(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• important synthons, which are widely used in agrochemicals, pharmaceuticals and other fields [24][25][26]. Fluoroorganic lithium and Grignard reagents have been obtained by the metalation reactions of organofluorine compounds containing bromine and iodine atoms with alkyllithium and Grignard reagents

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

• -catalyzed decarboxylative functionalizations employing RAEs have been established (Scheme 24). Baran and co-workers have reported arylation protocols (Scheme 24A) using arylzinc reagents [84][85], Grignard reagents [85] and arylboronic acids [86], as well as decarboxylative alkenylation [87] (Scheme 24B

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

• selectively transfer the acyl or acylthio moieties. Arylboronic acids 74 and amines 76 were suitable for the acyl transfer and led to ketones 78 and amides 80 as the desired products. While, Grignard reagents 75 and thiols 77 acted as soft nucleophiles and resulted in thioesters 79 and acyl disulfides 81

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• selective method for the synthesis of a wide range of organic compounds [55][56]. Organometallic reagents, such as organolithium, organomagnesium, and organozinc reagents are commonly used in conjugate addition reactions. 2.2.1 Reaction with Grignard reagents: Organomagnesium reagents, such as Grignard

• reagents, are commonly used in conjugate addition reactions. In the presence of Grignard reagents, the NHC-precursor salts do not require an addition of base as the Grignard reagent itself performs this role. In this way, Tomioka and co-workers [57] were able to achieve excellent regio- and

• enantioselectivity, using NHC–Cu(I) complexes generated in situ from chiral imidazolium salts containing possible chelating functional group(s). For example, the conjugate addition of Grignard reagents to 3-methyl- and 3-ethylcyclohexenones in the presence of the C2-symmetric chiral NHC–copper complex catalyst

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• construction of stereogenic centers using polar organometallics [1]. In this way, 1,4-additions of typical organometallics such as dialkylzinc, Grignard reagents, and trialkylaluminum have been developed [2][3][4][5][6][7][8][9]. Recently, also Cu-catalyzed conjugate additions of organozirconium [10][11] or

• of −7.13 eV and an even more negative NBO charge of −0.368 at the C-2 position. We can confer from these data that Zn enolates obtained from acylimidazoles are somewhat less reactive than silyl enol ethers obtained in the Lewis acid-promoted conjugate addition of Grignard reagents [23]. This finding

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• addition with Grignard reagents Feringa and co-workers realized the tandem conjugate addition of Grignard reagents to 4-chlorocrotonates 46 [42]. The enolate 47, which was formed in this process, underwent an intramolecular nucleophilic substitution to form cyclopropane derivatives. Thioesters, esters as

• well as ketones were compatible with this process. The chiral ligand L12 afforded the highest enantioselectivities of up to 98% ee (Scheme 12). Conjugate addition of Grignard reagents to coumarin (49) generated the corresponding magnesium enolates 50 [43]. In one instance, this enolate was trapped by

• conjugate additions of Grignard reagents. At the outset of our studies, there were works in which dialkylzinc additions were utilized to generate zinc enolates, and these enolates were then trapped with chiral sulfonylimines [24]. Specifically, we asked whether these magnesium enolates could be trapped with

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

• final ring-opened adduct 37. Copper-catalyzed reactions In 2009, Pineschi and co-workers explored the Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard reagents 48 (Scheme 8) [41]. The reaction is thought to proceed via the Lewis acid-catalyzed [3,4

• success of the reaction, hypothesizing it inhibited the classical [3,3]-sigmatropic Lewis acid-catalyzed rearrangement often observed. Both alkyl and aryl Grignard reagents were amenable to the reaction; however, heteroaryl Grignard reagents resulted in poor conversion. The Cu-catalyzed borylative

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• carbon–carbon iron-catalyzed cross coupling as a key step were developed, capitalizing on the low toxicity and the cheap cost of this abundant metal [10]. For instance, in 1971, Kochi developed an iron-catalyzed alkyl–alkenyl cross-coupling reaction between aliphatic Grignard reagents and vinyl bromides

• quest for suitable additives as surrogates of NMP. Szostak and Bisz reported in 2019 that N-methyl-ε-caprolactame (NMCPL) could be used as an alternative solvent, and sp3–sp2 cross-coupling reactions proceeding with good to excellent yields were reported. Alkyl Grignard reagents could thus be used in

• pheromones involving a key alkyl–alkenyl linkage introduction by iron-catalyzed cross-coupling reactions of α,ω-difunctionalized alkyl Grignard reagents with stereochemically pure dienyl phosphates were successfully performed at higher scales, in order to be successfully implemented in industrial processes

