Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• catalysis encompassed various azoles such as pyrazole, indazole, and (benzo)triazole, exhibiting high Z-selectivity. In addition, Cao et al. reported a gold-catalyzed addition of 5-substituted tetrazoles to terminal alkynes [11]. Analogous hydroazolation reactions of alkynes have also been achieved under

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• intermediate B should be ruled out from this methodology (Scheme 4b). The product Z-6i was subjected to the standard conditions, but Z-6i was obtained in 100% recovery yield. Therefore, the E/Z selectivity of the MCRs with allenes could be determined by the allylic substitution process (Scheme 4c). Using HPd

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

• configuration of the products by modifying the substituents on the nitrogen of the pyridinium salts. Further, the method showed a wide substrate scope for both the Z- and E-alkenylated products in which Z-selectivity was achieved when N-methylpyridinium salts were used and E-selectivity when N-benzylpyridinium

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

• acrylamide derivatives [140]. Using the same directing group, a panel of α-arylacrylamide derivatives 39a–f was successfully functionalized with a high Z-selectivity (yields up to 98%, Scheme 18). Both, thermal reaction conditions (DMSO at 70 °C for 16 h) and microwave irradiation (100 °C using microwaves in

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• and with a Z-selectivity of >98% [54]. In contrast, Amorelli, Collins, and co-workers performed a ring-closing metathesis for the synthesis of macrocycle 72 from diene 70 at high temperatures of 150 °C in only 5 min without removal of formed ethylene (Scheme 17) [55]. Under these conditions, the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• good yields and with high (Z)-selectivity. The proposed mechanism involved the oxidative addition of the distal C–C bond to palladium, followed by a nucleophilic attack at the less hindered carbon atom of a 2-fluorinated palladium–π-allyl complex. Other examples of Pd-catalyzed ring-oрening reactions

• reaction of 2-(2,2-difluorocyclopropyl)naphthalene (167) with sodium arylsulfinates 168 under palladium catalysis afforded the 2-fluoroallylic sulfones 166 in moderate to good yields with (Z)-selectivity. This method showed a good compatibility with a broad range of substrates and substituents. As

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• equiv) in dichloromethane. The reaction was slow and required heating (50–65 °C) for 26 h to reach a 75% conversion and afforded a mixture of E/Z-1a in 60% yield. However, a low E/Z selectivity (40:60) was observed (Table 1, entry 1). When using neat benzylic alcohol, completion was achieved after 20 h

• investigated with hydrobromic acid (HBr 33 wt % in AcOH, 2.3 equiv) in diethyl ether (Table 1, entry 4). This reaction proved faster and reached completion after 45 min at 20 °C, giving product 1d with an excellent yield of 94% and an E/Z selectivity of 89:11. The isomers could be separated and crystals of the

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• regeneration of the α,β-unsaturated 2-acyl-1-methylimidazole moiety was performed in high yield and E/Z selectivity via a two-step protocol. The resulting Michael acceptor was then engaged in an ECA to afford the expected 1,3-dimethyl product in 69% yield and a good diastereomeric excess of 94% (Scheme 17

Progress in metathesis chemistry

• Karol Grela and
• Anna Kajetanowicz

Beilstein J. Org. Chem. 2019, 15, 2765–2766, doi:10.3762/bjoc.15.267

• been made over these years. For example, a number of new highly stereoselective Ru and Mo catalysts have been introduced, solving the problem of E- and Z-selectivity. Some tagged Ru catalysts can be applied in water and even in biological systems, while Mo and W alkylidenes packed into innovative wax

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• ] extended this approach to the directing-group-assisted copper-catalyzed trifluoromethylation of electron-deficient alkenes (Scheme 72b). Moreover, α-aryl and α-alkyl-substituted acrylate derivatives could be used as substrates to form the C(sp2)–CF3 bond with a complete Z-selectivity. A radical species

