Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• solvents in the presence of an excess of base [1][2][3]. With the drive for the development of environmentally friendly and low cost protocols, a number of methodologies for the Suzuki–Miyaura reaction under aqueous conditions or in neat water have been reported [4][5][6]. This has been achieved via

• investigation of their catalytic activity in the aqueous Suzuki–Miyaura coupling reaction. Herein, we report the synthesis of the SNS Pd(II) pincer complexes and their interesting catalytic activities in the Suzuki–Miyaura cross coupling reactions in neat water. Results and Discussion Our study commenced with

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• quantitative yields and generally very high enantioselectivities [42][43]. Using the chiral bipyridine ligand 50 and Sc(OSO3C12H25)3 as a catalyst, the asymmetric thiolysis of meso-epoxides 51 in neat water was achieved to provide the corresponding β-hydroxy sulfides in moderate to good yields with high

• reported the use of β-cyclodextrin as a catalyst for the hydroxysulfurization of alkenes with thiophenols in neat water under atmospheric oxygen as shown in Scheme 26 [63]. As opposed to the usual acid-base type of catalysis, β-cyclodextrin having hydrophobic cavities catalyze reactions via formation of

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• reported in literature (3.18 ± 0.01), 2 is still in its anionic dissociated form at pH 4.4. Similarly, a neat increase of the sequestration percentage occurs, on increasing the pH from 6.7 to 10.7, for the basic diamine derivative 5 (pKBH+ = 10.19 ± 0.01), which passes from its cationic to its neutral form

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• the neat crude product at rt, along with 52% of 4-iodoanisol (see Supporting Information File 1). This observation is in line with a ligand-coupling (LC) mechanism [30][35][36] where the observed byproduct could be the T-shaped intermediate 9 or the corresponding 4-coordinated species with two

• room temperature and could be converted to the arylated products upon heating. The reactivity of 9 is unusual, as it proved stable to neutral work-up with brine, formed product 3 upon longer reaction time or rt storage in CDCl3 or neat, but decomposed to starting materials upon work-up with sat

Recent advances in phosphorescent platinum complexes for organic light-emitting diodes

• Cristina Cebrián and
• Matteo Mauro

Beilstein J. Org. Chem. 2018, 14, 1459–1481, doi:10.3762/bjoc.14.124

• fabricated OLEDs using phosphor 13 as emitting layer was ITO (100 nm)/TAPC (80 nm)/4,4’,4’’-tri(9-carbazoyl)triphenylamine (TCTA) (10 nm)/Pt(fppz)2 neat (30 nm)/1,3-bis(3,5-di(pyridin-3-yl)phenyl)benzene (BMPYPB) (15 nm)/BMPYPB:1 wt % Rb2CO3 (40 nm)/Al (100 nm). These devices exhibited an outstanding EQE

• phenyl ring. As the parent complex 23a, excimer formation via metal–metal interactions was observed for both derivatives at high concentrations or in neat films. Nevertheless, the increased conjugation within the chromophoric ligand led to a lower emission energy, which fell into the NIR region. The

• and high thermal stability. Unfortunately, going from dilute solution to neat solid-state samples, PLQY values dramatically dropped to values as low as 0.10–0.02 that might point to strong intermolecular interaction and TTA phenomena. The tendency toward aggregation for complex 44 and 46 in condensed

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• derivatives, Sikchi and Hultin contrived an attritor-type mill (Figure 1c) to facilitate the use of neat reagents and vent CO2 (closed vessels were reported to break) [19]. Efficient gram-scale Boc protection of amine and carboxylic acid functions was thereby effected (Scheme 3). This chemistry was further

Bromide-assisted chemoselective Heck reaction of 3-bromoindazoles under high-speed ball-milling conditions: synthesis of axitinib

• Jingbo Yu,
• Zikun Hong,
• Xinjie Yang,
• Yu Jiang,
• Zhijiang Jiang and
• Weike Su

Beilstein J. Org. Chem. 2018, 14, 786–795, doi:10.3762/bjoc.14.66

• energy and reactant [53][54][55]. Thus, the effect of the grinding auxiliaries was also investigated. The results were shown in Table 2. Compared to using silica gel as grinding auxiliary, the reaction under neat conditions gave only 10% yield of 3aa, but the dehalogenation was depressed (Table 2, entry

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• ; nanoreactors; micelles; polymersomes; Introduction It is widely acknowledged that “the best solvent is no solvent”; however, running a reaction under neat conditions is very challenging from the points of view of mass transfer and temperature gradients [1][2]. Therefore, sustainable chemical technologies are

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• + Na]+ calcd for C18H18B2N2, 307.1548; found, 307.1561; IR (neat): 3124, 3041, 2965, 2918, 2829, 1581, 1468, 1425, 1310, 1286, 1276, 1153, 1113, 997, 950, 889, 754, 713, 610, 575. IEDDA reactions catalyzed by the air-stable bidentate Lewis acid catalyst B General procedure A for IEDDA reactions of

