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

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• reaction is increased from 68% to 92%. When anthracene was subjected to a milling reaction with succinic anhydride, 9-substituted product 22 was obtained in low yield, and accompanied with a small amount of 2-acylated product 23 (Scheme 4), with same regioselectivity to that reported in the literature [47

• and succinic anhydride. Regioselectivity direction by protection of 9,10-anthracene ring positions. Double FCR of phthaloyl chloride and aromatics. Reaction of pyrene with phthalic anhydridea. Supporting Information Supporting Information File 142: Details of experimental procedures, spectroscopic

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• series of 3-methyleneisoindolin-1-ones 13 were obtained (Scheme 2) [77]. Several aromatic and heteroaromatic substituents can be introduced in the exocyclic methylene position with high regioselectivity. It is noteworthy that arylalkynylcarboxilic acids 11 (R2 = Ar) can be obtained easily by the coupling

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• improve the rate and modulate the regioselectivity and enantioselectivity of reactions [11]. For example, metal-based CD catalytic systems and CD derivatives for organocatalysis have already shown promising results in the studies by Hapiot and Monflier [12], Armspach [13] and others [14][15]. The chemical

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting

• affords 20 in a comparable overall yield of 13%. We conducted a temperature, solvent and base screen to determine what impact these parameters have on the regioselectivity of the alkylation (Table 2). The overall regioselectivity appeared insensitive to the reaction conditions with only a slight decrease

• in selectivity for 6 observed when hydroxylic bases were employed in the reaction (Table 2, entries 1 and 2). Temperature was observed to have no effect on the regioselectivity (Table 2, entries 7, 9 and 10). Similarly, no improvement was observed when other aprotic solvents were used in place of DMF

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• (or amination) sequence on achiral nonfunctionalized cyclopropenes provided the desired cyclopropanol (and cyclopropylamine) derivatives in excellent diastereo- and enantiomeric excesses. Keywords: carbocupration; cyclopropanol; cyclopropene; regioselectivity; stereoselectivity; Introduction The

• facial selection by the catalyst is required: (i) regioselectivity when R1 is different to H and enantioselectivity when R1 is equal to H (left or right) and (ii) diastereotopic face selection (top or bottom) as described in Scheme 2. Since the pioneering addition of a carbon–metal bond (carbometalation

• be addressed carefully as it plays an important role in the control of the regioselectivity of the reaction pathway. An alkyl group on the C1 position of the cyclopropene should control the regioselectivity of the addition of the organometallic species to give the more stable secondary

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• -difunctionalization; regioselectivity; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-D-glucopyranose (Figure 1 illustrates the heptamer, β-CD) that have attracted worldwide interest in various fields of applied supramolecular chemistry due to their ability to form host–guest inclusion complexes [1]. A

• regioselectivity is observed. On the other hand, tosylation under aqueous basic conditions has a different reaction mechanism in which p-TsCl occupies the CD cavity prior to the reaction [23]. This orientation of the first tosyl group has a great impact on the substitution of the second tosyl moiety, which can

• ditosylation reactions and for the observed partial regioselectivity in reaction 2 (Scheme 2). Additionally, a Vilsmeier–Haack/Appel-type iodination reaction was performed with β-CD, using triphenylphosphine (PPh3) and iodine (I2) in DMF (reaction 3, Scheme 2). This reaction is known to be selective for the

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• % yield) and other compounds evidence the participation of radicals [30]. After the efficient conversion of pyrimidine N-oxide PO14 into pyrimidine PM63 no products of this type were isolated. The regioselectivity is another important feature of the Boekelheide rearrangement if alkyl groups are present at

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• , among them the aglycon of scorzodihydrostilbenes B and D. Keywords: C–H activation; hydroarylation; phenols; regioselectivity; ruthenium; Introduction Among phytochemicals with strong allelopathic effects, various natural products are found that feature the structural motif of dihydrostilbene with

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• alkyne terminus. Hydrozirconation/iodination of alkyne 17 required freshly prepared Schwartz reagent (3 equiv) and iodine (3 equiv) to obtain yields of (E)-olefin 18 above 80% with perfect stereo- and regioselectivity. For comparison, as part of a study towards kendomycin, Arimoto and co-workers had