• reaction proceeded efficiently for a wide range of alkyl and aryl-substituted α,β-unsaturated carboxylic acids derivatives with excellent E/Z selectivity (Scheme 76). It's worth mentioning that the addition of Ag2CO3 additives was crucial for promoting the decarboxylation of α,β-unsaturated carboxylic

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• % conversion, respectively, in four days. In the CM of allylbenzene (13) with cis-1,4-diacetoxy-2-butene (14, Scheme 4), the fluorinated complexes 3a–5a and 3b–5b exhibited activities comparable to GII-SIMes and HGII-SIMes, showing higher Z-selectivity at conversions above 60%. For example, catalyst GII-SIMes

• improve E/Z selectivity in CM reactions and diastereoselectivity in RCM reactions altering the environment of key metathesis intermediates. Complexes 24 and 25 were found to exist in solution as a single rotational isomer having the benzylidene moiety located under the mesityl group, and for complexes 24b

•  5, entry 2) and in the CM of 13 with 14, but with a slightly lower Z-selectivity (Table 5, entry 3). Finally, in the presence of catalysts 120, 121 and 123, diastereoselectivities higher than those achieved in the presence of GII-SIMes, HGII-SIMes and IndII-SIMes were observed in the

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• without any solvent (Table 1). In general, we noticed that more polar solvents (high dielectric constants) favour Z selectivity and a higher overall conversion, whereas the use of less polar or no solvent (lower dielectric constants) favour E selectivity and a lower overall conversion. As shown in Table 1

• selectivity, but the high dielectric constant should favour Z selectivity. Compared to the original reaction (E:Z ratio 67:33, Table 1, entry 1), the reaction with excess benzaldehyde resulted in an increase in Z selectivity with an E:Z ratio of 52:48. Therefore, it can be concluded that, if a LAG solvent is

• LAG solvent (no work-up performed between the steps), a 98% conversion to stilbene was observed with an E:Z ratio of 43:57 (Scheme 4). As can be seen from the scheme, the reaction proceeded with high conversion and Z selectivity, which was ascribed to the high dielectric constant of ethanol. However

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• -workers proposed a variant of the defluorinative reaction using heteroatom nucleophiles using aluminum-based reagents such as Me2AlCl and (iPrO)2AlN3, and (Z) selectivity was observed for the formation of the monofluoroalkene [27]. When dimethylaluminum chloride was used, the resulting allylic chloride

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• much lower amount of (Z)-product (Scheme 4), implying that an ortho-relationship is optimum for the (Z)-selectivity. Interestingly, comparison of our initial results of the Takai olefination of 6 with entries 3 and 7 in Table 1, we can conclude that the presence of a Cl substituent in addition to the

• ortho-OH results in a higher (Z)-selectivity than for either substituent in isolation. In order to further investigate this cooperative effect, the (E):(Z)-product ratios were determined for various substituted salicylaldehydes (with ortho-OH substitution already demonstrated as optimum for favouring

• acetylated (14) and the relevant proton is therefore absent. This implies that increased acidity is not the primary factor at play. Instead, based on the higher (Z)-selectivity observed whenever the electron-withdrawing group was closer to the aldehyde moiety (Table 2), we propose that it is withdrawal of

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• -indolylmethanols through the hydrogen bond activating mode, which incorporated the 3-hydroxy-3-indolyloxindoles and o-hydroxystyrenes into the 3-allyl-3-indolyloxindoles, featuring one all-carbon stereogenic center and a (Z)-C=C bond. All products were obtained in excellent enantioselectivity (up to 97% ee) and (Z

• )-selectivity (up to >20/1 Z/E ratio, Scheme 52) [70]. Besides, the absolute configuration of the products can be controlled by the chiral CPA, selectively affording the (R)- or (S)-enantiomer based on the catalyst used. 3-Indolylmethanols have been recongnized as reactive precursors in organic synthesis for

