Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions

• Kendra Leahy Denlinger,
• Lianna Ortiz-Trankina,
• Preston Carr,
• Kingsley Benson,
• Daniel C. Waddell and
• James Mack

Beilstein J. Org. Chem. 2018, 14, 688–696, doi:10.3762/bjoc.14.57

• the Wittig reaction. Keywords: green chemistry; high-speed ball milling; HSBM; LAG; liquid-assisted grinding; Wittig; Introduction Mechanochemistry is maturing as a discipline and continuing to develop and grow [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Thus it is important to continue

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• Resch PM10 planet ball mill equipped with metal balls (d = 8 mm, 500 rpm, 10 min milling time) was used for dry milling of powdered Ce0.495Sn0.495Pd0.01O2–δ and wet milling (suspension in water) of Ce0.20Sn0.79Pd0.01O2–δ, respectively. These two catalysts were chosen since they showed the highest

• activities for Suzuki–Miyaura couplings in batch [37] and continuous flow [38]. After milling, the coarse and fine fractions of the particles were separated via sedimentation. For this purpose, 2 g of catalyst were suspended in 1 L water, the particles were de-aggregated by ultrasonic treatment and left to

• the Pickering emulsions for multistep reactions as well as on the proposed procedure for the synthesis of valsartan and sacubitril. Targeted integrated multistep synthesis of valsartan (1) and sacubitril (2). Particle size distribution of Ce0.495Sn0.495Pd0.01O2–δ after size reduction via milling and

Palladium-catalyzed ortho-halogenations of acetanilides with N-halosuccinimides via direct sp² C–H bond activation in ball mills

• Zi Liu,
• Hui Xu and
• Guan-Wu Wang

Beilstein J. Org. Chem. 2018, 14, 430–435, doi:10.3762/bjoc.14.31

• . China 10.3762/bjoc.14.31 Abstract A solvent-free palladium-catalyzed ortho-iodination of acetanilides using N-iodosuccinimide as the iodine source has been developed under ball-milling conditions. This present method avoids the use of hazardous organic solvents, high reaction temperature, and long

• corresponding N-halosuccinimides. Keywords: acetanilide; ball milling; C–H activation; halogenation; mechanochemistry; N-halosuccinimide; palladium catalysis; Introduction Aryl halides have been widely utilized in organic syntheses, which give access to a range of complex natural products [1][2]. However

• ], we have independently investigated the solvent-free ortho-iodination of acetanilides under ball-milling conditions [45]. In addition, the current reaction can be extended to ortho-bromination and ortho-chlorination by using the corresponding N-halosuccinimides. Herein, we report these regioselective

Mechanochemistry

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 2372–2373, doi:10.3762/bjoc.13.234

• otherwise impossible chemical reactivity in many cases. From a green chemistry perspective, mechanochemical activation conducted by milling, shearing, pulling or ultrasonic irradiation allows for the possibility to drastically reduce the amount of solvent needed during chemical reactions, even to the point

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• reactions using Cu(II), Cu(I) and Cu(0) catalysts have been successfully implemented to provide novel 6-phenyl-2-(trifluoromethyl)quinolines with a phenyl-1,2,3-triazole moiety at O-4 of the quinoline core. Milling procedures proved to be significantly more efficient than the corresponding solution

• reactions, with up to a 15-fold gain in yield. Efficiency of both solution and milling procedures depended on the p-substituent in the azide reactant, resulting in H < Cl < Br < I reactivity bias. Solid-state catalysis using Cu(II) and Cu(I) catalysts entailed the direct involvement of the copper species in

• the reaction and generation of highly luminescent compounds which hindered in situ monitoring by Raman spectroscopy. However, in situ monitoring of the milling processes was enabled by using Cu(0) catalysts in the form of brass milling media which offered a direct insight into the reaction pathway of

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• , France Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France 10.3762/bjoc.13.217 Abstract Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution

