Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• plausible pathways. Attractive elements include the regioselective and straightforward direct synthesis of fully substituted 1,2,3-triazoles, which are otherwise difficult to access, from readily available starting materials. Keywords: [3 + 2] cycloaddition; defluorination; fully decorated 1,2,3-triazoles

• -promoted [22] azide–alkyne cycloaddition reactions [17][23][24]; however, most of these strategies use high temperatures [21][25]. Herein, we report the discovery of a novel, one-step regioselective method under mild conditions to obtain 1,4,5-trisubstituted-1,2,3-triazoles from gem-difluoroalkenes

• ] cycloaddition reaction utilizing gem-difluoroalkenes, which inherently exhibit attenuated activity compared to the activated α-CF3 carbonyls. This report provides a highly regioselective and novel way to access C-4-morpholine-functionalized fully decorated 1,2,3-triazoles from gem-difluoroalkenes and organic

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• cyclization transformation involving activation of the electrophilic sulfur reagent by PhSePh with the assistance of TMSOTf to form transition state I. Intermediate II formed through capturing of sulfonium by selenium. Then, II reacted with 136 to give regioselective cyclic thiiranium ion III. Nucleophilic

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• tosylation of the primary alcohol produced 4.8. The epoxidation of 4.8 occurred by reaction with t-BuOK in THF, thus producing 4.9 as a chiral electrophile. The regioselective opening of the epoxide is achieved by adding the octadecanol sodium salt. The intermediate was debenzylated by catalytic

• also achieved in the last step (Figure 5) [73]. DIBALH (diisobutylaluminium hydride) in toluene was added to hexadecanol in dichloromethane at 0 °C (Figure 5) to form in situ a lithium alcoholate. Then, S-glycidol was added at rt to produce in 50% yield the diol 5.2 after a regioselective opening of

• protection was not regioselective (a mixture of primary and secondary protected alcohols was formed). The acylation of the secondary alcohol was then achieved with acetic anhydride in the presence of pyridine. Then, the deprotection of the trityl moiety of compound 12.4 by catalytic hydrogenation failed

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• have broad applications in synthesis. In 2019, Cai et al. developed a regioselective ligand-promoted CDC reaction between unactivated C(sp3)–H/C(sp3)–H bonds (Scheme 18) [79]. Different types of C(sp3)–H bond substrates, including cycloalkanes, cyclic ethers, and toluene derivatives without any

• catalyst. The authors demonstrated that the introduction of the two indoles occurs in two distinct steps, a radical process and a Friedel–Crafts alkylation reaction. Coumarin and flavonoid derivatives are very valuable precursors in drug synthesis. In 2015, Ge et al. developed the regioselective and atom

• chemoselective and regioselective CDC between pyridines and ethers, which used Sc(OTf)3 as the catalyst and DTBP as the oxidant (Scheme 36) [101]. This strategy allowed the synthesis of a series of α-substituted pyridine derivatives. The control experiments showed that the mechanism may proceed via a radical

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• Toulouse, France University of Tunis El Manar, Laboratory of Organic Chemistry, Faculty of Sciences, Campus, 2092 Tunis, Tunisia 10.3762/bjoc.19.93 Abstract A highly α-regioselective N-nucleophilic allylic substitution of cyclic MBH alcohols and acetates with imidazole or benzimidazole, in toluene at

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• . Functionalization of the carbocyclic ring of substituted indoles. Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles. Anilines and α-naphthols as potential nucleophiles. Solvent-controlled regioselective aza-Friedel–Crafts reaction. Generating central and axial chirality via aza-Friedel

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• their ability to participate in either redox step of the catalytic cycle [42][43][44][45]. For example, the main use of α-amino acids in syntheses via photoredox catalysis is as readily available precursors of regioselective α-amino radicals by decarboxylative transformations, by oxidation of the

• ]. Regioselective palladium-catalyzed prenylation of 2 with prenylboronic acid pinacol ester and subsequent hydrolysis with LiOH provided the linear prenylated acid 4 in good yield. Coupling acid 4 with N-hydroxyphthalimide using DCC and a catalytic amount of DMAP afforded the key intermediate 5 in 59% yield. With

• a tentative mechanism (Figure 2). First, the radical cation I was generated via the oxidation of indole 5 by the excited Ir-based photocatalyst, followed by sequential regioselective proton transfer on the benzylic dimethylallyl unit C–H bond of the C4 side-chain, thereby generating II. Here, the

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• reactivity of their alcohol functions. This allows regioselective chemical modification at either the primary or secondary rim [13]. As a result, these molecular hosts can be specifically linked either covalently or noncovalently to a wide variety of ligands. CDs are a significant part of almost all areas of

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• photoactive arrangement, a single-crystal-to-single-crystal regioselective [2 + 2] photodimerization reaction was accomplished by irradiating at 365 nm using a 6 W UV lamp. This light-triggered reaction led to the photoconversion of the threaded styrylpyridinium motifs into the corresponding interlocked

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

• challenge. In this context, a regioselective alkylation of ortho-unsubstituted or substituted unactivated pyridines with acrylates and acrylamides under Rh(I) catalysis has been demonstrated by Ellman and co-workers [59]. The authors observed that in the presence of [Rh(cod)Cl]2 as catalyst, dppe as ligand

• tricyclic imidazonaphthyridinone derivative having antibacterial properties, with low catalyst loading (0.1 mol %) (Scheme 20b). Later, in 2014, the same authors, using an amide as directing group (DG), developed a protocol for the regioselective C3-alkenylation of pyridines through syn-addition of alkynes

• ). In 2015, a palladium-catalyzed cross dehydrogenative coupling of pyridine N-oxides with toluene for the regioselective arylation and benzylation of pyridine N-oxide was reported by Khan and co-workers [92] (Scheme 23). The authors have shown toluene 117 when used as benzyl and aryl source remained

