Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• diradicals as intermediates. To explain the regioselectivity, theoretical calculations were performed with thiochalcone and acrylonitrile as model substrates. For the frontier molecular orbital treatment, the largest coefficients in both HOMO and LUMO of thiochalcone existed on the sulfur atom, while the

• largest coefficients in both HOMO and LUMO of acrylonitrile were located at the β-carbon atom. These favored the overlapping between the sulfur atom and the β-carbon atom, deciding the regioselectivity [76][77] (Scheme 51). Interestingly, the photochemical behavior of thioenones was obviously different

• thiiranes 419 from the least substituted ring carbon atom generated the zwitterionic intermediates 427, with a good regioselectivity following the general regioselectivity rule in nucleophilic ring opening reactions of aliphatic three-membered heterocycles [124][125][126][127][128][129][130][131][132]. The

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• hydroborations proceeded with the exclusive formation of isoxazolidines with a hydroxy group in the C-4 position. We assume that the excellent regioselectivity is unambiguously caused by electronic effects since the endocyclic oxygen atom donates electrons to the C=C double bond, developing a negative partial

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• ) afforded the three isomeric o, m, and p-fluoro-ʟ-phenylalanines 46, 67, and 68, in ratio 72.5:13.9:13.6, respectively. In this reaction, [18F]AcOF showed a higher regioselectivity and less side product formation compared with [18F]F2 [52] (Scheme 15). The radiolabeled compound, 4-borono-2-[18F]fluoro-ʟ

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

• an N-acyl-4-methoxypyridinium salt using a copper/phosphoramidite catalytic system (Scheme 3) [20][21]. The authors highlighted that the N-acylpyridinium salts were unstable species and that their instability affected the regioselectivity of the dearomatisation process upon the nucleophilic addition

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• could be circumvented through ligand modification. Phenol oxidation is ubiquitous in biological systems as demonstrated by the involvement of the copper enzymes tyrosinases (type III) in the melanogenesis process. The regioselectivity and reactivity of the oxidation of phenols are strongly dependent on

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• good yields of 145h–l (Scheme 32). Additionally, products derived from ureas (i.e., 146), N,N-dimethylaniline (i.e., 147), amides (i.e., 148), and lactams (i.e., 149a) were obtained. Moreover, for N-methylpyrrolidinone, α-arylation was achieved in a good yield and regioselectivity for the substitution

One-pot synthesis of dicyclopenta-fused peropyrene via a fourfold alkyne annulation

• Ji Ma,
• Yubin Fu,
• Junzhi Liu and
• Xinliang Feng

Beilstein J. Org. Chem. 2020, 16, 791–797, doi:10.3762/bjoc.16.72

• an efficient method to develop π-extended aromatic hydrocarbons with cyclopenta moieties. Keywords: alkyne annulation; cyclopenta-fused polycyclic aromatic hydrocarbons; nonplanarity; peropyrene; regioselectivity; Introduction Significant efforts have been recently devoted to the synthesis of

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• synthetic protocol for the preparation of trifluoromethyl(indolyl)phenylmethanols is operationally simple and provided products in high yields without requiring silica gel column chromatography. The reaction has a broad substrate scope and proceeds with high regioselectivity. The recovery and reusability of

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• shown that the regioselectivity of the nucleophilic fluorination of amino alcohols can be controlled depending on the fluorinating reagent used [30][31]. This work presents the optimization of nucleophilic fluorination conditions. What is more, we discuss the effect of the base used on the

• regioselectivity of the fluorination reaction. The absolute configuration of the obtained compounds was determined and confirmed by X-ray analysis. Furthermore, we present the use of α-fluorinated β-aminophosphonates as building blocks in the synthesis of their dipeptide analogues. In addition, we show the results

• not observe a complete regioselectivity of the fluorination reaction. Nevertheless, in each case, the use of PyFluor as a nucleophilic fluorinating reagent and MTBD as an activator improved the regioselectivity of this reaction, as well as, the yield of the α-isomer 11 (best results are shown in Table

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