• and Discussion First we studied the preparation of simple Pro–Pro DKP as a model compound. The use of ball milling in peptide synthesis has drawn some attention in the recent years [20][21][22][23][24][25][26][27][28]. We took advantage of our extensive experience in peptide mechanosynthesis [20][23

• -3-(3-dimethylaminopropyl)carbodiimide (EDC), ethyl cyano(hydroxyimino)acetate (oxyma) in the presence of a base and a liquid additive, were adapted to the preparation of Z–Pro–Pro–OMe (7) and Boc–Pro–Pro–OMe (8, Table 1). It consisted in ball milling the two amino acid derivatives 5 or 6 with 2 in

The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy

• Patrick A. Julien,
• Ivani Malvestiti and
• Tomislav Friščić

Beilstein J. Org. Chem. 2017, 13, 2160–2168, doi:10.3762/bjoc.13.216

• milling frequency on the course of a mechanochemical organic reaction conducted using a vibratory shaker (mixer) ball mill. The use of in situ Raman spectroscopy for real-time monitoring of the mechanochemical synthesis of a 2,3-diphenylquinoxaline derivative revealed a pronounced dependence of chemical

• reactivity on small variations in milling frequency. In particular, in situ measurements revealed the establishment of two different regimes of reaction kinetics at different frequencies, providing tentative insight into processes of mechanical activation in organic mechanochemical synthesis. Keywords

• : green chemistry; mechanism; mechanochemistry; milling; monitoring; Raman spectroscopy; Introduction Over the past decade, mechanochemical reactions [1][2][3][4], i.e., chemical transformations induced or sustained through the application of mechanical force in the form of grinding, milling and shearing

Correction: Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 2128–2130, doi:10.3762/bjoc.13.210

• . Universidad 1001, Cuernavaca, Morelos, 62210, Mexico El Colegio Nacional, Luis Gonzáles Obregón 23, Centro Histórico, Ciudad de México, 06020, Mexico 10.3762/bjoc.13.210 Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic resolution; mechanochemistry; The original published Tables

• under ball milling. Substrate scope for the enzymatic resolution of N-benzylated-β3-amino esters. Recycling capacity of immobilized CALB under HSBM conditions. Scaling-up of the enzymatic hydrolysis reaction under ball-milling using substrate rac-1a. Supporting Information Supporting Information File

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• Abstract While presenting particularly interesting advantages, peptide synthesis by ball-milling was never compared to the two traditional strategies, namely peptide syntheses in solution and on solid support (solid-phase peptide synthesis, SPPS). In this study, the challenging VVIA tetrapeptide was

• synthesized by ball-milling, in solution, and on solid support. The three strategies were then compared in terms of yield, purity, reaction time and environmental impact. The results obtained enabled to draw some strengths and weaknesses of each strategy, and to foresee what will have to be implemented to

• ][17]. While these approaches enable to circumvent the use of toxic solvents and bases [18][19][20], no comparison between ball-milling and conventional approaches was performed, discussed and communicated. Therefore, we performed this comparison by applying three different peptide synthesis strategies

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• group compounds and frameworks. Keywords: ball milling; main group; mechanochemical synthesis; mechanochemistry; Introduction The original mainspring for the current expansion of solid state methodologies is the need for cleaner, safer and sustainable chemical transformations – particularly since raw

• chemist. Mechanochemistry is defined as the field of reactions caused by mechanochemical forces (e.g., compression, shear or friction) [18][19]. Examples of mechanochemical methods are manual and ball-milling grinding techniques [20][21][22]. Traditional manual mortar and pestle grinding methods are

• susceptible to variable factors, both human and environmental [23]. In contrast, modern milling technologies address these issues through the use of enclosed solvent-free reaction environments and well-defined experimental conditions throughout the mechanochemical process [24][25]. Amongst the commercially

Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient air: Revisiting TEMPO-assisted oxidations

• Andrea Porcheddu,
• Evelina Colacino,
• Giancarlo Cravotto,
• Francesco Delogu and
• Lidia De Luca

