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

• oxazolidinone-substituted ynamide also proved to undergo iodo(III)azolation in a regio- and stereoselective fashion to give the product 4ai in a moderate yield. Note that terminal alkynes such as phenylacetylene also took part in the reaction, albeit in a much-diminished yield (7% by 1H NMR; data not shown

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• the potential NHC precursor to A, a polysubstituted 3-aminoimidazo[5,1-b]oxazol-6-ium motif B, might be rapidly accessed from an ynamide by sequential oxazole-forming annulation and imidazolium formation steps. The basis of this approach was a gold-catalysed oxazole formation developed in our group

• incorporating the unsaturated oxazole counterparts has not been explored. Results and Discussion Reaction of ynamide 1a with the N-acylpyridinium-N-aminide reagent 2 proceeded in good yield to afford oxazole 3 bearing a C-2 methyleneamino moiety as the first example of a free secondary amine in this annulation

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

• agent for TCNE. Anthracene-based ynamide 16 offers two potential reactive sites for TCNE, one residing at the anthracene moiety and other at the alkyne moiety, as shown in Scheme 9 [71]. As exemplified by Trolez et al., the introduction of one equivalent of TCNE to 16 at room temperature initiates a [4

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

• sulfenylation of yne-tethered ynamide 147 with N-thiosuccinimides 1 was possible in the presence of only methanesulfonic acid in dichloromethane at room temperature (Scheme 63) [93]. The electrophilic activation of propargylalkyne 147 generated in situ a sulfonium cation 1-I. Afterwards, 6-endo-dig cyclization

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

• 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

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• Beckmann reaction of oximes with p-toluenesulfonyl azide [34], the sulfonyl ynamide rearrangement by treatment with amines [35], the sodium iodide catalyzed reaction of sulfonamide with formamide [36], and the condensation of sulfonamide derivatives with DMF–DMA [37]. A few representatives of N-sulfonyl

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• of acetylenic ethers gave α-halovinyl ethers [38]. HBr generated in situ from BTMS and water was also used in the synthesis of α-bromoenamides from an ynamide [39]. However, to the best of our knowledge, there are no reports on the formation of oxazoles in this manner [40]. We found that the addition

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• use of an inexpensive catalyst, simple reaction conditions, simple work-up without column chromatographic purification for most of products and high yields. Keywords: [3 + 2] cycloaddition; isoxazole; pyrrole; silver catalysis; ynamide; Introduction Silver-catalyzed transformations of alkynes have

• reported [42]. Results and Discussion An initial experiment was carried out with ynamide 4a and isoxazole 5 as the selected substrates based on the known procedure developed by Ye’s group [31]. With pyrrole 6, a 42% yield was obtained using AgNTf2 (5 mol %) catalyst and DCE as the solvent at 80 °C for 2 h

• (Scheme 3). The reaction conditions were then further optimized but without obvious improvement of the yield. We presumed the reason might be due to the low nucleophilic reactivity of isoxazole 5 to the ynamide motif by silver activation. Therefore, we considered that the introduction of an amine motif

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

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• the isocyanide component acts as a one-carbon center, in this reaction the ynamide compound has a two-carbon center role. As shown in Scheme 12, the reaction of dehydrocholic acid (36), an amine and an aldehyde with the key ynamide component provided a new type of pseudo-peptidic steroid 37, obtained

• of a Lewis acid like BF3·Et2O for a suitable activation of the imine. Based on the same idea of exploiting the reactivity of ynamides, Cui’s group developed a 3CR wherein an o-hydroxy-benzhydryl alcohol was used in place of the aldehyde or imine components upon reaction with ynamide and a carboxylic

• with an alkynyl seco-cholestane [34]. Multicomponent synthesis of steroid–thiazole hybrids from a steroidal ketone [36]. Synthesis of cholanic pseudo-peptide derivatives by novel MCRs based on the reactivity of ynamide [37][38]. Synthesis of steroid-fused pyrimidines and pyrimidones using the Biginelli