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• in a continuous stirred tank reactor (CSTR). The last step requires the reaction of 12 with 4,7-dichloroquinoline (13) which when used neat takes 24–48 hours at 120–140 °C to give 75–80% yield of HCQ (1) [37]. We have found that this step can be accelerated by employing K2CO3/triethylamine, to

• Information File 1) 10 reacts rapidly and cleanly with 7 under flow conditions to give 6 in high yield (>80%). Furthermore, we have developed and optimized a continuous synthesis of 10 (Table 1), wherein hydroiodic acid is reacted with neat 3-acetyldihydrofuran-2(3H)-one (8) to provide a rapid route to 10

• of 68% for compound 12. With an optimized continuous process for producing the key intermediate 12 in-hand the reaction conditions for the conversion of 12 to HCQ (1) were examined. In the commercial process this step is carried out in batch under neat reactant conditions and requires a relatively

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• (t, 3H, J = 7.0 Hz); 13C NMR (75 MHz, CDCl3) δ 164.3, 162.3, 151.1, 134.0, 131.2, 123.7, 122.7 (q, J C-F = 282.9 Hz), 80.7 (q, J C-F = 30.4 Hz), 63.2, 16.6, 13.8; 19F NMR (282 MHz, CDCl3) δ −78.4 (s, 3F); HRMS (APCI-TOF): [M]−· calcd for C13H12F3NO6, 335.0617; found, 335.0623; FTIR (neat, cm−1) 784

• = 289.90 Hz, JF-H = 56.4 Hz, 1F); HRMS (APCI-TOF): [M + Na]+ calcd for C13H14F2NaO4, 295.0758; found, 295.0761; FTIR (neat, cm−1) 1026, 1093, 1114, 1216, 1279, 1388, 1452, 1602, 1730, 1747, 2938, 2985, 3021; [α]D25 −7.47 (c 1.01, CHCl3); HPLC (column, CHIRALCEL OJ-3, hexane/2-propanol 99:1, flow rate 0.6

• = 288.2 Hz, 1F), −123.882 (s, 2F); HRMS (APCI-TOF): [M]−· calcd for C15H12F7NO6, 435.0553; found, 435.0547; FTIR (neat, cm−1) 1090, 1140, 1200, 1233, 1349, 1387, 1534, 1609, 1744, 1761, 2942, 2988, 3059; [α]D25 −22.60 (c 0.94, CHCl3); HPLC (column, CHIRALCEL OJ-3, hexane/2-propanol 99:1, flow rate 0.6 mL

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• acid nanoparticles (ASA NPs) proved to be efficient under neat conditions for the synthesis of 1-amidoalkyl-2-naphthols [19]. Zali et al. carried out this synthesis applying nano-sulfated zirconia [20], Borhade et al. used PbS nanoparticles [21], while Safari et al. applied magnetic-nanoparticle

• naphthoxazino-isoquinoline derivatives 43 under neat conditions staring from 1-aminoalkyl-2-naphthols and 6,7-dimethoxy-3,4-dihydroisoquinoline was observed [79]. At the same time, Osyanin et al. reported the same reaction extended by various substituted aminonaphthols [80]. Achieving the syntheses in ethanol

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• . This transformation is perhaps similar to acetal hydrolysis in neat water under microwave irradiation [41]. Because of this efficient process, compound 11 was isolated in one synthetic operation in 80% yield from amine 9. In the last step, precursor 11 reacted with either amine (R,R)-12 or (S,S)-12, to

Continuous-flow retro-Diels–Alder reaction: an efficient method for the preparation of pyrimidinone derivatives

• Imane Nekkaa,
• Márta Palkó,
• István M. Mándity and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2018, 14, 318–324, doi:10.3762/bjoc.14.20

• selected to comprise molecules where good (>80%), medium (70–80%) and no conversion was observed under batch rDA conditions. Batch reactions were carried out by the following ways: heating under neat conditions, refluxing in solvents having a high boiling point [chlorobenzene (CB) or 1,2-dichlorobenzene

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• groups on the 9,9-dimethyl-9,10-dihydroacridine units, this molecule proved to be also nearly insensitive to the concentration, showing an emission maximum for the neat film at 470 nm which is almost similar to that obtained for a 10 wt %-doped mCP film (462 nm where mCP stands for m-bis(N-carbazolyl

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• purification was required, which was convenient on scale. The reaction of (±)-trans-2 with neat Et3N·3HF at 120 °C for 16 h led, after aqueous work-up, to (±)-anti-3 in high diastereomeric purity (see Supporting Information File 1). The 19F shift of −195.3 ppm is different compared to that of (±)-syn-3 (−204.4

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• , 134.6, 136.8; 19F NMR (470 MHz, CDCl3) δ 124.7 (br s); IR (neat): 3068, 1489, 1454, 1126, 1147, 1097, 964, 850, 742, 696, 592 cm−1; HRMS–EI (m/z): [M]+ calcd for C21H15F2I, 432.0186; found: 432.0166. Typical procedure for the iodoarylation of 2-(3,3-difluoroallyl)biaryls 5: To a HFIP (2.5 mL) and