Beilstein J. Org. Chem. 2017, 13, 2049–2055, doi:10.3762/bjoc.13.202

• primary and secondary alcohols to the corresponding aldehydes and ketones by mechanical processing under air. Ball milling was shown to promote the quantitative conversion of a broad set of alcohols into carbonyl compounds with no trace of an over-oxidation to carboxylic acids. The mechanochemical

• reaction exhibited higher yields and rates than the classical, homogeneous, TEMPO-based oxidation. Keywords: aldehydes; ball milling; ketones; mechanochemistry; oxidation reactions; TEMPO; Introduction Aldehydes and ketones constitute some of the most powerful and versatile building blocks that are

• aims to provide alternative methods to traditional syntheses in organic and inorganic chemistry [49][60][61]. Mechanochemistry is also used in supramolecular chemistry [62] and metal-organic chemistry [63]. In this work, we show that mechanical processing by ball milling can represent a viable solution

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• .13.197 Abstract The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction

• leads to a quantitative conversion to p-nitrobenzylidenemalononitrile within 50 minutes. The in situ data indicate that the process is fast and proceeds under a direct conversion. After stopping the milling process, the reaction continues until complete conversion. The continuous and the stopped milling

• process both result in crystalline products suitable for single crystal X-ray diffraction. Keywords: ball milling; C–C coupling; in situ; Knoevenagel condensation; mechanochemistry; Introduction Mechanochemical syntheses have gained increasing popularity in different areas such as materials science

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• sources and iron precursors were applied to develop new bio-nanocomposites by mechanochemical milling processes. The proposed methodology was demonstrated to be advantageous in comparison with other protocols for the synthesis of iron oxide based nanostructures. Additionally, mechanochemistry has enormous

• atmosphere. The Fe2O3-PS4-MNP catalyst was obtained using 2 g of polysaccharide S4, 4 g of Fe(NO3)3·9H2O and 1.5 mL of propionic acid. The milling process was carried out at 350 rpm for 15 and 30 min, respectively. The resulting material was oven-dried at 100 °C for 24 h and slowly heated up (1 °C/min) to

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• the functionalization of premade polymers. Recently, Yan and co-workers used ball milling to deacetylate chitin to afford chitosan [30]. We now provide a proof-of-principle demonstration of mechanochemical ω-functionalization of α-protected methoxy-PEG (mPEG) with –COOH, –OTs, –NH2, –Br, and –SH

• ball-milling. Namely, the tosyl moieties are known as excellent leaving groups, making tosylated mPEG (mPEGx–OTs) useful synthons for accessing further PEG derivatives. For this, we conducted a two-step one-pot reaction involving milling first the mPEG reactant with a base, followed by addition of p

• -toluenesulfonyl chloride (TsCl) and further milling (Scheme 1a, Table 1). mPEG750 was used to survey and optimize the tosylation reaction conditions. Milling of only mPEG with TsCl led to a poor conversion of 6% (Table 1, entry 1). However, addition of 1 equivalent of weak base, such as K2CO3 or N,N

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• -iodoketones (2 molecules), prepared in situ from aryl ketones, was performed efficiently under mechanochemical conditions involving high-speed vibration milling with a single zirconium oxide ball. This reaction afforded symmetrical frameworks containing two pyrrole or fused pyrrole units joined by a spacer

• vibration milling (HSVM) [14][15]. The importance of pyrrole frameworks stems from the status of this heterocycle as a privileged structure in drug discovery due to its presence as a structural core in molecules that are able to bind various receptors [16]. Results and Discussion Our route to the target

• bispyrrole systems is summarized in Scheme 2. Treatment of aromatic ketones 4 with N-iodosuccinimide (NIS) in the presence of toluenesulfonic acid under high-speed vibration milling for 1 h afforded α-iodoketones 6, which were not isolated. The suitable β-dicarbonyl compound 2 and α,ω-diamine 3 plus a

