Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• one-pot, resulting in the generation of the stereochemically dense epoxyalcohol 37 in 68% overall yield. The treatment of compound 5 with EtMgBr as a Grignard reagent in the presence of CeCl3 gave the corresponding tertiary alcohol 38 with similar stereochemical features as of 36 in the formation of

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• added the double Grignard reagent 4 to methyl esters 5 [26]. A similar approach was established by Lavis, herein electrophiles (anhydrides or esters) were added to lithium or magnesium organyls 4 [27]. Johnsson and co-workers could establish dye formation by addition of aryllithium 7 to the silicon

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

• source and behaves as a nucleophile. The electrophile, such as an alkyl chain or an aryl ring with halides or sulfonates, reacts with the fluoride source (Scheme 1a). On the other hand, in the electrophilic fluorination, the nucleophile may be a carbon anion (e.g., Grignard reagent), a compound with

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

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

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• order to manipulate the NAD+ pathway in mammalian cells and tissues. The key step in the synthesis of the NMN analogues 39–41 is the activation of the 5′-hydroxy group of the NRH acetonide 42 with a Grignard reagent, to produce the corresponding magnesium alkoxide. As illustrated by the synthesis of the

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• DIBAL-H with benzylamine afforded the desired product 3 in 44% yield with 95% ee (Scheme 2, reaction 1) [52]. We then investigated the arylation of chiral cyclopropylamide 2f with Grignard reagent PhMgBr (Scheme 2, reaction 2). Only 37% of cyclopropyl ketone 4 were observed at room temperature with

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• Grignard reagent to add regioselectively to give 1,2-dihydropyrazine 3a. DFT calculations support the observations that the isolated regioisomer we obtained was the result of a thermodynamically favored 1,2-addition over a 1,6-addition [9]. It has also been shown that TMS-ketene acetals add selectively to

• conversion of 1,2-dihydropyrazines to Δ5-2-oxopiperazines, we decided to develop a one-pot approach towards their synthesis (Table 3). As described above, we first synthesized the phenyl-substituted 1,2-dihydropyrazine 4b by adding a phenyl Grignard reagent to benzyloxy-substituted N-acylpyrazinium salt in

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• that 13 had transferred its proton to the emerging, thermally stable [4] cleavage product 2K faster than to the residual PhCH2K (perhaps a problem of slow mixing). On the other hand, deprotonation of 13 by the Grignard reagent MeMgBr in THF was complete (quantitative CH4 evolution) within 20 min at 0

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• . Then, the cyclized product was subjected to the oxidation sequence with pyridinium chlorochromate (PCC) to generate cylophane derivative 115 in 75% yield (Scheme 17). Similarly, treatment of dialdehyde 113 with a freshly prepared Grignard reagent derived from 4-bromobut-1-ene (116) afforded dialkenyl

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• (12) in 94% yield using triphosgene, a standard reagent for the chlorination of phosphorus–hydrogen bonds [49]. Since a direct reaction with an excess of the Grignard reagent BrMg(CH2)6CH=CH2 would give 11, a dead end, initial conversion to the bis(borane) adduct 12·2BH3 was envisioned. However

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• at the less-hindered carbon of the unsymmetrical alkynes, which causes the high regioselectivity. Later, they proved that the hydroarylation reaction was also feasible with benzoxazoles 5 to form alkenated products 6 using CoBr2, bis[(2-diphenylphosphino)phenyl] ether (DPEphos), Grignard reagent, and

• . Based on the mechanistic studies, a possible reaction mechanism for the hydroarylation reaction was proposed in Scheme 9. The reaction begins with the generation of an ambiguous low-valent cobalt catalyst from the reaction of CoBr2, ligand and Grignard reagent, which gives the alkane and MgX2 as the by

• (Scheme 20b) [66]. Moreover, the Co-catalyzed hydroarylation of styrene with ketimine or aldimine proceeded without Grignard reagent using Mg metal as the reductant [67]. Recently, N–H imines 9d were also employed for the hydroarylation reaction with styrenes, giving a branched-selective hydroarylation

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds – an experimental and theoretical study

• Ana-Maria Preda,
• Małgorzata Krasowska,
• Lydia Wrobel,
• Philipp Kitschke,
• Phil C. Andrews,
• Jonathan G. MacLellan,
• Lutz Mertens,
• Marcus Korb,
• Tobias Rüffer,
• Heinrich Lang,
• Alexander A. Auer and
• Michael Mehring

Beilstein J. Org. Chem. 2018, 14, 2125–2145, doi:10.3762/bjoc.14.187

• ][47]. A more convenient synthetic route makes use of the Grignard reagent phenylmagnesium bromide and its reaction with bismuth trichloride [48]. Following this approach with slight modifications provides Ph3Bi with a yield of more than 80%. Crystallization from EtOH gave single crystals of the

• Wang et al. [52]. Compound 3 was obtained as colorless block-shaped crystals in yields of 83%. While our work was in progress, a crystal structure of 3 was reported by Gagnon et al. The authors confirmed the formation of 3 from the corresponding Grignard reagent and BiCl3 upon crystallization at 20 °C

