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

• enantioselectivity was reported by Hartwig et al. in 2016 [99]. The newly formed C–B bond reacted with a range of electrophiles to deliver products containing C–C, C–N, and C–X (X = Br, Cl) bonds (e.g., 349, 350). Efforts to explore the mechanism revealed a decrease in regioselectivity when the C=C bond is further

• (307) was established using CuBr/JohnPhos/LiO-t-Bu and CuCl/IMes/NaO-t-Bu, respectively, in the presence of I-CH2F (361) as the methylfluorinating agent, affording products reflecting excellent control of regioselectivity. This transformation is useful for the synthesis, e.g., of monofluorinated

Direct borylation of terrylene and quaterrylene

• Haruka Kano,
• Keiji Uehara,
• Kyohei Matsuo,
• Hironobu Hayashi,
• Hiroko Yamada and
• Naoki Aratani

Beilstein J. Org. Chem. 2020, 16, 621–627, doi:10.3762/bjoc.16.58

• quite limited because they must suffer the harsh conditions of the rylene skeleton preparation. Basic reactivity of rylenes with electrophiles is predicted from perylene in which the most reactive sites are the 3,4,9,10-positions [21]. On the other hand, the regioselectivity of the iridium (Ir

• )-catalyzed direct C–H borylation [22][23][24][25] gives 2,5,8,11-tetraborylated perylene [26]. The regioselectivity of the perylene borylation is determined by the steric factors rather than by the electron distribution in the arene and this regioselectivity complements that of electrophilic substitutions

• [26]. In light of the above, we plan to perform the Ir-catalyzed direct borylation of C–H bonds in terrylene because 1) the regioselectivity of the reaction is unique and should be remarkably high, thus terrylene will be borylated at the 2, 5, 10, and 13 positions, which don’t deform the rylene cores

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• arylation; nonprecious metal catalyst; copper catalysis; polycyclic aromatic hydrocarbons (PAHs); regioselectivity; Introduction Polycyclic aromatic hydrocarbons (PAHs) with rigid planar structure, such as naphthalene, phenanthrene, pyrene and their derivatives, can usually emit relatively strong

Synthesis of triphenylene-fused phosphole oxides via C–H functionalizations

• Md. Shafiqur Rahman and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2020, 16, 524–529, doi:10.3762/bjoc.16.48

• catalyst (Scheme 2). This one-pot construction of the benzo[b]phosphole core ensured the preferential phosphole ring closure in proximity of the alkoxy group of the arylzinc reagent 1 (regioselectivity of ≈3:1), presumably due to a secondary interaction between the MOM group and the cobalt catalyst during

• ]phospholes [36][37][38][39][40], this three-component method guarantees a good regioselectivity for the formation of the desired 7-hydroxybenzo[b]phosphole derivatives. The triphenylene moiety was completed in the last step through a Scholl reaction. The synthesized triphenylene-fused phosphole oxides showed

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• /iodoarene direct arylation method reported by Larrosa is notable: proceeding in high yields, at room temperature, and with no reported regioselectivity issues (Scheme 1) [12]. This system is hypothesized to proceed under mild conditions due to a highly electrophilic Pd catalyst generated in situ. In this

• ring. Finally, branching is evidenced by the discrepancy in molecular weight as calculated for a linear polymer by 1H NMR compared with that indicated by MALDI–TOF MS (Figure 2). Due to the high regioselectivity in small molecule couplings, defects to this extent were unexpected. MALDI–TOF MS was

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

• yields starting from the corresponding N-vinylpyrroles 103 and 104 (Scheme 19). The N-isopropenylpyrrole precursor 104 gave the adducts with 100% regioselectivity. More recently a solvent and catalyst-free method has been reported for vinylpyridines [97]. Preparation of N-heterocyclic phosphines via P–N

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• metal catalysis, which include: (i) excellent regioselectivity of the targeted C–H bond formations thanks to favorable dissociation enthalpies and electronic properties as compared to other concurrent C–H bonds; (ii) avoidance of an extra oxidant because the reaction proceeds with overall redox

• bonds. C–H olefination Weinreb amide C–H olefination: Photoredox catalysts carry the reactions forward with high regioselectivity, good functional group tolerance, and with or without an external oxidant at low temperatures. However, without photoredox catalysts, the earlier syntheses suffered from the