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• pyrazolone formation was investigated as the first step of the two step process, we opted to keep the ball size, ball number, jar size and jar and ball material as in our previous studies to reduce the number of variables for this analysis [17]. In the first instance, simply milling the two liquids in the

• absence of an auxiliary material resulted in a poor yield (Table 1, entry 1). Pleasingly, treatment of ethyl benzoylacetate with one equivalent of phenylhydrazine in the presence of sodium chloride afforded the desired pyrazolone product in 66% yield after milling for 10 minutes (Table 1, entry 2). The

• small range of compounds. Conclusion In summary, we have developed a one-pot, two-step mechanochemical synthesis of fluorinated pyrazolones. The experiments provide a logical approach to multistep solventless synthesis under milling conditions and more broadly will assist in the conversion of other

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• milling, sonication, etc. are certainly of interest to the researchers working on the development of green methodologies. In this review, a collection of examples on recent developments in organic bond formation reactions like carbon–carbon (C–C), carbon–nitrogen (C–N), carbon–oxygen (C–O), carbon–halogen

• (C–X), etc. is documented. Mechanochemical syntheses of heterocyclic rings, multicomponent reactions and organometallic molecules including their catalytic applications are also highlighted. Keywords: ball-milling; green chemistry; mechanochemistry; solid-phase synthesis; solvent-free synthesis

• techniques like ball-milling or hand grinding are considered to be promising candidates in solvent-free synthesis [10][11]. Mechanochemical methods deal with chemical transformations induced by mechanical energy, such as compression, shear, or friction [12]. Wilhelm Ostwald, a Russian-German chemist who

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• (CD) derivatives. Activated CDs have been reacted with nitrogen and sulfur nucleophiles using a planetary mill equipped with stainless steel, zirconia and glass milling tools of different sizes. It is shown that the milling frequency and the number as well as the size of the milling balls have an

• effect on the nucleophilic reaction. Keywords: cyclodextrins; milling parameters; nucleophilic substitution; planetary ball mill; Introduction Their hollow structures make cyclodextrins (CDs) a class of carbohydrates that can form inclusion complexes with organic molecules, inorganic salts and complex

• ]. Despite the longer milling times, using less balls allow outcomes to be improved [14]. This work takes the above-mentioned results as a base from which to address the mechanochemical synthesis of 6I-monoazido-6I-monodeoxy-β-CD and 6I-S-monodeoxy-6I-monothiouronium-β-CD tosylate (TU-β-CD), an important CD

Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a liquid medium

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 1850–1856, doi:10.3762/bjoc.13.179

• employed to explain the processes occurring in ball milling [7]. It must also be noted that there is a similar technology available to sonochemistry, that is considered to be less harsh than mechanochemistry, and this is resonant acoustic mixing (RAM). The RAM mixes by controlling the vibration applied to

• that alternative products can be formed using this technique, as with ball milling. The Knoevenagel condensation [18], Michael addition [19] and Biginelli reactions [20] amongst others have been instigated by ultrasonic irradiation in the presence of solvents such as pyridine and methanol, resulting in

• sonochemical reactions being carried out in the absence of solvent, or a liquid reagent [8][9]. Herein, we report two condensation reactions (investigated extensively by ball milling), one to form salen ligand 1 by sonicating o-vanillin and 1,2-phenylenediamine, and the second to form 1,3-indandione 2 from

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• Vjekoslav Strukil Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia 10.3762/bjoc.13.178 Abstract In this review, the recent progress in the synthesis of ureas, thioureas and guanidines by solid-state mechanochemical ball milling is

• highlighted. While the literature is abundant on their preparation in conventional solution environment, it was not until the advent of solvent-free manual grinding using a mortar and pestle and automated ball milling that new synthetic opportunities have opened. The mechanochemical approach not only has

• compromised safety for the researcher. These drawbacks can be eliminated or substantially reduced by the application of automated ball mills. The precise control of parameters such as reaction time, milling frequency, number and size of milling balls, type of milling media (stainless steel, zirconia, teflon

