Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• as a 1:1 mixture of diastereomers (Scheme 4). The same procedure was also applied to estrone to insert the spiro moiety at C-17 in 70% yield [14]. Spiro-β-lactam steroids A novel one-pot procedure to build spiro-β-lactams from enamides was described by Liu et al. The research group had previously

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• , enol ethers, and enamides, proved unproductive in generating the anti-Markovnikov product [90]. The authors attribute this outcome to the high stabilization of the corresponding cations from these substrates, rendering them unresponsive to nucleophilic attack by the chloride anion. Notably, neither the

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• reactivity of the C-centered radical with Ph-EBX (2). Aliphatic alkenes, enamides, enol ethers and acrylates were tested in the reaction but did not lead to formation of the desired products (Scheme S1, Supporting Information File 1). In almost all cases >70% of the EBX reagent was left after 16 hours of

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• . Intramolecular radical addition into the radical cation of the furan ring would then form cation 50 before nucleophilic capture by H2O leads to product 45. In 2020, the Wang group reported the functionalization of enamides employing radicals derived from NHPI esters in combination with indole nucleophiles [57

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• approach. Importantly, the demonstration of the exceptional compatibility between blue LEDs and diazirine compounds also held the promise of inspiring further exploration and development of novel synthetic strategies in this field. Enamides are commonly found in medicinal compounds and physiologically

• active natural products. The direct functionalization of C–H bonds in enamides offers a convenient and versatile approach to access a wide range of functionalized enamides. In 2021, Fu and his colleagues successfully developed a novel method for the stereoselective alkylation of enamides 14 using iodine

• efficient synthesis of diversely functionalized enamides 16 and 17, demonstrating remarkable tolerance towards various functional groups. In recent years, there has been a surge of research interest in coumarin derivatives due to their notable biological, pharmacological, and optical properties [16]. Zhou

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

• ]. This pathway involves the presence of methanesulfonic acid and a large amount of metal oxide to obtain the target product with moderate to good yield. In 2015, a MnO2-catalyzed sequential oxidative alkylation of C(sp3)–H/C(sp2)–H CDC and hydrolysis of enamides with ethers was reported by Xu et al

• cross-coupling of ethers with enamides. Ni(II)-catalyzed CDC of indoles with 1,4-dioxane. Chemo- and regioselective ortho- or para-alkylation of pyridines. Asymmetric CDC of 3,6-dihydro-2H-pyrans with aldehydes. CDC of heterocyclic aromatics with ethers. Indium-catalyzed alkylation of DHPs with 1,3

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

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• -diaryl-substituted enamides is observed. Thus, the method provides synthetic access to both isomers of the target enamides from (Z)-β-enamido triflates. Keywords: enamides; isomerization; Suzuki–Miyaura coupling; vinyl triflates; Introduction Enamides are substrates of high value in organic synthesis

• of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or

• isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri- and tetrasubstituted enamides. Recently, we have reported a triflic acid-mediated reaction of N-fluoroalkyl-1,2,3-triazoles leading to (Z)-β-enamido triflates [21] and Lewis acid-mediated reaction

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

• disubstituted alkene 13 in refluxing diglyme or triglyme at 190 °C (Scheme 7) [23]. The method has been widely used for the difluorocyclopropanation of allylic alcohol derivatives [24], steroids [25], and N-Boc-protected enamides [26]. Boron-substituted difluorocyclopropanes 16 can be also obtained from 12

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• separately developed a Minisci-type reaction using phthalimide esters 123; however, their system did not extend past isoquinoline substrates 124 (Scheme 17b) [62]. Zheng and Studer expanded the scope of this type of reactivity to a three-component cascade reaction with alkyl bromides 125 and enamides 126

• tautomer 147, and the CPA-catalysed Povarov reaction between them gives the enantioenriched THQ 144 in good yields and enantioselectivities (4 examples, up to 97:3 er). This reactivity has been extended to enamides 148, with the imine generated from the α-amino acid 149 now reacting with 148 in a CPA

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• analogous enamides [57], the facile [2 + 2] photocycloaddition process likely occurred due to favorable orientation of the interacting molecules and close contacts between alkene carbon atoms in the crystal structure. Consequently, the synthesis of product 5c was performed in darkness. N1-Styryl-substituted

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• radical cyclization of allenamides have been reported by Hsung and co-workers, where the radical adds principally to the central carbon of the allene (10) [45]; and (iii) the photoredox-catalyzed addition of radicals to enamides reported by Masson [46][47][48][49], and more recently by our own laboratory

• conjugated N-acyliminium 14. The iminium 14 could then undergo traditional nucleophilic addition giving the addition product. Given that the iridium complex Ir[(ppy)2(dtbbpy)]PF6 had been effective [47][48][50] in this radical/cationic pathway with enamides we would now like to report our preliminary

• -acyliminium intermediate is provided to explain the addition product distribution. Results and Discussion We began our study by using the iridium catalyst Ir[(ppy)2(dtbbpy)]PF6 (17) and the reaction conditions used in the addition of amine nucleophiles to enamides [48][50]. By exploiting these reaction

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• ) intermediate occurs prior to the one-electron oxidation by the photoexcited catalyst. This contribution inspired also other research groups to investigate synergistic catalyses using Pd-based C–H catalysts. In 2016, Lei’s group reported the aerobic intramolecular oxidative carbonylation of enamides for the

