gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• was to be evidenced by a substitution reaction at the alpha position. We started testing the different bases with lithium bis(trimethylsilyl)amide [39]. The reactions did not take place in the presence of LiHMDS (Table 1, entries 1 and 2), using either benzyl bromide or methyl iodide as electrophiles

• also tried to perform a substitution reaction by treating compounds 1a and 2a with tert-BuLi, employing methyl iodide as the electrophile. However, similar to previous reactions, this did not yield substitution products at the alpha position, but to the addition–elimination reaction products. More

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• ] heptyltriphenylphosphonium iodide (1.95 g, 4 mmol) was dissolved in dry THF (15 mL). A solution of n-butyllithium in hexane (1.6 M, 4.5 mL, 7 mmol) was added and the reaction mixture was stirred at 0 °C for 1 h. Methyl iodide (1.3 mL, 20 mmol) was added dropwise and the reaction mixture was stirred for a further 2 h. The

• solvent and excess methyl iodide were removed in vacuo. Analytical data were identical to those reported [31]. Methyl 4,6-dimethyldodec-5-enoate (6): Phosphonium salt 5 (185 mg, 0.4 mmol) was dissolved in dry, degassed THF (10 mL). LiHMDS in hexane (1 M, 0.6 mL, 0.6 mmol) was added slowly at −10 °C and

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• heteroaryls other than thiophene under standard conditions. Schreiner et al. established a further protocol for the one-pot synthesis of pyrazoles, where the alkynoyl moiety is generated by copper-catalyzed carboxylation of terminal alkynes followed by alkylation with methyl iodide, forming propiolic acid

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• adjacent to C5. A correlation to the acyl carbonyl carbon (C6) was not available at this stage. In order to obtain further information for connectivity, compound 1 was reacted with methyl iodide and K2CO3 to give a bismethylated derivative 1a. A methyl proton at δH 3.94 was of an N-methyl group (δC 38.5

• , 332.1832; found, 332.1838. Methylation of 1 Allostreptopyrrole A (1, 2.0 mg, 0.007 mmol) and K2CO3 (4.4 mg, 0.032 mmol) were stirred in dry DMF (0.5 mL) at 50 °C for 10 min. Methyl iodide (19 μL, 0.32 mmol) was added and the mixture was stirred at this temperature for 12 h [29]. Reaction completion was

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• -substituted indazole analogs in 44% and 40% yields, respectively, by treating compound 6 with methyl iodide and potassium carbonate in dimethylformamide (DMF) at room temperature for 17 h [40]. Other works have shown poor selectivity when 6 and other isomers similar to 6 were reacted with isopropyl iodide and

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• the exo-face. This process was used to prepare the known compounds 10a–c, and the novel materials 10d–f [9]. Thus, the reaction of o-dibromoxylene with cyrene gave the alcohol 10d in 71% yield over two-steps through the spirocyclic ketone 9d. Alkylation of 2 with methyl iodide gave an inseparable

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• methyl iodide yielding PA-CH3’, followed by ion exchange using an exchange resin to provide PA-CH3 as a yellow solid (74% yield over 2 steps; Figure 2a). Despite its large aromatic framework with a monocationic core, PA-CH3 was found to be soluble in water up to ≈0.9 mM. Using similar procedures

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

• 100 °C (oil bath) for 15 min. After cooling to room temperature, N-iodosuccinimide (3, 338 mg, 1.50 mmol) and DMSO (1.00 mL) were added and the mixture stirred at room temperature for a further 2 to 5 h (monitored by TLC). Then, methyl iodide (4a, 639 mg, 4.50 mmol) was added and the reaction mixture

• temperature, NIS (338 mg, 1.50 mmol) and 1.00 mL DMSO were added. After complete conversion (via TLC control), methyl iodide (639 mg, 4.50 mmol) was added and also stirred at room temperature for 5 min. Water was added to the mixture and the aqueous phase was extracted with dichloromethane. The combined

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• ) [107]. The synthesis starts from the lipid alcohol 19.1 which was deprotonated and alkylated with a mesylamine to produce 19.2. Then, the formation of the ammonium by reaction with methyl iodide followed by the deprotection of the benzyl protecting group under acidic conditions and the acetylation

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• methyl iodide (Scheme 5). Conclusion In conclusion, we have developed a semi-one-pot method for the synthesis of 2,3-annulated furans based on the Pictet–Spengler reaction. This method provides a shortcut to 4-substituted tetrahydrofuro[3,2-c]pyridines in reasonable yields starting from readily available

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• demonstrated by the formal total synthesis of (±)-6,7-secoagroclavine (Scheme 4) [108][109][110][111][112][113][114]. Towards this end, compound 11 was methylated efficiently and selectively at the secondary amide by treatment with methyl iodide in DMF to afford compound 13. In additional two steps

