Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

• -catalyzed hydrophosphinylation [45]. The key heterocyclization of 11 into 12 was accomplished using silver-promoted homolytic aromatic substitution [46], which was superior to our own manganese methodology (43% yield) [36]. Copper-catalyzed arylation [34] of 12 with iodobenzene and 4-nitroiodobenzene gave

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• ordering between the 3CT and 3LE states in NI-PTZ and NI-PTZ-O. The tuning of the energy order of the 3CT and 3LE state is achieved by the feasible oxidation of the PTZ unit in the dyads, while the other factors kept intact; this approach may become a promising methodology in the study of the entangled

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• dehydrogenase (GMD). We first synthesise C6-modified glycosyl 1-phosphates, incorporating 6-amino, 6-chloro and 6-sulfhydryl groups, followed by their evaluation as substrates for enzymatic pyrophosphorylative coupling. The development of this methodology enables access to GDP 6-chloro-6-deoxy-ᴅ-mannose and its

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• , which was named as 2-phosphaindolizine perceiving it to result from a formal CH/P exchange at the 2-position of indolizine (2) (Figure 1) [1]. Subsequently a good library of these interesting compounds became accessible [1]. The methodology could be extended successfully to the synthesis of 1,3,4

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• compatible means in the view of a one-pot methodology for preparing isocyanides directly from amines [56]. When the amine 1 was reacted in the presence of Et3N, HCOOH, and p-Ts-Im [58] (Table 1, entry 5), the formamide was accompanied by a significant amount of sulfonamide (formamide/sulfonamide ratio: 70:30

• hand, the methodology was successfully applied to the synthesis of several formamides starting from a series of aromatic amines (Scheme 1). The N-formyl derivative 3 was prepared in good yields as well as formanilides bearing halogen substituents, which were well tolerated (Scheme 1, products 4 and 5

• outstanding results were achieved in the N-formylation of indoline (Scheme 1, formamide 10). The present methodology could also be effectively applied to the synthesis of N-formylmorpholine (Scheme 1, product 11). Aliphatic primary amines can be more challenging substrates [22]. In fact, when the reaction was

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• 31P NMR chemical shifts were calculated using the plane-wave density function theory (DFT) code CASTEP v20.11 (see Supporting Information File 1 for full computational details) [45]. In the absence of an experimentally resolved crystal structure for g-h-PCN, we followed a similar methodology to our

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• in a continuous flow electrochemical process, the flow methodology was applied to the self-annulation of cinnamaldehyde, a classical NHC-catalyzed reaction (Scheme 4). All the experiments were carried out using a solution of 0.1 M BMImBF4 in acetonitrile (20 mL) as catholyte, stainless steel as

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• methodology is decorated with several advantages like scalability and selectivity. Additionally, no column chromatographic purification was required at any stage and each step was high yielding. After the synthesis of starting materials, the Morita–Baylis–Hillman reaction was explored for C-3

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• bearing a perfluoroalkyl or perfluoroacyl group [27][28][29][30]. Furthermore, they extended this methodology to tandem cyclization to provide fused difluoromethylene-containing heterocycles [31]. In consideration of these facts, we studied the cathodic reduction of 1 using a mediator. Indirect cathodic

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• halogenation reactions or oxidation. For these reasons, it would be ideal to develop an efficient methodology that allows for the generation of perfluoroalkyl radicals in a mild, redox- and pH-neutral manner, without the assistance of external photocatalysts, heavy metal catalysts, or further additives. Thus

• readily, and is subsequently followed by a hydrogen atom transfer (HAT) process aided by the “dummy group” radical. These reagents thus fit the paradigm of a green methodology as their implicit design and photoactivity allows them to react without the use of external metal catalysts. The intrinsic

• , trifluoromethyl radicals and its longer-chain analogues, share a common electrophilic character and a stabilizing stereoelectronic effect [14], we envisioned that the “dummy group” methodology could be translated into the formation of sought after perfluoroalkyl radicals (Scheme 1). In this work, we report the

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• , a synthetic methodology for the preparation of 1–3 was developed by Warrener and co-workers by a Zn/Ag couple debromination [13][14][15]. However, this methodology has some disadvantages, such as tedious preparation of the catalyst, the use of dry solvent and expensive silver acetate as well as side

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• corresponding products 5m with 92% yield, respectively. In addition to this, aliphatic aldehydes (cyclohexanecarbaldehyde, butyraldehyde) were well tolerated under the standard reaction conditions to produce the product 5n and 5o with good yield. The substrate scope of this methodology was extended to chloro

• (5m). Conclusion In summary, we have successfully developed efficient methodologies for synthesizing 1,2-disubstituted benzimidazoles and quinazolin-4(3H)-one derivatives under mechanochemical (ball milling at 21 Hz) conditions in the presence of DDQ. The developed methodology can be considered as a

• green and eco-friendly methodology due to its solvent-free and metal-free nature. So, it can also be regarded as an alternative pathway to the traditional solution-based protocols. We anticipate that our developed strategy will have a substantial impact on the field of organic synthesis. Our work on

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• reactions pyruvate showed increased affinity towards the investigated enzymes. Given the metabolic importance of pyruvate [33][34][35], it may be of interest to test different pyruvate converting enzymes if this trend is confirmed. Experimental Methodology Genes and expression strains The gene of the

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• methodology for the preparation of analogues of karrikins with one sulfur atom in position C2 or position 6, or two sulfur atoms in both positions was improved; however, observed biological activities towards AChE were rather low. Structures of naturally occurring karrikins. Target compounds with highlighted