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability. Keywords: C–H functionalization; imidazo heterocycles; photoredox; regioselective; relay catalysis; Introduction Among all N-fused heterocycles, imidazo[1,2-a]pyridines (IPs) are the prevalent

• particularly familiar due to their biological and medicinal attributes [7][8][9][10][11]. Not surprisingly, the C-3 functionalization of IPs is a continuing interest of research in the synthetic community [12][13][14][15][16]. Despite many successful strategies in this field, the regioselective C–H

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• is entirely regioselective for the formation of a 1,2,4-trisubstituted pattern. The observed regioselectivity arises from the preferential migratory insertion of the aryl group distal to the bridgehead substituent. In 2010, Ogata and Fukuzawa explored the Ni-catalyzed two- and three-component

• ) and O-benzoylhydroxylamine derivatives 54 (Scheme 9) [43]. While the scope of bicyclic alkenes was quite extensive with aza-, carbo-, and oxabicyclic alkenes being amenable to the reaction, electron-deficient substrates resulted in lowered yields. Of note, the reaction is highly regioselective with

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• , the group of Li disclosed the Cp*Rh(III)-catalyzed regioselective trifluoromethylthiolation of N-substituted indoles with (substituted) pyridines or pyrimidine as the directing groups (Scheme 10) [123]. The selective trifluoromethylthiolation of indoles at the C2 position was achieved in the presence

• used. Regioselective Cp*Rh(III)-catalyzed directed trifluoromethylthiolation reported by the group of Li [123]. Cp* = pentamethylcyclopentadienyl. Cp*Co(III)-catalyzed ortho-trifluoromethylthiolation of 2-phenylpyridine and 2-phenylpyrimidine derivatives reported by Wang and co-workers [124]. aCH2Cl2

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• introduced to the corresponding α- and β-fluorinated aminophosphonates 4, 6 (Scheme 1) by regioselective deoxyfluorination reactions of α-hydroxy-β-aminophosphonates 2 [24][25][26]. Next, the conditions for the solvolysis were carefully assembled (Scheme 2). The optimized reaction conditions included 8 equiv

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ] between halide 37 and phenol 38 leading to the formation of diaryl ether 39, which was subjected to a regioselective iodination reaction to give compound 40. Conversion of the nitrile in compound 40 into the corresponding aldehyde 41 followed by Z-selective Still–Gennari olefination gave the cis α,β

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• 50% overall yield. For the synthesis of albolic acid (178) and ceroplastol II (179), the side chain was introduced by deprotonation and addition of the corresponding aldehyde. After dehydration of the subsequent alcohol and conjugated addition of Me2CuLi, the regioselective reductive opening of

Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs)

• Swantje Lerch,
• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2023, 19, 212–216, doi:10.3762/bjoc.19.20

• the different Lewis acids, the reaction is regioselective for the para-position. TAAIL 6 was chosen for further optimizations because it appeared to be a slightly better reaction medium compared to the other TAAILs. To optimize the yield of the reaction and to reduce the reaction time, different

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• of an aldehyde resulting in a regioselective aldolization [29]. Thereafter, we hypothesized converting cyclopentadiene 6b into 2,5-cyclohexadienone 5 by a sequence involving the oxidation into dialdehyde 7 and treatment with pentan-3-one to enable sequential steps of aldolization and crotonization

• exposing 2 to the combination of reagents tri(n-butyl)allylstannane/n-BuLi (2 equiv) followed by the treatment with MeI, the crotyl derivative 8 was directly isolated in 55–60% yield (5 g scale) via the regioselective methylation of the intermediate vinylogous enolate 10·Li. The preparation of aldehyde 9

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• HFIP. The regioselective amination of benzylic positions in alkylarenes [82] and ethers [83] directed by steric effects was achieved by the development of sterically hindered “bowl-shaped” imide-N-oxyl radical precursors (Scheme 7). The presented example with a sterically hindered N-hydroxyimide

• -hydroxylation of lactams under phase-transfer organocatalysis conditions employing a chiral quaternary ammonium ion salt. Selective CH-oxidation of methylarenes to aldehydes or carboxylic acids. An example of the regioselective CH-amination by a sterically hindered imide-N-oxyl radical precursor. CH-amination

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• envisioned for this carbocation (e.g., a nucleophilic attack of formic acid to give a formate ester), only alkene formation was observed in this system. Interestingly, the deprotonation step is completely regioselective, giving the more highly substituted endocyclic trisubstituted alkene found in 8 as

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• yields [22]. The switch from 2-tetrahydropyranyl to tert-butyloxycarbonyl protected compound 19 was required for an efficient installation of the exocyclic amine via regioselective nitration in the presence of trifluoroacetic anhydride (TFAA) and tetrabutylammonium nitrate (TBAN) to give a mixture of the

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• key organic intermediates in the drug discovery and process chemistry [4][5][6]. Chiral metal–salen complexes were designed for catalyzing reaction processes that resulted in good yield, high regioselective and enantioselective control for the asymmetric ring opening of terminal epoxides. Various

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• of the hydroxy group to the terminal double bond of the allene in compound 3. Another key step is the Ti(III)-mediated straightforward synthesis of this α-hydroxyallene, which could be achieved through a regioselective Barbier-type coupling of a propargylic halide (1-bromo-2-butyne) with the aldehyde

• compound 2. The isopropenyl residue of the target compound 1 was assembled through a two-step sequence. The first one was the addition of an excess of methylmagnesium bromide to the ester 2, that completed the carbon skeleton. The second step was the pH-controlled regioselective dehydration of the tertiary