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• was not the case, the process was poorly reproducible. On the other hand, the 1,2-addition of Grignard reagents to 5 was observed, providing thus an alternative way of grafting a side chain. As summarized in Scheme 7a, this was envisaged through a sequence encompassing the 1,2-addition of the 1,3

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

• brine, dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography. Procedure for the addition of Grignard reagents to C3-silylated furfurals (preparation of compounds 5c, 6c, and 7c) In a flame-dried round-bottom flask under argon was placed the

• and Discussion Synthesis of 3-silylated 2-furyl carbinols C3-silylated furfurals 1a–c and 2c are accessible from furfural or 5-methylfurfural [20], respectively, according to our previously reported protocol for selective catalytic C3 silylation [15]. The addition of organolithium [21] or Grignard

• reagents [22][23] to these substrates was uneventful and allowed for the preparation of 2-furylalkyl (see 3a–c, 4c), -aryl (see 5c, 6c), and -allyl carbinols (see 7c) having furan rings with various triorganosilyl substituents at C3 in a synthetically useful yield and on an appropriate scale (Scheme 2

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• of aryl moieties into methylthio-substituted nitrogen heterocycles such as tCBz-mPYR are a Ni(0)-catalyzed cross-coupling reaction with Grignard reagents [34][36] or the Liebeskind–Srogl reaction employing arylboronic acids [37][38][39]. Taking into account a large assortment of arylboronic acids and

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

• first Fe-catalyzed cross-coupling reaction between Grignard reagents and vinyl halides [37]. As of late, the development of Fe-catalyzed cross-coupling methodology and mechanistic rationales have burgeoned [38]. Today, the rate of growth within the field of iron catalysis is much greater than that

• iron-catalyzed cross-coupling reactions of alkyl halides began in 2004 when Nakamura first reported the TMEDA-mediated Fe-catalyzed cross-coupling reaction between secondary bromides with aryl Grignard reagents [52]. Since then, several reports of alkyl halide cross-coupling reactions have been

• reported [53]. In 2015, Kang and co-workers described a FeCl2-catalyzed tandem cyclization/cross-coupling reaction of alkyl iodides 1 with aryl Grignard reagents 2 to give arylmethyl-substituted pyrrolidines and tetrahydrofurans 3 in poor to excellent yield (Scheme 3) [54]. The concept of alkyl halide

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• methodology based on the trans-stereoselective epoxidation reaction of 2,3-dihydroisoxazoles followed by the regioselective hydrolysis of the corresponding isoxazolidinyl epoxide [15][16]. Very recently, we have reported the synthesis of γ-(hydroxyamino)-α,β-diols by the addition of Grignard reagents to

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• Fe or Co catalyst and N-containing directing groups, while an excess of Grignard reagents was used [24][25]. Thereafter, they also reported the Cp*Co-catalyzed ortho-C–H alkenylation of ferrocenes with alkynes [26] and the mono- and di-selectivity could be controlled by the fine-tuned directing

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• -methoxybenzaldehyde imine derivatives with phenyl Grignard reagents as coupling partners. As the catalyst CrCl2 is used and either 2,3-dichlorobutane (DCB) or 1,2-dichloropropane (DCP) are used as oxidant to give 2,5-diarylbenzaldehyde after imine hydrolysis (Scheme 16B). Although benzaldehyde is a basic structure

• , it is present in compounds that have a significant anti-inflammatory activity (43 and 44) (Scheme 16A) [125]. The introduction of two distinct aryl moieties into arenes was also shown to be feasible through the sequential functionalization with two different Grignard reagents. For this purpose, the

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• to between 9–39%; a difluorinated byproduct was obtained when the substituent R was H (Scheme 6). Further applications were investigated by the same authors in 1984 [25]. Grignard reagents and enamines could be fluorinated, but in very low yields and unfortunately, this reagent was not so stable

• malonates and Grignard reagents were largely improved to up to 81% and 50%, respectively. The carbanions of aromatics, ketones, nitroalkanes, amides, etc. could also be reasonably well fluorinated and this study showed great progress. However, although these fluorinating agents were stable and easy-to

• reagents, a match process which minimizes side reactions. Thus, these N-fluoropyridinium salts made possible the fluorination of a diversity of nucleophilic organic compounds with different reactivities ranging across aromatics, carbanions (Grignard reagents, enolate anions), active methylene compounds

