Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• dibromide 3, produced by radical bromination of key intermediate 4. The principal challenge entailed in the envisaged synthesis was the construction of the bis(aryloxy)fluoromethane moiety of 4. The simplicity of this structure belies the paucity with which it is encountered in the literature, particularly

• undesired isomer were produced, recovery of unreacted 6 was simple and the quantity of 8 (<5%) was reduced compared to all previous attempts. Chromatographic separation permitted the removal of 8 and the isolation of a pure sample of compound 4. Synthesis of compound 1 Having produced the key intermediate 4

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• –elimination product 6b in good yield. These results provided crucial evidence for the mechanism of the reaction which suggested that β-sulfonyloxyenone could be the key intermediate in the formation of β-triazolylenone 3. Based on the above control experiments, the following mechanism is proposed. Initially

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ]pyridine and 2-amino-1,6-dimethylimidazo[4,5-b]pyridine) [23], and imidazo[4,5-c]quinoline (imiquimod) [24] based on the electrocyclization of 2-azahexatriene involving an isocyanate moiety as the key intermediate. In addition, we recently reported the total syntheses of marinoquinolines A (3a), B (3b

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• is described elsewhere [18]. Conversion of the cyano compound 7 into the corresponding amidine compound 1, the key intermediate, proved cumbersome. Several experiments and reagents [29] were tried before finding trimethylaluminum (Al(Me)3) and NH4Cl [30] as the reagents of choice for this conversion

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• of further C(7a)-hydroxylated bacterial pyrrolizidines and related molecules. Pyrrolizidine 14 (Scheme 1), the key intermediate in Snider’s improved route to jenamidine A and Bode’s preparation of pyrrolizixenamides A (9) and D (12), is formed by N-cyclization onto the nitrile group in cyano-β

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• (Scheme 23). The aldehyde (Z)-(+)-143a was the common intermediate for the synthesis of (E)- or (Z)-selective vinyl boronates or vinyl halides (+)-145 to accomplish total syntheses of all inthomycins A–C ((+)-1, (+)-2 and (–)-3, see Scheme 25 and Scheme 26). With the key intermediate (Z)-(+)-143a in hand

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• determine whether diethyl fluorophosphonate is a key intermediate in the reaction with aromatic alkynes. Based on a method by Gupta et al. [29], we obtained diethyl fluorophosphonate. Subsequently, the diethyl fluorophosphonate did not react with an aromatic alkyne in the desired phosphonofluorination so

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• ] cycloaddition produces tricycle 36 in the preparation of (±)-hirsutene (14) [24]. (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38 as a key intermediate to give angular-fused triquinane 41 [29]. (B) Synthesis of (−)-crinipellin A (15) [30]. (C) Synthesis of

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• desired pyrroles 4c–e in moderate to good yield. Notably, methyl 2-methyl-1-phenyl-1H-pyrrole-3-carboxylate (4c) is a key intermediate in the synthesis of a TRPM8 antagonist [43]. The substrate scope of the aromatic amine component was then examined, and the remarkable efficiency of our pyrrole synthesis

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• % yield (Scheme 1). Alkylation of 5 with 1,2-dibromoethane provided key intermediate azido-bromide 6 in 60% yield. This two-step route to 6 is efficient, but the 16% overall yield was lower than desired. An alternate route began by converting diol 4 to bis(2-hydroxyethoxy)naphthalene 7 in 92% yield by

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

• undergoes an addition reaction with a suitable nucleophile (Scheme 1). Importantly, the electrophilic mediated formation of this key intermediate 2 have been the cornerstone for allenamide chemistry over the past 15 years. Therefore, given the importance of the allenamide building block we sought a new

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• formed. The latter was indeed isolated as the main product (68% yield, Scheme 3). A plausible mechanism for the formation of the 2-aroylimidazoles 3/3' is depicted in Scheme 4. A key intermediate may be the in situ generated α-imino ketone 5. The latter is known to undergo dimerization to give 6 followed

• undergo a base-promoted loss of nitrogen to form α-imino ketones upon protonation [38]. A plausible mechanism for the formation of pyrimidine derivative 7a from 2a, in competition with imidazoles 3a/3a', is depicted in Scheme 5. The key intermediate 5a, formed by elimination of nitrogen from the enol

• very good yields (67–98%) when phenacyl azides are soluble in the eutectic mixture and is applicable to a range of substrates. Phenacyl azides, in turn, can also be competitively converted into 2,4-diaroyl-6-arylpyrimidines (45–88% yield) via an unprecedented cyclotrimerization reaction the key

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

• photoredox catalysis. This interception leads to a new metallic key intermediate 3 by single-electron transfer (SET). The desired coupling product 4 is then obtained after a reductive elimination (Figure 19). Applying such an approach paved the way towards unprecedented couplings benefiting from a SET

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• ], a bicyclic sesquiterpene that belongs to the cuparene family isolated from Thuja orientalis [76]. More specifically, the authors designed a simple route to enone 67, a key intermediate in several previous total syntheses [77][78]. Its synthesis was achieved in two steps, namely a nickel-catalyzed