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• conjugate addition of benzamide nitrogen onto the 2-ynamide generates the final cyclization product 24 through allene intermediate 28. Taking into account that the reaction does not take place with internal alkynes, the authors conclude that a terminal alkyne is necessary for the formation of the first

Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides

• Armando Navarro-Vázquez

Beilstein J. Org. Chem. 2015, 11, 1441–1446, doi:10.3762/bjoc.11.156

• predict the experimentally observed behavior for several examples from the literature. Keywords: allenamide; DFT; isomerization; ynamide; Introduction Allenamides [1][2] and ynamides [3][4][5] have become useful functional groups for organic chemistry synthesis in the last years. Reduced electron pair

• Hsung and coworkers, “…This poses an interesting fundamental question as to why the thermodynamically more stable ynamide … was not found if these isomerizations involved an equilibration mechanism…” [2]. The available experimental data strongly suggest that allenamides do not always convert to ynamides

• due to thermodynamic rather than kinetic reasons, and it is not necessarily the case that ynamides are more stable than the parent allenamides. Here it is hypothesized that N-propargylamide ↔ allenamide ↔ ynamide interconversion takes place reversibly and the outcome of the reaction is related to the

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• alkenes is the carbometallation reaction of alkynes [16][17][18], ynamide should be a suitable substrate for the regio- and stereoselective synthesis of enamide through carbometallation reaction [19][20][21][22]. Although the stereoselectivity of the carbocupration is usually controlled through a syn

• the carbocupration of an N-alkynylsulfonamide could be easily achieved, we were interested to see whether such a carbocupration reaction could be extended to ynamide 4 bearing an acyclic carbamate moiety. We were pleased to find that this reaction could also be performed on N-alkynylcarbamate 4 with

•  3. Our initial attempt was performed with organocopper species prepared from alkylmagnesium halide and CuBr (1:1 ratio) and ynamide 7a (R1 = Hex), which cleanly led to the enamide 9a in very good isolated yield for the addition of MeCu, and with excellent regioselectivities (α/β > 95:5, Table 3

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• -catalyzed carbozincation of alkynyl sulfoximines. Scope of rhodium-catalyzed carbozincation of ynamide. Sequential I/Mg/Zn exchange and arylzincation of cyclopropenes. Manganese-catalyzed arylmagnesiation of arylacetylenes. Acceleration effect of additive on chromium-catalyzed arylmagnesiation

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• formal synthesis of the anti-dyskinesia agent sarizotan. Results and Discussion Feasibility of the deprotonation/intramolecular carbolithiation To first evaluate the compatibility of the ynamide moiety with the lithiation step and address potential problems associated with competitive carbolithiation of

• the activated alkyne, we first reacted N-benzyl-ynamide 7 with one equivalent of sec-butyllithium and tetramethylethylenediamine (TMEDA) in THF at −78 °C for 15 minutes, followed by the addition of methyl iodide. The corresponding N-phenylethyl-ynamide 8 was obtained in nearly quantitative yield

• , therefore demonstrating the compatibility of the ynamide group with the deprotonation step (Scheme 2a), although longer reaction times before the addition of methyl iodide resulted in much lower yields and extensive degradation: The intramolecular carbolithiation of N-allyl-ynamides to 1,4-dihydropyridines

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• (branched/linear: 82/18), again showing that the chelation effect plays a major role in the regiochemistry of the carbometalation. The carbometalation of enantiomerically enriched cyclic ynamide 20 was recently used in a single-pot operation as a new entry to aldol products 21 possessing quaternary

• stereocenters (Scheme 10) [23]. Sulfonyl-substituted ynamide 22 has also been investigated in carbocupration and copper-catalyzed carbomagnesiation reactions (Scheme 11) [22]. Irrespective of the conditions, the carbometalation reaction on sulfonyl-substituted ynamide 22 is slower than that with ynamide 17. In

• α-alkoxyalkynes. Carbocupration of substituted α-alkoxyalkynes. Formation of the branched isomer. Formation of the linear isomer. Carbocupration of O-alkynyl carbamates. Carbocupration of ynamines. Carbocupration of ynamide. Formation of aldol products possessing stereogenic quaternary carbon