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

• , pyrimidines, and oximes (Figure 20). The mild arylation proceeded in good to excellent yields over 20 examples and worked with electron-deficient, electron-rich as well as relatively sterically hindered arylating reagents. The mechanism proposed by the authors is presented in Figure 21. First, the DG-assisted

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

• aromatic heterocycles have a low tendency to undergo reactions with cyclic anhydrides, resulting in low to moderate overall yields of the target products [12][27]. Further research by Krasavin et al. on the reactivity of sterically hindered indolenines in reactions with anhydrides 6–9, did not give the

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• nucleophilicity of pyridine compared with the tertiary alkylamine present in compound 12 [45][46] may be responsible for the lower vulnerability of 9 towards alkylation. Another approach to circumvent the formation of N-alkylation products was based on the use of the more sterically hindered diisopropyl

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• ″) for the tert-amyl alcohol addition (Figure S4, Supporting Information File 1). Finally, we explored the formation of sterically hindered oxygen bases by a direct alcohol deprotonation. Knochel-type tert-amyl magnesium alkoxide (t-AmylOMgCl⋅LiCl) 1.0 M (95%) was obtained (≈15 mL) by the reaction of 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

• isomer), the use of bulky, sterically hindered ʟ-selectride in anhydrous THF at 0 °C led to the formation of the cis product exclusively (Scheme 4) [35][36], and the C-3/4-cis 4-hydroxyisoxazolidine 10a was isolated in 76% yield. Its relative configuration was confirmed by means of NOESY 1D experiments

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

• , and its dipole moment in the benzene solution was measured (2.90 D). Besides the mentioned sterically hindered iminoxyl radicals 8 and 16, iminoxyl radicals with electron-withdrawing substituents at the C=NO• fragment also demonstrate increased stability compared to ordinary alkyl and aryl iminoxyl

• established that the studied iminoxyl radicals reversibly dimerized in the solution. For sterically unhindered dialkyliminoxyl radicals, the radical–dimer equilibrium was quickly reached, shifted toward the dimer, while a first-order decay kinetics of was observed for the iminoxyl radical. For sterically

• hindered tert-butylmethyliminoxyl and diisopropyliminoxyl radicals, as well as for diaryl and alkylaryliminoxyl radicals, the radical–dimer equilibrium was reached slowly, it was shifted toward the free radical, and a second-order decay kinetics was observed. The first synthesized long-lived iminoxyl

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

•  14, a). One year later, they demonstrated that these copper-based reagents ((Phen)CuCF2RF, RF = F, CF3 and CF2CF3) were efficient in a two-step sequence reaction (borylation/perfluoroalkylation) allowing the functionalization of either sterically hindered arenes or aryl bromides with the CF2CF3 and

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

• heterocyclic group, an electron-rich aromatic or an electron-deficient aromatic group, the reaction always performed well with high yield and good enantioselectivity. We guess that the large sterically hindered π-plane formed between a carbonyl group and a benzene ring is the guarantee of high ee values of the

Preparation and in situ use of unstable N-alkyl α-diazo-γ-butyrolactams in Rh^II-catalyzed X–H insertion reactions

• Maria Eremeyeva,
• Daniil Zhukovsky,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2020, 16, 607–610, doi:10.3762/bjoc.16.55

• found to be unstable and to undergo unproductive dimerization to bishydrazones, were successfully converted immediately to various X–H insertion products with alcohols, aromatic amines and thiols via an in situ RhII-catalyzed reaction. With aliphatic amines or unreactive, sterically hindered anilines

• , that we observed with 2,6-dimethylaniline. With this unreactive, sterically hindered aromatic amine, 6c is likely to undergo either the unwanted N2→O oxidation or dimerize to bishydrazone 5, whereupon the resulting intermediate would be eventually trapped by the aniline to give 8b (Scheme 2). The

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• BODIPY plane for both derivatives, indicating the rigid interlocked structures of 3a and 6b by the bulky o-methyl groups. In particular, the β-methyl substituents of 6b are sterically hindered by the neighbouring meso-aryl ring. The regioselective 2,6-diethynylation of 6a through the above alkynylation