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• results, we started the photochemistry study of the considered pyrimidines from the corresponding methylated derivatives of 9. The products 10 were obtained by alkylation of compounds 9 with methyl iodide in DMF in the presence of K2CO3 (Scheme 4). At first, the photochemical behavior was investigated for

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

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ]. At 0 °C, attempts to generate the ‘ortho-lithiated’ dithiins resulted in quantitative ring opening, giving the dimethylated derivative 22 as the sole product (Scheme 6b). The lithiated 1,4-dithiins are also not stable at −70 °C in diethyl ether, and cannot be alkylated using methyl iodide. With a

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• undermethylated products regardless of the reaction time or the amount of methyl iodide added. In the literature [25], this problem is solved by using methyltriphenylphosphine bromide as a phase-transfer catalyst, and it has also worked in our reaction. Refluxing in NH4F methanol solution was chosen to cleave the

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• details). We also contemplated the use of alkyl iodides as electrophiles. Methylation with methyl iodide was efficient, as shown through the preparation of 28 in 61% yield from 4c. In contrast, higher alkyl iodides, such as ethyl iodide, failed to provide the alkylation product (i.e., 29) and only

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• ʟ-tryptophan (1) was much faster than with the tryptophan ester, taking only 45 minutes to complete. Interestingly, KMnO4 oxidation was selective, with no decarboxylation seen. Within 15 minutes, further treatment of 3a–e with methyl iodide in the presence of K2CO3 provided the corresponding methyl

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• diphenyl-N-benzyl-N-methylphosphinamide (107) in the presence of sec-butyllithium followed by treatment with methanol, deuterium oxide, methyl iodide, and benzaldehyde, affording a series of cyclohexadiene-fused γ-phosphinolactams 108–112 in low regio- and stereoselectivies (Scheme 21) [46]. They further

• intramolecular nucleophilic dearomatization and protonation or electrophilic alkylation reactions, affording the corresponding dihydronaphthylene-fused γ-phosphinolactams 135–142. Methanol was used as the electrophile for protonation, while methyl iodide and allyl bromide were used as electrophiles for

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• ) (TIPDS) protected uridine, protection of N3 was needed in order to prevent methylation at this position (Scheme 4). The N3-benzoylated derivative could then be treated with methyl iodide in the presence of silver oxide in order to methylate the 2'-OH. A similar strategy was employed to synthesize 3',5'-O

• -TIPDS-N4-benzoyl-2'-O-methylcytidine. Next, 3',5'-O-TIPDS-N6-benzoyladenosine suffered from methylation at the nucleobase and thus, 6-chloro-9-β-ᴅ-ribofuranosylpurine was instead used as the starting material. Once TIPDS protected, the 2'-OH could, once again, be selectively methylated with methyl

• iodide and silver oxide. The protected adenine base was regenerated by treatment with ammonia followed by benzoylation. Once the methyl group was incorporated into these ribonucleosides, the TIPDS group was selectively removed by tetrabutylammonium fluoride (TBAF) or hydrochloric acid treatment, followed

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• In conclusion, we have demonstrated an efficient synthesis of 2-substituted (alkyl, aminoalkyl) 4-aminophthalazinones 5 and 6 via the direct bromination of phthalazin-1(2H)-one (1) with potassium tribromide, followed by the alkylation of 4-bromophthalazinone 2 with methyl iodide, isopropyl iodide or

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• which was methylated using methyl iodide and lithium diisopropylamide (LDA) to produce (–)-81a in 84% yield. Desilylation of (–)-81a followed by tert-butyldimethylsilyl (TBS) protection of (–)-82a gave ester (+)-83. Compound (+)-83 was converted to (Z,Z)-(+)-84 by using iodination and a diimide

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• ) in 95% yield after 18 h (Scheme 12). Hydroxylamine (±)-104 was hydrolyzed in the presence of aqueous hydrochloric acid, and the resulting nitrone was heated in toluene to yield the homotropane (±)-105 in 57% yield over two steps. (±)-105 was alkylated with excess methyl iodide to form the

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• also obtained from 3m. S-Methylation of 3m was achieved in 91% yield with methyl iodide in the presence of NaH/THF and the S-benzylation has been carried out by a similar procedure (Scheme 5). To derive the mechanism of the reaction, a few control experiments have been executed (Scheme 6). Initially

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• ), sodium hydride (0.105 g, 4.2 mmol), and dried THF (16 mL). The mixture was stirred at rt for 2 h, and then methyl iodide (0.61 g, 4.3 mmol) was added and the mixture stirred at rt for 6 h. Then, distilled water (12 mL) and diethyl ether (15 mL) were added, the organic phase was separated, dried, and