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• Re-face of the imine (Scheme 4) [1][36]. The nucleophilic addition reactions to N-tert-butanesulfinyl imines were also described by Ellman and co-workers who reported the addition of allylmagnesium bromide to ketimines. The employment of Grignard reagents showed greater diastereoselectivity than

• mechanism operating in reactions involving Grignard reagents in noncoordinating solvents, such as toluene and dichloromethane, while an acyclic model [43] is common in organolithium compounds in solvents such as THF. In the cyclic model, the bulky tert-butyl group occupies an equatorial position due to

• Grignard reagents to chiral aldimine (RS)-74, and an intramolecular oxidative cyclization of aminoalcohols derivatives 76, are key steps of this approach. Both diastereoisomers of aldimines 74 (RS and SS) were prepared from ᴅ-malic acid and the corresponding enantiomer of tert-butanesulfinamide

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• a multistep synthesis route. A first approach relied on the nucleophilic substitution of chlorine in cyanuric chloride with Grignard reagents, ammonia or amines [25][26], which suffered from the high reactivity of the Grignard reagents that prevents further functionalization. Moreover, this protocol

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

• this sense, while the addition of hard organometallic nucleophiles, such as lithium dialkylcuprates or Grignard reagents, failed, softer nucleophiles such as nitroalkanes cleanly added to the β-position, providing the Michael adduct 61. Unexpectedly, the conjugate addition reaction resulted in

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• Abstract Magnesium organometallic reagents occupy a central position in organic synthesis. The freshness of these compounds is the key for achieving a high conversion and reproducible results. Common methods for the synthesis of Grignard reagents from metallic magnesium present safety issues and exhibit a

• . Grignard reagents react with oxygen and water, yielding flammable gases and must be prepared, stored, and handled under an anhydrous inert atmosphere. Time-consuming titration is recommended but is unreliable as only the basicity is estimated. The freshness of these solutions is a key for achieving high

• conversion because the neutralization can alter the aggregation states, producing a significant batch-to-batch variability. The direct insertion of magnesium metal into organic halides is the most common method used to prepare Grignard reagents but present difficulties: (1) sluggish reactions with ordinary

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• of N-benzylidenemethylamine (40), shows the dependence of the imine yield on reaction time and temperature (Scheme 13). Higher yields of 40 were achieved at lower temperatures but longer reaction times were necessary in this case [85]. Di-tert-butyliminoxyl radicals react with Grignard reagents and

• employing organolithium reagents are presented below (Scheme 14). The Grignard reagents demonstrated very similar results that are omitted. Among the major C–O coupling product (oxime ether 42) small amounts of C–N coupling products (nitrones 43) were detected in the case of sterically unhindered

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• , and Grignard reagents. Review Copper-catalysed C–C bond-forming reactions at the heterocycle The direct synthesis of chiral heterocyclic molecules from pyridine, quinolone, or indole derivatives is advantageous due to the abundance of such building blocks. Unfortunately, establishing catalytic

• . In contrast, Grignard reagents are very favourable organometallics in terms of both their availability and atom efficiency. On the other hand, Grignard reagents are significantly more reactive than organoaluminium and organozinc reagents, rendering the catalytic control of both the regio- and

• enantioselectivity in addition reactions challenging. Nevertheless, Harutyunyan and co-workers introduced the first general catalytic methodology to access a wide variety of chiral piperidones in 2019, using Grignard reagents (Scheme 1C) [18]. Therein, a new catalytic system based on the ligand L4/Cu complex

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

• group [68] used silicon-based Grignard reagents 189 to add to conjugated heteroaromatics 188, e.g., benzoxazole (as an extension to more commonly studies ketones, esters, imines, etc.), leading to products 190–194. The heterocycle played a crucial role, as in its absence, none of the expected product

• . This same research group recently reported on the addition of silyl Grignard reagents to aziridines under copper catalysis [83]. While the use of RMgX led to high chemical yields of the desired products, the corresponding catalytic Cu/zinc reagents gave poor yields (ca. 20%; Scheme 45). A library of

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• the red phosphorus with 2-bromopyridine in potassium hydroxide/dimethyl sulfoxide emulsion, pyridylphosphine was obtained in moderate yields. Traces of phosphine oxide were present as evidenced by the observation of two phosphorus peaks in the 15P NMR spectrum. An optimized method via Grignard

• reagents has been reported by Kluver et al. [54], by which the product was isolated in excellent yield (71%). It was noted that the magnesium ions increase the water partition coefficient of these compounds since they coordinate stronger to the nitrogen atoms as compared to lithium ions. In this case