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• proves that two equivalents of 3-phenacylideneoxindole are required for reductive cyclodimerization. Conclusion In conclusion, we have successfully developed a simple and efficient methodology towards the one-pot synthesis of dispirocyclopentanebisoxindole derivatives through base-catalyzed reductive

• methodology and structural diversifications of this moiety are underway in our laboratory. Experimental General method: All commercially available chemicals were purchased from Aldrich, USA or Spectrochem, India, and used without further purification. All solvents were used as received. The progress of the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• dichromate as oxidizing agent in the presence of sulfuric acid, instead of acetic acid, to obtain compound 10 in 62% yield within a shorter reaction time (Table 1, entry 2) [48]. The methodology using sodium dichromate and sulfuric acid was adapted to the industrial scale production of vitamin K3 (10

• generated from the carboxylic acid through decarboxylation mediated by [Ag+]-peroxydisulfate, followed by their coupling with the quinone, providing the respective alkylated product. One of the first practical applications of this methodology to produce menadione (10) was described by Ashnagar and co

• published an alternative and sustainable methodology, using phenyliodine(III) bis(trifluoroacetate) (PIFA) as an oxidizing agent of the demethylation reaction [86]. The hypervalent iodine(III) proved to be a good oxidizing agent in the formation of 10 (92% yield) (Table 3, entry 2). According to the authors

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• reaction to furnish the corresponding 5-unsubstituted dihydropyrimidinone-4-carboxylate derivative 8 in good yield (entry 1, Table 1). Encouraged by this observation, we tested the generality of this methodology by employing various electron-donating as well as electron-withdrawing groups on the aryl ring

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• the 1,4-position of 1. On the other hand, the double bond of 2 hardly interacted with the 9,10-position of 1, because of the steric effect induced by the cage host A. This methodology was also compatible with several other anthracene substrates with different substituents at the 9-position. But when

• mode, the molecular container selectively binds with and shields a certain part of the guest molecule and leaves the remaining part exposed to the reaction medium. This methodology was firstly applied to the site-selective reduction reaction mediated by a cyclodextrin host. In 1991, the Takahashi group

• cyclodextrin as the anchoring template. For example, cyclodextrin would fix the steroid substrate with a certain set of orientation, which exposes one certain C–H bond to the metalloporphyrin catalytic moiety and produces site-selective oxidized product. As shown in Figure 8, in this methodology, the steroid

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• electronic nature. Environment-friendly reaction conditions, easily accessible substrates, and broad substrate scope highlight the practicality of this methodology. Results of the acid-catalyzed intramolecular hydroindolation of cis-β-(α′,α′-dimethyl)-4′-methindolylstyrenes 17 were reported by Stokes and co

• this methodology to related substrates with free indolyl NH as such reactions resulted into a complex mixture (not shown here), possibly due to the decomposition of the substrates. Nevertheless, the same regioselectivity was observed when the FC-acylation of N-protected 3-(4-indolyl)propanoic acids 28g

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• , Chinchilla et al. reviewed the Sonogashira reaction demonstrating its wide generality and applicability, and the protocol has become a booming methodology in synthetic organic chemistry [6]. Thereafter, the same authors again compiled the Sonogashira reaction covering literature up to 2011 attesting the

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• determined the stereoselectivity of the reaction arises from the unattractive interactions imposed from the sterically hindered endo-face of the bicyclic alkene. The mechanistic insights gained from this combined experimental and theoretical study will facilitate further future methodology development in

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• asymmetric organocatalytic methods to assemble biologically relevant compounds is highlighted by a review article devoted to the syntheses of coumarin derivatives [16]. Conjugated additions of stabilized nucleophiles are the cornerstone of organocatalytic methodology. Recent advances in this area are covered

• catalysis relies on the deprotonation of one of the substrates, but basic conditions may limit the applicability of this methodology. A unique base-free variant of chiral phase-transfer catalytic alkylation of 2-oxindoles was developed by Connon and co-workers [23]. Pentacarboxycyclopentadienes are a unique

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• following treatment of acid 5 with hydrazine hydrate, followed by hydrazone formation with the corresponding aldehyde. When subjected to the reaction conditions, oxadiazoles 2k and 2l were obtained in low yield over this multi-step sequence. While unsuitable for large scale reactions, this methodology may

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• operations and waste generation, this methodology should rapidly find applications in organic chemistry laboratories but also possibly on industrial scale. Experimental Typical experimental procedure with dicyclohexylamine 1: Dicyclohexylamine (37 mg, 0.21 mmol, 1 equiv) and 2-methoxynaphthalene (33 mg, 0.21

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• new C5–C6-unsubstituted 1,4-DHPs under ultrasonic irradiation. The important focus of the methodology was to develop an environmentally friendly protocol with a short reaction time and a simple reaction procedure. The other advantages of this protocol are a wide substrate scope, a very good product

• of green chemistry [21]. The application of ultrasound in “traditional” reactions results in a lower reaction time, higher conversion, and simpler methodology and is termed sonochemistry. Ultrasonication is a modern trend in synthetic chemistry that supports the objective of green chemistry, namely

• with this methodology, as shown in Figure 5. The synthesized products were characterized by 1H NMR, 13C NMR, HRMS, and melting point analysis. The structure of the compounds was also confirmed by single-crystal XRD analysis of 4a (CCDC1949329, Figure 6). Plausible mechanism A plausible reaction