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

• intermediate, 130, formed via the coordination of the Grignard reagent with ether was proposed to be operative in the reaction (Scheme 22). 2.2.4. Miscellaneous reactions: a. Halogenated benzo[7]annulenes and their synthetic potentials: In 1978, Föhlisch’s group reported the synthesis and ambident reactivity

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• demonstrated that the combination of a cobalt–N-heterocyclic carbene (NHC) catalyst and a Grignard reagent allows for the arene C–H functionalization with organic halides and pseudohalides under the assistance of nitrogen directing groups [17][22][23][24][25][26][27]. In this connection, Ackermann developed a

• cycle illustrated in Scheme 5. An alkylcobalt species A, generated from the cobalt precatalyst and the Grignard reagent, would undergo cyclometalation of magnesium alkylidene amide 1·MgX, generated from imine 1 and the Grignard reagent, to give a cobaltacycle species B while liberating an alkane R–H

• Grignard reagent would furnish the alkenylation product 3·MgX and regenerate the species A. While the relationship between the ligand and the catalytic activity remains unclear, we speculate that a strong σ-donating ability of NHC ligands would facilitate the SET step among others. Conclusion In summary

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• . The latter could be constructed through ring-closing metathesis of the corresponding precursor, e.g., 4,4,5,5-tetrafluoroocta-1,7-diene 5, using a Grubbs' catalyst. The octa-1,7-diene 5 could be obtained through a nucleophilic addition of a vinylic Grignard reagent to the γ-keto ester 6. Lastly, the γ

• , Scheme 2) and the results are summarized in Table 1. Thus, the treatment of 1.0 equiv of 7 with 2.0 equiv of 4-n-PrC6H4MgBr in THF at −78 °C overnight gave the corresponding γ-keto ester 6a in 85% isolated yield. Interestingly, although using an excess amount of Grignard reagent in this reaction, no

• adducts by over-reactions, e.g., A, B, C, etc. (Figure 2a), were observed. The suppression of the formation of the over-reacted products A–C may be brought about by the following possible reaction pathway (Figure 2b): (i) the nucleophilic attack of the Grignard reagent on the ester carbonyl functionality

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

• O-deprotection, N-Fmoc-protection and oxidation to the carboxylic acid afforded the final Fmoc-Ala-ψ[(Z)-CF=CH]-Gly (49). Then, it was discovered that the diastereoselectivity of the addition of the Grignard reagent on 47 was enhanced when dimethylzinc (Me2Zn) was used as an additive (Table 1) [39

• Grignard reagent to give 105. The last three steps (simultaneous deprotection of the amine and the alcohol in acidic conditions, Fmoc protection of the amine and oxidation of the alcohol into the corresponding carboxylic acid) led to the formation of three isosteres: Fmoc-Val-ψ[(E)-CF=C]-Pro (106a), Fmoc

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• organometallic reagents onto nucleoside aldehyde (Table 1), we decided to investigate the influence of the protecting groups of the uridine aldehyde on the stereochemical outcome of the nucleophilic addition of a Grignard reagent and we wish to report herein the results of our study. Results and Discussion We

• uracil (Table 2, entry 8) did not significantly change the 5’R/5’S ratio. In both cases, using 3.5 equivalents of Grignard reagent was required to complete the reaction. In order to improve this reverse diastereoselectivity, we envisaged the use of a more bulky protecting group, such as the

• diminished the yield to 55%. The bulkiness of the TIPS groups required the use of 5 equivalents of Grignard reagent to get a clean reaction and complete conversion of the starting material (Table 2, entry 14). The protection of the N-3 nitrogen with an allyl group was unfavorable and led to a 5’R/5’S 10:90

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• 4 under conditions used by us before, i.e., by treatment with isopropylmagnesium chloride, gave a mixture of diastereomers 7a and 7b. It was probably due to epimerization on carbon C2 of the carbanion, formed after attack of the Grignard reagent on sulfur. To our satisfaction, utilization of the

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• -less expensive DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), whose results are reported in this article in detail. Results and Discussion Preparation of substrates (E)-6 was carried out by way of our recently reported one-pot procedure [16]: thus, after reaction of an appropriate Grignard reagent and ethyl

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• receptor modulator, 3-[4-(1-piperidinoethoxy)phenyl]spiro[indene-1,1’-indane]-5,5’-diol hydrochloride (216) which may be used for a new treatment of hot flush [88]. In this synthesis, the reaction of 5-methoxyindan-1-one (212) with the Grignard reagent 217 followed by acid-catalyzed dehydration and

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• first case, the amount of oxidized Grignard reagent was significantly lower, showing the advantages of in-line measurements. In the in-line experiment the reaction mixture was introduced into the flow NMR cell at 1 mL min−1 showing a conversion of about 80% in 70 min. In this regard, Foley et al. [42

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• method A (61) but aliphatic nitriles are not converted to the desired product with method B. Trapping of radicals with method A led the authors to propose the electron transfer mechanism described in Scheme 21. The complex 62 reacts with the Grignard reagent to form the nickel-magnesium hydride

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• -addition of vinyl-MgBr followed by an aldol reaction (Scheme 6). The addition of a Grignard reagent to 17 was performed in THF at −45 °C in the presence of CuBr∙Me2S (0.5 equiv). After 15 min, a solution of aldehyde (either (R)- or (S)-10) in THF was added; the reaction mixture was warmed to −20 °C, and