• ), 134.6, 138.6 (dd, JCF = 5 Hz), 140.3; 19F NMR (470 MHz, DMSO-d6, 120 °C) δ 72.3 (d, JFF = 236 Hz, 1F), 86.5 (d, JFF = 236 Hz, 1F); IR (neat): 3068, 3030, 1450, 1149, 1055, 989, 752, 598 cm–1; HRMS–EI (m/z): [M]+ calcd for C15H11F2I, 355.9873; found: 355.9866. ORTEP diagram of 2a with 50% ellipsoid

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• . For all compounds DEPT-135, COSY, HSQC, and HMBC were run and used in the structural assignment. IR spectra were recorded neat (ATR sampling) with the intensities of the characteristic signals being reported as weak (w, <20% of tallest signal), medium (m, 20–70% of tallest signal) or strong (s, >70

• 162.8 (C), 147.6 (C), 133.3 (q, J = 35 Hz, C), 132.4 (CH), 131.0 (q, J = 4 Hz, CH), 128.9 (C), 123.7 (q, J = 4 Hz, CH), 122.2 (q, J = 273 Hz, C), 113.8 (C), 64.4 (CH2), 41.2 (CH), 13.9 (CH3); 19F NMR (376 MHz, CDCl3) δ −63.2; IR (neat) ν/cm−1: 3092 (w), 2925 (w), 1732 (m), 1537 (m), 1502 (m), 1357 (m

• 164.4 (C), 135.8 (d, J = 3 Hz, CH), 128.7 (C), 125.4 (q, J = 273 Hz, C), 123.3 (q, J = 34 Hz, C), 121.75 (CH), 118.0 (q, J = 4 Hz, CH), 117.6 (C), 110.3 (q, J = 4 Hz, CH), 107.5 (C), 59.8 (CH2), 14.9 (CH3); 19F NMR (376 MHz, DMSO-d6) δ −59.3; IR (neat) ν/cm−1: 3196 (m), 1667 (s), 1514 (m), 1440 (m

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• compounds to promote a reaction, by inducing the breaking/forming of covalent or supramolecular bonds [1][2]. There are different approaches towards mechanochemistry. The most direct is neat grinding (NG), in which the reagents are ground together without the addition of any solvent or other additive [3

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• until 2011. Trifluoromethylations with [(PPh3)3CuCF3] are only efficient when the reactions are performed in neat aryl iodode [14]. Less side-products and higher yields are observed for trifluoromethylations with [(PPh3)3CuCF3] when dtbpy (dtbpy = 4,4′-di-tert-butylbipyridine) is added to reaction

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

• from a set of triplicate measurements. Variation close to the onset of milling may be due to poor initial homogeneity of the sample. The reproducibility of varying milling frequency on the neat mechanochemical condensation of benzil and o-phenylenediamine, as measured by triplicate experiments. The

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• ethyl acetate in hexane to provide the coupled product as colorless viscous liquid. (S,E)-1-tert-Butyl 8-methyl 7-(tert-butoxycarbonylamino)oct-2-enedioate (14a) Colourless liquid. Yield: 148 mg, 83%; [α]D25 +12.60 (c 1.00, CHCl3); IR (neat): 3363, 2978, 2933, 1715, 1652, 1505, 1367, 1164 cm−1; 1H NMR

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

• coupling products in satisfying purity and in isolated yields ranging from 78 to 89%. Of note, it was observed previously under similar reaction conditions that the absence of EtOAc as liquid grinding assistant (neat grinding) could lead to inhomogeneity of the reagents distribution inside the ball-mill

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

• ; mechanochemistry; multistep; solid-state synthesis; Introduction Mechanochemical methods are emerging as an alternative approach to traditional solvent-based reactions for chemical synthesis. Under mechanochemical conditions reactions are performed between neat reagents and do not require a solvent. Processing

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

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

• were screened with electron-donating and electron-withdrawing groups attached to aromatic rings. The reactions were performed in a 1:1 stoichiometry by manual grinding in a mortar and by automated ball milling in a laboratory mixer mill. Also, the performance of solvent-free or neat grinding was

• )-(+)-1,1′-binaphthyl-2,2′-diamine in a stoichiometric ratio. The corresponding chiral bis-thiourea organocatalysts were isolated in ≥99% yields after only 20 minutes (60 min in the case of binaphthylthiourea) of neat grinding or LAG. Interestingly, while the solution synthesis of (1R,2R)-8 in THF followed

• dithiocarbamate salt 23 (Scheme 8a). In comparison with 24 h reactions carried out in solvents (CH2Cl2, THF, acetone, methanol, DMF, DMSO or neat CS2), the mechanochemical synthesis was rapid and furnished electron-rich isothiocyanates in high yields in 40–45 minutes (e.g., 24a–c). On the other hand, anilines