• the aid of photoredox catalyst 12a, the reaction took place under mild conditions with high regioselectivity and excellent functional group tolerance, as shown in Scheme 11 [127]. On the other hand, Xu and co-workers reported the preparation of arylated products via dual photoredox catalysis using the

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• and 89% ee with EtMgBr (Scheme 2b). To overcome the low regioselectivity, the authors took into account previous works showing that the 1,4-regioselectivity in the addition of cuprates to enals could be improved in the presence of a slight excess of TMSCl [15][16][17][18][19]. Indeed, using TMSCl in

• combination with (R)-TolBINAP (L3), a promising 85% regioselectivity was observed, without altering the enantioselectivity (90% ee), whereas only 32% of the desired 1,4- product was obtained without TMSCl [20]. With those optimized conditions, various enals and Grignard reagents were screened. Nevertheless

• methodology was also tested on linear polyenic thioesters [9]. The challenging 1,8- and 1,10-products 21a/b were obtained, but the stereoselectivity dropped when the distance between the reacting olefin and the ester function was increased (1,8-ECA 72% ee; 1,10-ECA 45% ee). However, the regioselectivity (59

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• ) afforded the linear allylation product 3aa with complete regioselectivity. The symmetric secondary allylic carbonate was converted to the corresponding homoallylic alcohol derivative in 50% yield (3af). To gain understanding into the mechanism of this synergistic palladium/copper-catalyzed allylic cross

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• were obtained in short reaction time, high yield and purity without the need of any solvent when allenylboronic acid pinacol ester was used, or using a minimal amount of acetone when potassium allenyltrifluoroborate was used. Keywords: boron compounds; microwave; propargylation; regioselectivity

• there are several stereoselective methods described for the reaction of propargyl or allenyl organometallics with carbonyl compounds [8][9][10][11][12][13][14], the control of the regioselectivity is still a major concern. This is mainly due to the metallotropic rearrangement of propargyl and allenyl

• organometallics in solution resulting in mixtures of the two reagents [15]. Thus, upon reaction with an aldehyde, mixtures of propargylic and allenic alcohols can be obtained through a chelate transition state (SE2'). Attempts to improve the regioselectivity of the propargylation reaction by using allenic

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• -containing oligosaccharides with the desired regioselectivity is to regioselectively protect the Neu5Ac acceptor. Although Neu5Ac with a free primary OH-9 function is easy to obtain, there are only limited ways to distinguish the secondary OH-4 and OH-7 group (Figure 1). In our previous report, we easily

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• Universitaria, 1428 Buenos Aires, Argentina 10.3762/bjoc.15.294 Abstract Regioselective glycosylations allow planning simpler strategies for the synthesis of oligosaccharides, and thus reducing the need of using protecting groups. With the idea of gaining further understanding of such regioselectivity, we

• regioselectivities were achieved in favor of the 1→3 products due to the equatorial orientation of the OH-3 group. A molecular modeling approach endorsed this general trend of favoring O-3 substitution, although it showed some failures to explain subtler factors governing the difference in regioselectivity between

• some of the acceptors. However, the Galp-(β1→3)-Galp linkage could be regioselectively installed by using some of the acceptors assayed herein. Keywords: Fukui indexes; galactopyranosyl acceptors; galactose donors; molecular modeling; regioselectivity; Introduction Given the importance of

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• literature procedure, 2,3-dibromobenzofuran (1) was synthesized by bromination of benzofuran [33]. The Suzuki–Miyaura reaction of 1 with 2-bromophenylboronic acid (2), carried out under standard conditions using Pd(PPh3)4, afforded the desired product 3 in 84% yield and with very good regioselectivity. The

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• intermediate 9, we turned our attention to investigating the reaction of internal alkynes 11 to examine the regioselectivity of the hydration process. Ester, sulfone, and phosphonate substrates were employed and, in all cases, the internal alkyne unit was capped by an ethyl group (Scheme 2). In general

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• borylated, the choice of a suitable pyridine-hydrazone ligand [42] allowed to perform the borylation reactions at 55 °C, showing complete regioselectivity in the C–H borylation. This procedure afforded the dyes 16–19 in good to very good yields of 51–83% (Scheme 3). The introduction of the Bpin moiety

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• regioselectivity, can be overcome when a suitable directing group assists the reaction [46][47]. Traditional directing groups for C–H activation include amide, hydroxamide, carboxylate, pyridyl, quinolyl, carbonyl, ether, hydroxy, oxazolinyl and cyano [47]. For example, Ackermann et al. reported a Ru(II)-catalyzed