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• biocatalyst for these transformations. Noteworthy, various acyl donors of different chain lengths were tolerated under the mechanochemical conditions. Keywords: ball milling; enzymes; esterification; lignin derivatization; mechanochemistry; Introduction Mechanochemical reactions, particularly those carried

• out by ball milling, have recently attracted attention of a wider scientific community, owing to the many advantages the excellent mixing inside the ball mill can offer [1]. Besides avoiding or minimizing the use of organic solvents as reaction media, chemical transformations by ball milling very

• products or materials [2][3]. In organic chemistry, amino acids and short peptides are not only known for being stable under automated ball milling conditions during their preparation [4], but also when applied as catalysts to perform stereoselective transformations [5][6][7]. Encouraged by these facts, we

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• . Reactions under solvent-free conditions in a ball mill gave good yields and could be put in place of the classical solution conditions. The method is general and can be applied to various imides and alkyl halides. Phthalimides prepared under ball milling conditions were used in a mechanochemical Gabriel

• synthesis of amines by their reaction with 1,2-diaminoethane. Keywords: ball milling; Gabriel reaction; imides; mechanochemistry; N-alkylation; Introduction The development of environmentally friendly organic reactions is a growing area of interest [1]. The reduction of the impact of chemical reactions on

• time, important progress was made in the development of various solvent-free organic reactions [5], especially by the use of the ball milling technique [6][7][8]. In continuation of our interest in eco-friendly organic syntheses [9][10][11][12][13][14], we studied mechanochemical N-alkylation reactions

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• . Several chiral organocatalysts and even enzymes have proved to be resistant to milling conditions, which allows for rather efficient enantioselective transformations under ball-milling conditions. The present article reports the first example of a liquid-assisted grinding (LAG) mechanochemical enzymatic

• resolution of racemic β3-amino esters employing Candida antarctica lipase B (CALB) to afford highly valuable enantioenriched N-benzylated-β3-amino acids in good yields. Furthermore the present protocol is readily scalable. Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic

• ][40][41][42][43][44], so this converts mechanochemistry into a green technique, whose field of application is still very wide. In this context, the use of a minimal amount of solvent (LAG) enable the development of convenient ball-milling protocols. In particular, LAG facilitates mechanochemical

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• milling (HSBM) conditions at room temperature. The effects of milling-ball size, milling-ball filling degree, reaction time, rotation speed and grinding auxiliary category, which would influence the yields of mechanochemical Heck reactions, were investigated in detail. The characterization results of XRD

• easily recovered and reused for at least five times without significant loss of catalytic activity. Keywords: ball milling; Heck reaction; layer double hydroxides; solvent-free; supported Pd catalyst; Introduction High-speed ball milling (HSBM)-assisted transition metal-catalyzed cross-coupling reactions

• of the coupled products with unacceptable Pd species led to a hard separation and recycling of homogeneous catalyst systems. In our previous study [4] we reported a ball-milling Heck reaction catalyzed by Pd(OAc)2. Although the catalyst showed the satisfactory reactivity, it was difficult to recover

Mechanochemical borylation of aryldiazonium salts; merging light and ball milling

• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1463–1469, doi:10.3762/bjoc.13.144

• potential of having both activation modes acting simultaneously. In recent years, mechanochemistry, which encompasses the use of mechanical means by milling, grinding, shearing, cavitation or pulling to induce chemical transformations [3] has become fundamental for discovering new chemical reactivity [4][5

• ] and to develop more sustainable syntheses. Typically, mechanochemical reactions by milling are conducted in non-translucent containers (e.g., agate, ceramics, steels, and tungsten carbide). While this diversity of milling media materials enables controlling, for example, the energy input during the

• translucent milling vessels made of poly(methyl methacrylate) (PMMA) with powder X-ray diffraction (PXRD) [6][7], Raman spectroscopy [8], or a combination of both techniques [9]. On the other hand, attempts to combine photo- and mechanical activation to favor chemical processes have been mainly explored in