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• irradiation, gives the intermediate species 39. The abstraction of a thiyl radical from the intermediate 39 yields the key intermediate dioxetane 40 and regenerates the disulfide. Finally, the reaction between the enol 33 and the dioxetane 40 affords benzaldehyde (41) and the product 42. In 2008, Tsuboi and

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• starting material was converted into bis(hydroxymethyl)quinolizidinone 56. After mesylation and the double displacement with sodium sulfide, spirothietane-quinolizidine 57 was obtained as a key intermediate. It was further applied in the total synthesis of four different natural products of Nuphar

• series of thietanose nucleosides 118 [53]. Similarly, enatiomeric thietanose nucleosides 123 were prepared from L-xylose [53] (Scheme 24). In 2010, Takahata and co-workers designed and synthesized thietane-fused nucleosides. They first prepared a key intermediate spiro acetal 125, which was converted

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• the protected ᴅ,ʟ-N-Boc-2-bromophenylalanine (89) using a Stille coupling reaction to give the o-vinyl derivative 90 as key intermediate. A hydroboration reaction of compound 90 afforded the primary alcohol 91, which was directly fluorinated and deprotected to give the free amino acids 93 (ᴅ and ʟ

Aryl-substituted acridanes as hosts for TADF-based OLEDs

• Naveen Masimukku,
• Dalius Gudeika,
• Oleksandr Bezvikonnyi,
• Ihor Syvorotka,
• Rasa Keruckiene,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 989–1000, doi:10.3762/bjoc.16.88

• prepared using simple synthetic procedures and characterized as hosts for TADF-based OLEDs. Results and Discussion Synthesis and characterization The synthetic routes for acridan derivatives 3–6 are outlined in Scheme 1. The key intermediate, 2,7-dibromo-9,9-dimethyl-9,10-dihydroacridine (1) was prepared

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• -phospholenium chlorides 3 was only postulated. Herein, two additional derivatives, the 4-methylphenyl- and ethyl-1-chloro-3-methyl-2-phospholenium chlorides 3c and 3h were isolated and characterized, which confirmed the key intermediate of the proposed mechanism. The chloro-2-phospholenium salts 3 were then

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• the cis-disubstituted double bond in the latter was performed under a high pressure of hydrogen, leading to the saturated tricyclic scaffold that was used as a key intermediate in the total synthesis of lycoflexine (15, Scheme 18). Manzamine alkaloids A highly interesting application of a metathesis

• the corresponding bicyclic dienic scaffolds. The subsequent hydroboration and aminohydroxylation carried out on these bicyclic dienes provided the AB subunit as a key intermediate component of manzamines A (16a) and E (16b, Scheme 19). Eventually, several highly elaborated transformations of the AB

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• resulted in 99% of the borylated product 414, which may indicate the presence of a radical intermediate in the second, protodeboronation step. Therefore, the key intermediate is the 1,4-adduct 415, which in the presence of base and water affords the saturated product (e.g., 410, 411; Scheme 66) [129]. The

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• the key intermediate aldehyde 25 (Scheme 4). Initially, we explored the Suzuki coupling reaction for substrate 4. Gratifyingly, the reaction product 24 was produced in 41% yield from our developed synthetic strategy. Then, compound 24 was subjected to an SeO2 oxidation reaction. The oxidation reaction

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• and the carbohelicene moieties (Scheme 1) [16]. The approach focused on the regioselective one-pot synthesis of a 7-hydroxybenzo[b]phosphole derivative from an 3-alkoxyphenylzinc reagent, an alkyne, and dichlorophenylphosphine [17]. The hydroxy group of this key intermediate served as a handle for the

• strong blue fluorescence in solution. The absorption and emission profiles of the π-extended phosphole oxide revealed their characteristics as hybrids of 2,3-dialkoxytriphenylene and 1-phenyl-2,3-dialkylbenzo[b]phosphole. We anticipate that the key intermediate of the present synthesis, 3, and related

• ) side view). UV–vis absorption (solid lines) and fluorescence (dashed lines) spectra of compounds 8a–c. Syntheses of PAH-fused phospholes featuring a 7-hydroxybenzo[b]phosphole as a key intermediate. Synthesis of phosphole-fused ortho-teraryl compounds 7. Oxidative cyclization of phosphole-fused ortho

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• catalytic strategy for the one-pot synthesis of N-sulfonylamidines is described. The cationic copper(I) complexes were found to be highly active and efficient under mild conditions in air and in the absence of solvent. A copper acetylide is proposed as key intermediate in this transformation. Keywords

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• arylcopper(I) species was the key intermediate. Terminal alkynes were also investigated under similar reaction conditions (Scheme 13) [37]. Aromatic and π-activated aliphatic substrates led to the desired products in moderate to very good yields. Moreover, vinyl sulfone derivatives were formed when the

• alkynes. The latter was also a key intermediate for the formation of α-trifluoromethylselenylated vinylsulfone. It is worth noting that the strategy for the trifluoromethylselenolation of boronic acid developed in our laboratory was applied in 2019 for the synthesis of the selenylated analog 30 of