Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• aryl ring smoothly underwent this asymmetric reduction, affording the desired indolines in 95–99% yield and 90–96% ee within 3 hours. Replacing the 3,3-difluoro substituents by two methyl groups in the starting indole as well as the alkyne part by a phenyl group, the reaction still gave good results

• enantioselectivity of the reaction. The role of fluorine and alkyne in the reaction should be close to the gem-dimethyl moiety and the phenyl group in the previous research [32]. Conclusion In summary, we developed a convenient method for the synthesis of chiral difluoroindoline compounds for the first time. With a

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• process. The [2 + 2] CA–RE sequence proceeds successively, as depicted in Scheme 1, where electron-donating groups are denoted as EDGs. During the [2 + 2] CA process, the nucleophilic attack by the terminal alkyne carbon of an electron-rich alkyne on an electron-deficient alkene, such as TCNE and 7,7,8,8

• TCNQ with electron-rich alkynes, the alkyne terminal carbon executes a nucleophilic attack on the exocyclic carbon of the dicyanovinyl (DCV) group of TCNQ, affording dicyanoquinodimetanes (DCNQs) [12][13]. Intense ICT bands of TCBD and DCNQ are observed at around 450–470 nm and 680–710 nm, respectively

• [4][5][7]. Notably, the N,N-dimethylanilino (DMA) moiety activates the reactivity of the neighboring alkyne moiety so strongly that the [2 + 2] CA–RE reactions with electron-deficient olefins proceed seamlessly [15][16] even when the terminus of the alkyne moiety is substituted by a cyano group [17

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• -olefination reaction was first discovered by Ramirez and co-workers [22] and used in the first step of the Corey–Fuchs reaction that ultimately provides an alkyne [23]. To elucidate the properties of the donor part itself of the pyrrolo-annelated IF-DTF systems, we prepared compounds 16 and 17 containing a

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• alkylphosphine, an aldehyde and an alkyne [32]. Another example resulting from phosphine addition to α,β-unsaturated aldehydes was published shortly afterwards [33]. Phosphonium carboxylate zwitterions have been obtained by the reaction of phosphines with acrylic acid [8] and ortho-carboxylated arylphosphines

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• possibility of obtaining the products of alkyne hydration with analogous or improved yields, using less hazardous precursors to generate the reactive species in situ. In particular, for terminal arylalkynes, the electrochemical route proved to be advantageous, yielding preferentially the hydration products vs

• the aldol condensation products. Importantly, the ability to recycle the ionic liquid in subsequent reactions was successfully demonstrated. Keywords: alkyne hydration; boron trifluoride; electrochemical synthesis; ionic liquids; Introduction Alkynes are fundamental starting materials towards more

• well-known and useful reaction in organic chemistry, affording carbonyl compounds based on an atom-economical approach. Indeed, the addition of water to the triple bond of a terminal alkyne leads to the formation of the corresponding methyl ketone or aldehyde, in the case of Markovnikov or anti

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• system (G) was first investigated by Albrecht et al. in 2008 [23]. Because the heterocyclic precursors needed to prepare 1,2,3-triazol-5-ylidenes are readily available through the [3 + 2] cycloaddition of an azide and an alkyne, these compounds are currently the most popular MICs for catalytic and other

• -disubstituted-1,2,3-triazole derivatives is readily achieved via the copper(I)-catalyzed [3 + 2] cycloaddition of an azide and a terminal alkyne (CuAAC) [63][64][65]. A further alkylation of the N3 position with an alkyl halide is an equally straightforward procedure that ultimately affords a large assortment

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• 2,2'-dihalogenated biphenyls 4 as starting materials [24][25]. Although the cobalt-mediated alkyne trimerization route frequently used by Vollhardt and co-workers is not the first choice for the synthesis of the biphenylene itself, it has led to the synthesis of structurally demanding substituted

• biphenylenes and the emergence of a family of polycyclic hydrocarbons called [N]phenylenes. The utilization of cobalt-mediated alkyne trimerization facilitated the synthesis of [N]phenylenes exhibiting diverse structural configurations, including linear 7, angular 8, zig-zag 9, bent 10, branched 11, and cyclic

• 83 was achieved through a Co-mediated alkyne trimerization process. Finally, the synthesis of the targeted boron-doped extended POA 84 was carried out with a yield of 61%, following a series of reactions including cyclocondensation with BBr3 and mesitylation. Since the "v" and "z"-shaped POAs could

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• of the final [2]rotaxanes by active template copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) as key step of the synthesis. HRMS and NMR experiments have been performed to confirm the formation of the interlocked structures. Keywords: active-metal template; clipping; copper(I)-catalyzed alkyne

• primary alkyl bromides [36] and cooper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) click chemistry [37]. In all these cases a templated metal ion–macrocycle complex is used to catalyze the rotaxane formation by connecting two components of the dumbbell-shaped molecule (Figure 1a). In this context, we

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• complex obtainable via a straightforward synthesis, with improved solubility, concerning our previous Co(II) complexes [21]. Thus, the new Co(II) complex bears two 1-benzyl-4-(quinolin-2-yl)-1H-1,2,3-triazole (BzQuTr) units, that were obtained through a copper-catalyzed alkyne–azide cycloaddition (CuAAC