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

• the same year, Loh’s group [132] used the same copper catalyst and Togni’s reagent to achieve the trifluoromethylation of enamides in good yields at room temperature (Scheme 72a). Meanwhile, this reaction exhibited excellent stereoselectivity towards the E-isomer. One year later, the same group [133

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

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• obtained β-ketoenamides are alkenes with a remarkable assembly of functional groups: they are enamides, enol ethers and α,β-unsaturated carbonyl compounds at the same time. In addition, their methyl ketone subunit is required for some of the subsequent transformations, e.g., the synthesis of pyridin-4-ols

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• work by Arisawa et al. [75], who reported a synthesis of indoles by RCM of sterically less encumbered enamides, we investigated the RCM of 20. Unfortunately, no conversion to the indole 22 could be observed under various conditions. Ring-closing metathesis of 19 was, in contrast, successful and

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• the catalyst thereby leading to the expected products 41 with yields in the 26–75% range (Scheme 13) [48]. Interestingly, an alkene diazidation reaction is observed by simply performing the transformation in DMSO and replacing Cu(OTf)2 by CuI as the catalyst. Enamides 42 are also relevant substrates

• for the 1,2-benzoyloxy-azidation reaction. Based on a preliminary observation made during their study on catalytic trifluoromethylation of enamides [49], the group of Gillaizeau has reported the catalytic conversion of enamides with various ABX derivatives 44 [50]. A screening of various metal

• . Catalytic asymmetric benzoyloxy-alkynylation of diazo compounds. Catalytic 1,2-benzoyloxy-azidation of alkenes. Catalytic 1,2-benzoyloxy-azidation of enamides. Catalytic 1,2-benzoyloxy-iodination of alkenes. Seminal study with cyclic diaryl-λ3-iodane. Synthesis of alkylidenefluorenes from cyclic diaryl-λ3

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• is well documented that Togni reagents can realize the direct trifluoromethylation of alkenes [58][59][60] and electron-rich enamides [61]. Inspired by this, we envisaged that Togni reagent 1 could also enable the introduction of a CF3 group to the β-position of enamine substrates, and the so

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• , azidobenziodoxolones 36b (ABX), could be utilized for atom-economical reactions. Gillaizeau and co-workers developed an iron-catalysed oxyazidation of enamides 45 using ABX derivatives 36b (Scheme 24) [58]. The reaction proceeds with complete regio- and stereoselectivity introducing the azide group in C2 and the ester

• . Oxyalkynylation of diazo compounds 42. Enantioselective oxyalkynylation of diazo compounds 42’. Iron-catalysed oxyazidation of enamides 45. Acknowledgements A.B. is thankful for a scholarship from the Fonds der Chemischen Industrie. P.F. is thankful for a postdoctoral scholarship from the German Academic

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• our previous study on the bromination of enamides [11]. Thus, using a slight excess of DIB along with a two-fold amount of lithium bromide at 0 °C in dry acetonitrile rapidly yielded dibromo adduct 2a in 91% yield (Table 1, entry 1). Switching the reaction conditions to bromo(trifluoro)acetoxylation

• case the analogous bromoethoxylated adduct 4a’ could be isolated in 68% yield, albeit along with 25% of 2a (Table 1, entry 6). Turning our attention to iodination, we first used the combination of PIFA and KI that had given the best results with enamides [13]. Thus, iodo(trifluoro)acetoxylated adduct

• did isolate dibromo adduct 2a but only with 47% yield and we also observed the formation of various byproducts such as ene-bromination adduct 6a’ (Scheme 7b) [27]. Moreover, for the iodination of enamides using the PIFA/KI combination we had already shown that the observed reactivity is more akin to

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• sodium sulfinates and enamides, applying Rose Bengal as photocatalyst and nitrobenzene as terminal oxidant (Scheme 43) [80]. In general, this procedure is suitable for the cross-coupling of a variety of substituted secondary enamides with alkyl, aryl and heteroaryl sodium sulfinate salts. Tertiary

• enamides could not be reacted with sodium sulfinates to yield the respective products. Wang and co-workers described a new method for the cyclization of phenyl propiolates with sulfinic acids, generating valuable coumarin derivatives in 2015 (Scheme 44) [81]. Visible-light irradiation of Eosin Y allows the

• ]. Two examples, norbonene and styrene, were presented and [Ru(bpy)3]Cl2 was used as photoredox catalyst. The groups of Zhang and Yu reported two additional photoredox-catalyzed methods for the sulfonylation of olefins. In their first paper they applied enamides as olefins, which were sulfonylated to the

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• reaction, in classical solvents or in an ionic liquid media, to yield the corresponding CF3 alkenes (Scheme 28) [35][36]. As for Yu, Zhang and co-workers, they described the trifluoromethylation of two enamides under photocatalytic conditions, using similar conditions as those they proposed for the

• trifluoromethylation of (hetero)arenes under photoredox catalysis. Direct C–H trifluoromethylation of five- and six-membered ring (hetero)arenes using heterogeneous catalysis. Trifluoromethylation of terminal olefins. Trifluoromethylation of enamides. (E)-Selective trifluoromethylation of β-nitroalkenes under