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• period. In recovered starting material 9d-D deuterium incorporation (about 60% calculated from the NMR resonance of 5-H) was detected exclusively at C-5, clearly indicating the regioselectivity of this metalation (Scheme 2). Probably, the metalation rate is even higher than 60% (compare the 71% yield for

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

• stoichiometric amounts and/or toxic reagents [14]. Also, low functional group tolerance, being limited to activated arenes, the production of metal salts as stoichiometric byproducts, and poor levels of regioselectivity would always be observed, limiting the progress of fluorine chemistry to some extent. In this

• nucleophilic fluoride source was reported by Doyle and co-worker (Scheme 5) [39]. Herein, the authors utilized a Pd/Cr cocatalytic system to generate the allylic fluorides with high regioselectivity (branched > linear). Alkyl fluorination of acidic carbonyl compounds and other compounds: In 2012, the group of

• achieved using Et3N·3HF as the fluorine source with a high catalyst loading (20–30 mol %) affording the products in 45–92% yield [70]. The heteroatom-containing functional group (R1) is necessary for good reactivity and regioselectivity. α-Fluorination of acidic carbonyl compounds: In 2011, Shibatomi and

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• functionalization [3][4][5][6]. The metal carbene reactions with indoles have been studied for the three types of carbenoids: acceptor–acceptor [7][8][9], mono-acceptor [10] and donor–acceptor carbenoids [11][12][13][14]. Depending on the metal and the diazo compound, the chemo- and regioselectivity in the metal

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• obtained in a 64:36 ratio. Then, the influence of some bases on the regioselectivity with Pd(OAc)2 catalyst was examined. With CsOAc a similar regioselectivity than with KOAc was obtained, whereas the use of NaOAc afforded the products 1a and 1b in an 85:15 ratio, but with a moderate conversion of 3

• (C3H5)(dppb) catalyst [39] was employed. With K2CO3 and Na2CO3, the conversion of 3-bromobenzonitrile was not improved, whereas using NaOAc, a complete conversion of the aryl bromide was observed (Table 1, entries 8–10). Moreover, the regioselectivity in favor of α-arylated lilolidine was improved to 93

• % affording 1a in 83% yield. The use of KOAc associated to PdCl(C3H5)(dppb) catalyst also afforded the regioisomer 1a in a quite good regioselectivity and yield (Table 1, entry 11). The higher conversions observed in the presence of acetate bases compared to carbonate bases (Table 1, entries 4–6 and 8–11

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• 5/6/8/5 tetracyclic intermediate. This, in turn, is transformed to a 4/6-membered ring in quiannulatene biosynthesis, whereas 5/5 ring formation proceeds in sesterfisherol biosynthesis (Scheme 1, Scheme 2, and Scheme 3). Based on our DFT calculations, this regioselectivity is determined by the

• conformational changes take place in quiannulatene biosynthesis, in which C24 and C25 are highly mobile. On the other hand, C8, C9 and C21 are quite mobile in sesterfisherol biosynthesis. These different mobility trends result from the different types of conformational change required to achieve regioselectivity

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

• opening with nucleophiles, e.g., oxygen, can relatively easily be achieved [12], and for the structural framework of 5–8 occurs with high regioselectivity at the less substituted carbon atom, aldehydes (2R,1'R)- or (2R,1'S)-6 are considered as synthetic equivalents of (R)- or ᴅ-serinal while (2S,1'R)- or

• aziridine moiety into the 2-cyano-1-(methylamino)ethyl group was carried out after N-Boc protection and involved methylation of (2R,3'R,1''S)-73 with simultaneous opening of the aziridinium ion with cyanide to form (3S,3'R,1''S)-74 with high (97:3) regioselectivity. The removal of the chiral auxiliary

• stereospecific crotylation with a homochiral boronate to give the aziridine alcohol (2R,1'R,2'R,1''R)-140 (Scheme 36) [90]. After O-benzylation and N-methylation the ring opening in the intermediate aziridinium ion was tried. It appeared that the best regioselectivity (87:13) was achieved with cesium acetate and

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

Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• regioselectivity and reaction trajectory of the 1,3-dipolar cycloaddition reaction by steric hindrance. The obtained novel isoxazoline-substituted porphyrin derivatives 3a,b have been characterized by absorption, emission, NMR and mass spectrometry. In addition, the crystal structure of 3a is discussed. Results