A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• were shown in Scheme 1. Aldehydes 2 with different functional groups on the benzene ring could react smoothly with compounds 1a and 3a, producing the corresponding 3,4-fused tricyclic indoles 4b–d with yields ranging from 46% to 64%. o-Anisaldehyde, with steric-hindrance effect, also reacted

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• binding constants, selectivities or optical responses should have been observed with the variation of the linker length. It may be concluded that the triazole ring, used as a synthetically convenient connection unit, imposes too much steric hindrance and restricted conformational flexibility in the

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• intermediate to undergo subsequent metathesis reactions leading to catalyst deactivation [23]. In both cases, the effect of ethene was especially productive for the Grubbs 1st generation precatalyst and is typically applied for terminal alkynes or alkynes with little steric hindrance of the triple bond. In

• these conditions a full or nearly complete conversion was observed with the exception of the silylated oxaenediyne 2f as was already reported for analogous published substrates [37]. Quite surprisingly, the necessity of a steric hindrance at the propargylic position in the RCEYM forming five-membered

• those using the G-I precatalyst and Mori conditions. The yields gradually improved with increasing steric hindrance of the triple bonds from oxaenediyne 2a (R = H) to 2d (R = Pr) for both precatalysts G-II and HG-II. This observation was in agreement with results reported in reference [23], which proved

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• , the enhanced imbalance in the population of the rotamers of 6a is notable and consistent with the amino moiety imposing a greater steric hindrance. The differences among the other compounds are more modest. The small entropy of activation is consistent with a simple rotation over a steric barrier

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• (Figure 2). The substituents COOH, SH, COO− and O− give rise to almost complete coordination of the cis isomer. In contrast to bimolecular coordination [12] the intramolecular coordination in the substituted cis isomers, obviously, does not follow a clear linear free energy relationship. Steric hindrance

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• iodofluorination at reflux afforded only unreacted starting material. Since iodofluorination is usually more efficient than bromofluorination [19], the decreased yield of (rac)-20b compared to that of (rac)-20a is possibly caused by steric hindrance around the olefin bond, which affects the electrophilic attack of

• compared to bromo- and iodofluorination. However, since Cl+ is smaller and less sensitive to steric hindrance than Br+ or I+, the yield of chloro- and iodofluorination were comparable in this case. The stereochemistry of the above products was determined using NOESY measurements. The formation of two

• steric hindrance – and 33% unreacted starting material was recovered from the iodofluorination reaction mixture. In order to study the synthetic usefulness of the halofluorinated products, E2 hydrogen halide elimination was attempted. Since bromide and iodide are much better leaving groups than fluoride

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• expected, the ortho-substituent on the phenyl ring of the boronic acid impeded N1-arylation by steric hindrance. However, the methoxy and methyl groups at the ortho position did not prevent the formation of the corresponding products 3o and 3p, which were isolated in moderate yields of 52 and 35

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• photodissociable ligands. These ligands coordinate in their trans form and decoordinate in the cis configuration driven by steric hindrance [14][34][35]. Basicity and nucleophilicity switching of the 4-(N,N-dimethylamino)pyridine “record player” molecule 1. Composition of the different states of porphyrin 1 (1 mM

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• the reader. As shown in Tables S1 and S2 in Supporting Information File 1, the equilibrium of the (1-3) arm is not affected by core α(1-3)-Fuc. β(1-2) xylose in plant N-glycans: Because the β(1-2)-Xyl sits in front of the two arms, it greatly affects their dynamics. Because of steric hindrance, the (1

• chitobiose core in a ‘front fold’ either, because of steric hindrance. Also, similarly to the α(1-3) fucosylated glycans, the stability of the open structure is slightly increased when the arm is further functionalized with terminal β(1-3)-Gal, see Table S4 in Supporting Information File 1. As an additional

• completely absent in mammalian N-glycans. Within the context of plant-type N-glycans, which have a terminal β(1-3)-Gal, rather than β(1-4)-Gal, both β(1-2)-Xyl and α(1-3)-Fuc contribute independently in promoting an outstretched (open) conformation of the (1-6) arm because of steric hindrance of the xylose

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• selectivity observed for the reaction did not originate from steric hindrance. Accordingly, the electronic influence of fluorine was explored. Thus, the non-fluorinated analogues bearing a phthalimido group (4) and an alkyl chain (5) were synthesized, and submitted to the ring-opening reaction [27][28

• took place away from the bulky alkyl chain, resulting in the observed E-selectivity. These outcomes were opposite to those obtained with the fluorinated substrate series, consistent with steric hindrance governing the non-fluorine containing oxetane reactions but electronics influencing and reversing

• 95:5 mixture and identified by NMR as the desired bromoalcohols E-9 and Z-9, respectively. The selectivity of the oxetane ring opening (crude E/Z ratio: 89:11) was again governed by the presence of the fluorine atom and not by steric hindrance. In order to limit the competitive formation of the

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• -bromo substituent in the aromatic aldehydes 4b–d and steric hindrance. Both the electron-donating and electron-withdrawing groups in the 2-position were unfavorable for the enantioselectivity (Table 2, entries 2, 9, and 10). The presence of electron-donating groups in the 4-position was more favorable

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• , ethoxy, trifluoromethyl, nitro, and ester underwent efficiently the desired perfluoroalkylation. This coupling was sensitive to steric hindrance as ortho-substituted substrates were less efficiently converted into the desired products. Furthermore, various perfluoroalkyl iodides with different chain