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• % yield with Ir(ppy)3 as the catalyst [63]. In another report, MacMillan et al. showed that under similar photoredox conditions, 87 could couple with vinyl sulfone 90 to provide α-vinylation product 91 in 74% yield with excellent E/Z selectivity [65]. They also discovered that piperazine 87 could couple

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• on commercially available palladium on carbon (10 wt % Pd/C) [62]. The resulting bimetallic Ru–Pd heterogeneous catalyst 8-Pd/C exhibited the same activity in metathesis as catalyst deposited on activated carbon. Interestingly, the E/Z selectivity in reaction carried out with 8-C* was significantly

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• . Different strategies for the construction of E- or Z-cyclononenes have been reported to date and common reactions are summarized in Scheme 3. Transition metal-catalyzed ([M] = Ru, Mo, W) ring-closing metathesis (RCM) reactions of 1,10-dienes A can be employed for the synthesis of cyclononenes. The E/Z

• -selectivity of the olefin depends on the ring-size and the choice of catalyst. As a consequence of avoiding ring strain, small- and medium-sized rings are generally obtained with Z-configuration of the alkene. The Grob fragmentation reaction of fused 6,5-bicycles B is usually a concerted process that affords

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• are discussed. Surprisingly good yields of the ROCM products were obtained under neat conditions. Keywords: Grubbs’ catalysts; metathesis; ROCM; ROMP; Z-selectivity; Introduction Substituted tetrahydrofurans are a common motif found in many biologically active natural products [1][2], e.g

• , however, some electronic effects in 7-oxanorbornene should be also taken into consideration. Unexpectedly, the Z-selectivity predominated in most reactions catalyzed by [Ru]1 (see Table 1, entries 1–6, 10–15, and Table 2, entries 1–4). A two-fold excess of the Z isomer was observed in both groups of

• ROMP products prevailed. On the other hand the formation of polymeric products B may be suppressed by using the olefinic cross partner in excess and increasing concentration of reagents (the best results were obtained in the neat experiments). It should be noted that a different E/Z selectivity was

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• , delivering the hydrazines 3e–i in high yields (79–91%) and excellent E/Z selectivity, with an exception of the nitro-substituted 1g giving a moderate E/Z ratio (Table 2, entries 4–8). An ortho substituent on the benzene ring of the MBH alcohol was also well tolerated (Table 2, entry 5 vs 6). Notably, in

• , producing the corresponding α-alkylidene-β-hydrazino esters 3 in high yields (80–90%) and good E/Z selectivity (Table 2, entries 9–18). An exception was observed for the reaction of MBH alcohol 1j with tert-butyl azodicarboxylate (2c), which gave 55% yield and a modest E/Z ratio (5:1) (Table 2, entry 14

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• olefinating reagents) and 2) E/Z-selectivity of the reaction. Moriwake et al. noticed in their synthesis of vinylglycinol 64 that the reaction of methyltriphenylphosphonium bromide with KH as the base provided 62 in fairly good yield, but with complete racemization of the product (Scheme 25) [101]. This

• results, McKillop [27] noticed that with KHMDS as the base, there was no epimerization at all! To prepare “salt-free” ylides, it is necessary to remove lithium halide from the reaction solution. On the other hand KHMDS is a convenient base for the preparation of “salt-free” ylides. High Z-selectivity is a

• typical outcome with unstabilized ylides. Kim has investigated means of reversing the E/Z-selectivity to favour the E-isomer [104]. They noticed that olefination under the usual Wittig conditions provided high Z-selectivity (1:15 E/Z). When the reaction was quenched with MeOH at −78 °C, the E/Z-ratio was

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• decarboxylative fluoroalkylation (Table 1) [61]. A wide range of α,β-unsaturated carboxylic acids afforded the corresponding difluoromethylated alkenes in high yields and with excellent E/Z selectivity. The putative mechanism for this copper-catalyzed decarboxylative fluoro-alkylation involves the iodine–oxygen