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• functionalization of optically active polymers [106]. Theato and co-workers introduced vinyl/alkyne-bearing poly(vinyl ether)s [107], poly(vinylcyclopropanes) [108], and poly(allyl 2-ylideneacetate) [109] as promising new platforms compatible to thiol–ene chemistry. Atom transfer radical addition (ATRA) is another

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• , which is an internal alkyne instead of a terminal alkyne, but no desired product was obtained. Next, we explored the substrate scope of 2-methylquinolines under the standard conditions. 2-Methylquinoline bearing different substituents at various positions gave the corresponding products with moderate to

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

• -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

• generated via an azide–alkyne cycloaddition or a multicomponent reaction between carbonyls and azides [17]. α-Trifluoromethyl (α-CF3) carbonyls were recently utilized to generate NH-1,2,3-triazoles and fully substituted 1,2,3-triazoles [28][29]. However, there are no reports of a formal [3 + 2

• –elimination of morpholine to gem-difluoroalkene 1 affording INT-1, which can generate product 3 via two routes (Figure 5). Route A entails the formation of an aminoalkyne intermediate, INT-2, which can participate in a [3 + 2] azide–alkyne cycloaddition to form the final product 3. Alternatively, vinylic

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

• or 14, caused polarization of the S–N bond and produced an electrophilic intermediate I. Through the nucleophilic attack of the alkyne on I, cation II was generated, leaving Al-coordinated phthalimide/succinimide III. Finally, 4-endo-trig spirocyclization of II rendered the unstable intermediate IV

• of polarized ketene-N,O-acetal to the alkyne β-carbon and trapping of the sulfonium cation at the alkyne-α-carbon afforded 5-(arylthio)-3,6-dihydropyridin-2(1H)-one 148. The coordination of a sulfonium electrophile to the C–C triple bond of 1-I occurred through cyclopropyl intermediate 1-I. The

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

• catalyst when products were obtained with excellent enantioselectivity (92% ee) (Scheme 46). 2.3 [3 + 2] Cycloaddition reactions In a [3 + 2] cycloaddition reaction, a three atoms dipolar moiety (1,3-dipole) adds across two atoms of an alkene or alkyne (1,3-dipolarophile) (Scheme 47). It is also known as

• -donors on the catalytic activity of NHC–Cu(I) complexes for azide–alkyne [3 + 2] cycloaddition reactions [67]. They determined binding constants of four NHC–CuCl complexes with two N-donors, which revealed that addition of phenanthroline to the NHC–CuCl enhanced the catalytic activity manifold. In fact

• and co-workers [68] developed a new series of heteroleptic bis(NHC)–Cu(I) complexes and a mixed NHC–Cu–phosphine complex and employed these complexes as catalysts for azide–alkyne [3 + 2] cycloaddition (Scheme 50). These cationic heteroleptic bis(NHC)–Cu complexes 131 are highly active for this

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• azide was combined with a subsequent copper-catalyzed (3 + 2) cycloaddition with terminal alkynes. This one-pot process was developed with a simple model alkyne, but then applied to more complex alkynes bearing enantiopure 1,2-oxazinyl substituents. Hence, the precursor compounds 1,2-, 1,3- or 1,4-bis

• discovery of the copper-catalyzed alkyne azide (3 + 2) cycloaddition (CuAAC) [3][4], has dramatically changed the approaches to many problems in chemistry, supramolecular chemistry, materials science, biological chemistry and related fields (selected reviews: [5][6][7][8][9][10][11][12][13][14][15

• nucleophilic substitutions employing sodium azide and organic substrates with potential leaving groups have been reported. The resulting organic azides were trapped in situ by a suitable alkyne to give the 1,2,3-triazoles [26][27][28][29][30][31][32][33][34][35][36]. Fairly recent review articles summarize

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• -catalyzed processes for accessing indoles have become attractive alternatives over the past decades [19][20][21][22][23][24]. Besides Larock's indole synthesis employing alkyne anellation [25] and Cacchi's cyclization of ortho-alkynylanilines [20][22] catalytic syntheses of indoles from alkynes have become

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

• afford allyl ethers. Alkyne C(sp)–H bonds are reactive, and the challenge in the cross-coupling of C(sp)–H and C(sp3)–H bonds is to control chemoselectivity. In this context, Liu et al. reported a Cu(I)/Ga(III)-catalyzed trityl ion-mediated direct CDC of the C(sp3)–H bond of THF with C(sp)–H bonds of

• to afford internal alkynes from substrates with the C(sp3)–H bond mainly located in the α-position to N, O, or S atoms. This method provides a direct and atom-economical alternative for the construction of structurally complex alkyne compounds (Scheme 26) [87]. In addition to iron, various other

• transition metals such as Cu, Pd, and Ag are also suitable to catalyze the reaction. In 2012, Xiang et al. reported the CDC of aryl ethers with C(sp3)–H bonds adjacent to the ether oxygen with terminal alkyne C(sp)–H bonds, which provides a new approach for the construction of the C(sp3)–C(sp) bonds (Scheme