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• repulsions that occur in the equatorial position. Consequently, in the most favorable transition state there is no steric hindrance between the CF3 group and the ethylenic hydrogen, leading to the observed diastereoisomer. On the other hand, the use of 1,9-enyne 18c (n = 3) did not afford the corresponding

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• -disubstituted 1,2,3-triazole derivatives 3g–m in a yield of 72–87%. Alternatively, the ortho- and meta-substituted aryl-MBH adducts were incompatible with the optimized reaction conditions, and this was presumably due to the apparent steric hindrance. Similarly, the MBH adducts derived from aliphatic aldehydes

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• , respectively, were formed as single diastereomers (Scheme 6). The 1-ethyldihydroisoquinoline 20 showed a pronounced lower reactivity to anhydride 8, with a 30% yield of 29 as compared to 28 (71%), probably due to a steric hindrance. The relative configuration of 28 and 29 was established using 2D ROESY NMR

Recent synthesis of thietanes

• Jiaxi Xu

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

• the preparation of 3-monosubstituted and 3,3-disubstituted thietanes but can hardly applied for the preparation of 2,2/2,4-disubstituted, 2,2,4-trisubstituted, and 2,2,4,4-tetrasubstituted thietanes due to steric hindrance in the substitution step. In these cases, the substitution reaction is

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• , partially due to the hyperconjugation of an oxygen lone pair with an antibonding C–F orbital, and partially to the steric hindrance of the -CF3 group [6][7]. These interactions result in a relative conformational flexibility, where the -OCF3 group can rotate between the two sides of the aromatic ring

• most electron-rich site of the arenes, although sensitivity to steric hindrance was observed. The reactions with halogenated aryls occurred smoothly, leading to products 3–11 in good yields. An exception is represented by iodobenzene, which could be methoxylated in only 23% yield (product 6). Similar

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• and intercepted with AN to yield cycloadducts 7 or 11, respectively. However, the formation of cycloadducts is very inefficient, which may be ascribed to a smaller rate constant for the quenching due to steric hindrance imposed by the bulky cyclohexane or adamantine moiety. Thus, irradiation of 2 gave

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• steric hindrance of the bulky ferrocenyl unit could be postulated. Remarkably, ferrocenyl fur-2-yl thioketone (8g) was an exception and delivered a 60:40 mixture of trans- and cis-9m. The mechanistic interpretation of the efficient, formal [3 + 2]-cycloadditions of D–A cyclopropanes 5 with ferrocenyl

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• with a C=C double bond was explained by the steric hindrance of the iminoxyl radical. On the other hand, di-tert-butyliminoxyl radical (8) can react with unsaturated hydrocarbons by abstracting the hydrogen atom from the allyl or benzyl position (Scheme 10) [35][45][60][61]. The C-centered radicals

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• that steric hindrance plays a role during the reaction. Oxazolones 2a–j contain two exocyclic C=C bonds in their skeleton and these can, in principle, have different conformations. The NMR characterization of 2a–j showed that they are obtained as single isomers. The oxazolone exocyclic C=C bond has the

• rings of the cyclobutanes (at C2 and C4) probably resulted in a strong steric hindrance around the already crowded cyclobutane ring, which gave rise to instability and decomposition. However, it is remarkable that all functional groups present in the starting materials 4 (C–F, C–Cl, C–NO2, C–CF3 and –C

• method shows great synthetic potential due to the selective formation of a single isomer, versatility and efficiency (high yields), general applicability and tolerance to the presence of different functional groups, although it is partially limited by steric hindrance in the final step. In addition, this

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• potential of the arylated product and promote oxidative decomposition. Several spirocyclic compounds with larger ring sizes could be coupled to 3-bromopyridine to give products 4c, 4d, 5a and 5b, provided that steric hindrance was not too high (see 5c). Surprisingly, oxetanes appear to be incompatible with

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• enantioselectivities (up to 88% ee) under mild conditions. The chiral-bridged biphenyl monophosphine ligands developed by our group exhibit significant superiority to the naphthyl counterpart MOP in both reactivity and enantioselectivity control. The large steric hindrance from π-conjugated ortho-substituents of the

• (Table 1, entries 2–7). The results show that the higher the steric hindrance of the ligand, the better the yield and enantioselectivity. In order to find out whether the 1’-substituent of the ligand has any influence on the reaction result, we replaced the methoxy group (L3) with an ethoxy group (L8

• ester, the reaction yield rose up from 77% to 90% and the enantioselectivity increased from 35% to 70% (5e, 5f). This indicates that the O···Pd interaction between the carbonyl group and the palladium is not strong enough to determine the enantioselectivity of the reaction solely, the steric hindrance

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• increase of singlet oxygen generation and photocatalytic activity under the sunlight irradiation. Furthermore, the steric hindrance around the porphyrin core, caused by the diacids, enhanced the catalyst photostability, allowing a lowers porphyrin load. The authors evaluated various protonated-TPPs, using

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• Diels–Alder cycloadducts was demonstrated thanks to NOESY correlations observed between protons H-4', H-7'α at 2.30 ppm, H-8' at 3.46 ppm, and H-9' at 3.54 ppm, all on the same cyclohexene α-face. Overall, the facial selectivity of this Diels–Alder reaction seems controlled by the steric hindrance