopropyl Ketones to Access Hydrofluorenones.

The ring-reorganizing transformations of activated cyclopropanes are typically achieved under acidic conditions. This Letter describes the first acid-free and Lewis base-mediated cascade ring opening/recyclization of designed cyclopropyl ketones to access tetrahydrofluorenones. We rationally merged the nucleophilic features of phosphines with the electronically biased cyclopropanes to synthesize several new classes of hydrofluorenones. We have also demonstrated the synthetic utility of the products in accessing highly functionalized molecular scaffolds.

A one-pot telescopic synthesis of benzo[b]carbazoles and exploration of their liquid crystalline properties.

We describe a diversity-oriented one-pot telescopic synthesis of various benzo[b]carbazoles with the naphthannulation of indoles as the key step, enabled by an intramolecular furan-olefin Diels-Alder reaction. This strategy is general and efficient across a wide range of substrates. We applied this method to synthesize and characterize the first benzo[b]carbazole-based liquid crystalline materials, where the unique molecular design led to the formation of a rare nematic phase at room temperature.

Morita-Baylis-Hillman Spirannulation under Phosphine- and Anion-Binding Catalysis.

We introduce an advancement in Morita-Baylis-Hillman (MBH) chemistry that provides access to α-spirannulated enones. The treatment of enone-tethered azaarenium salts with catalytic amounts of organophosphines provides spiroindenyl dihydropyridines. It represents the α-spirannulation of enones via an intramolecular MBH (IMBH) reaction utilizing dual phosphine- and anion-binding catalysis. The IMBH adducts were subjected to several post-synthetic modifications to access highly functionalized molecules.

Spectral characteristics of the flavones and anthocyanins present in passionflower (Passiflora incarnata).

Rich in antioxidants with a variety of flavones and anthocyanins, passionflower/fruit has been extensively used in food, beverage, medicinal, and natural dyes industries. The individual components present in passionflower are identified by extracting them in methanol, partitioning them between ethyl acetate and aqueous layers, and recording their ESI mass spectrometric data. The steady-state absorption and fluorescence spectra of the extract in methanol and dimethyl sulfoxide are recorded and the lifetime of the fluorescing species is reported. The pH dependence of the absorption spectrum confirms the presence of the anthocyanins.