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

• products, demonstrating a clear preference for addition to alkenes even in the presence of alkyne functionalities. Due to basic conditions of the reductive quenching (RQ) route, the formation of lactone side product 30h could be observed with a carboxylic acid functionality. In the absence of Et3N, the

• mechanism follows a ‘monophotonic’ oxidative quenching (OQ) route in which [FeIII(btz)3]3+ is oxidatively quenched to [FeIV(btz)3]4+ by the alkyl halide substrate after excitation with green light. After addition of the alkyl radical to the alkene or alkyne substrate, the catalyst is regenerated by

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement. Keywords: 1,4-dihydropyridine; electron-withdrawing alkyne; formal [2 + 2] cycloaddition; Huisgen's 1,4-dipole; isoquinoline

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

• state 98). The substrate scope comprised mainly varying aryl or heteroaryl-substituents at the alkyne moiety that imparted high degrees of enantioselectivities to the products (Scheme 22b) [52]. In 2022, Huang and co-workers demonstrated an atroposelective construction of 3,4’-indole-pyrazole frameworks

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

• involves the initial formation of π-complex A via activation of the alkyne by Pd. Then, in case of N-methylpyridinium salt 82, in presence of CuBr the pyridine–Cu(I) complex 87 is formed through C–H activation that further undergoes nucleophilic attack to the coordinated alkyne in a trans-manner to give Pd

• scope and limitations of the dual catalyst Ni–AlMe3 and also the sensitivity of the reaction towards the steric environment on the pyridine ring. The complex 112 undergoes oxidative addition followed by an alkyne insertion reaction to give intermediate 113, which after reductive elimination provides the

• alkynes 179. Different directing groups 178 were employed resulting in diversified products 180. The proposed mechanism (Scheme 35b) involves coordination of rhodium with isonicotinamide 178 and subsequent ortho-C–H activation generating the five-membered rhodacycle 183. Next, first alkyne 179 insertion

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• hexarylbenzene derivative 30, An and co-workers also reported an azocine-embedded, [5]helicene containing NG 31 [41]. The precursor 30 was synthesized by Diels–Alder reaction of aza-alkyne 28 and tetracyclone 29. By treating compound 30 under Scholl reaction conditions, the helical structure 31 was obtained

• helical NG 44 containing [6]helicene structure and an azulene unit (Scheme 5). Through a two-fold Diels–Alder cycloaddition from 1,4-bis(2-ethynylphenyl)buta-1,3-diyne (41) and tetracyclone 11, alkyne 42 was obtained in an 83% yield. Then unique diiodide precursor 43 was obtained by ICl-mediated

• -workers synthesized a helical bilayer NG by using helicene in the initial step as the linker to fuse two HBC units [48]. As shown in Scheme 6, starting from the helical alkyne 54, Sonogashira coupling with 4-tert-butyliodobenzene (55) afforded structure 56 in a 77% yield. Subsequent Diels–Alder reaction

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• ) [66]. Variations of this reaction include alkyne metathesis [67] and carbonyl metathesis [68]. Ring-closing metathesis (RCM) gave access to a series of dibenzo[b,f]heteropines, as reported by Matsuda and Sato [31] (Scheme 25). The authors synthesised a series of Si-, Sn-, Ge- and B-tethered dienes 118

• synthesising the tethers and RCM products are reported, the method does not currently allow for the synthesis of unsymmetrical compounds. 3.6 Alkyne–aldehyde metathesis Bera et al. [69] reported on the synthesis of a series of 10-acyldibenzo[b,f]oxepines 125 by alkyne–aldehyde metathesis catalysed by iron(III

• ) chloride (Scheme 26). Alkyne–carbonyl metathesis is proposed to proceed via [2 + 2] cycloaddition and –reversion steps, catalysed by a Brønsted or Lewis acid, with the catalyst proposed to form a σ-complex with the carbonyl group and/or a π-complex with the alkyne [68]. 3.7 Hydroarylation The construction

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• had low ee values, the trans-products showed better enantioselectivities (up to 78%). Their control experiments suggested that the Ru enolate, formed by the conjugate addition of the alkyne to the enone, plays a significant role in the following aldol reaction. Later, Tian et al. have also employed a

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

• initiates with the in situ reduction of Ni(II) to Ni(0) followed by the side-on coordination of the alkene and alkyne substrates to the metal center with subsequent oxidative cyclometallation to form a nickel metallacycle, similar to several reported Ni-catalyzed [2 + 2] cycloadditions [29][30]. Rather than

• the coordination of the alkyne 17 and alkene 1 to the Ni(0) center, followed by oxidative cyclometallation, yields the following nickelocycle 24. Unlike Cheng’s 2003 report, which proposes subsequent β-oxygen elimination (Scheme 1) [31], alkoholysis by MeOH affords an alkyl(methoxy)nickel intermediate

• state, followed by coordination to the alkyne generates intermediate 109. Migratory insertion of the alkyne results in the ruthenacycle 110. Subsequent reductive elimination generates putative allyl vinyl ether 111 and regenerates the active ruthenium complex. The allyl vinyl ether intermediate