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• chlorosulfonylation of terminal alkenes and alkynes using the previously developed copper-based photocatalyst (Scheme 19) [35]. The reaction was tolerant to a broad range of arylchlorosulfonyl derivatives when the reaction was carried out with styrene, including sterically hindered and heteroaromatic substrates

Six-fold C–H borylation of hexa-peri-hexabenzocoronene

• Mai Nagase,
• Kenta Kato,
• Akiko Yagi,
• Yasutomo Segawa and
• Kenichiro Itami

Beilstein J. Org. Chem. 2020, 16, 391–397, doi:10.3762/bjoc.16.37

• present method. The analyzed structure from X-ray crystallography confirmed the regioselective C–H borylations at the least sterically hindered C–H bonds of HBC. Optoelectronic measurements of 1 revealed bathochromic shifts of the absorption bands compared with unsubstituted HBC. DFT calculations also

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

• CuBr∙SMe2/(R,S)-Josiphos (L9). However, the catalytic system was poorly selective toward sterically hindered organomagnesium nucleophiles (15–25% ee). The synthetic versatility of the thioester function was illustrated in the synthesis of (−)-lardolure (26% overall yield over 12 steps) via a relevant

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• . Using the optimized protocol, compounds 1a–k were synthesized in high to excellent yields (Table 1). The more sterically hindered derivatives 1l,m required significantly longer reaction times. Thionation of the resulting amidoester 1a with Lawesson's reagent (LR) was then examined. Using the reagent in

• /water (30 min, 70 °C) afforded thioamido alcohol 3a (95%). Thioaroyl derivatives 3b–k were prepared in high to quantitative yields under these experimental conditions, except for the more sterically hindered 2-methylphenyl derivative 2h, which required a longer reaction time (1 h) to achieve complete

• products (Table 2). Ring closure of the more sterically hindered isobutyryl and pivaloyl thioamidoalcohols 3l,m was also successful, requiring slightly higher temperatures. Mechanistic considerations The cyclization of 4-amidobutanols promoted by PPA esters leads exclusively to N-acylpyrrolidines instead

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

• in the synthesis of inhibitors for N-acetylneuraminidases from different sources [42]. The ring opening of 5 was not trivial since the substrate had a sterically hindered quaternary anomeric center, unlike the tertiary anomeric center C-1 of 1,6-anhydro sugars [29][30][31][32][33][43]. Furthermore

• disaccharides were cleaved and acetylated, as shown in Scheme 5. The difficulty of these reactions might have been attributed to the more liable nature of the tertiary acetal center C-1 of fucose as compared to the sterically hindered quaternary ketal functionality C-2 of the 2,7-anhydro skeleton. To our

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• was converted to the desired product 2j. The substrates bearing various R2 substituents, including electron-withdrawing, electron-donating, sterically hindered, and heterocyclic groups, all reacted smoothly and afforded the desired chromone derivatives 2k–v in acceptable to good yields. Furthermore

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• shifted relative to the one of the Z-isomer. Depending on the substitution pattern, the thermal lifetimes of metastable E-isomers at 25 °C vary from hours to days and sometimes even years [12][13][14]. Remarkably, for sterically hindered hemi-indigo derivatives, thermal lifetimes of the metastable states

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• cyclopentanone and ammonia. The polycyclic amine product was then converted into a sterically shielded polycyclic nitroxide. Sterically hindered nitroxides have high chemical stability [5] and can be used as spin labels to study biopolymers in cells [6]. The introduction of spirocyclic moieties has a smaller

• effect on the reduction rates of nitroxides than does the introduction of linear alkyl substituents. However, spirocyclic nitroxides may have much longer spin relaxation times at 70–150 K which make them attractive agents for spin labeling [7][8][9]. Sterically hindered nitroxides can be used as spin

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

• para-substituted aryl bromides, high regioselectivities in favor of the α-arylations were observed. The meta-substituted 3-bromoacetophenone and methyl 3-bromobenzoate also afforded the α-arylated lilolidines 10 and 11 with high regioselectivities. Conversely, with the more sterically hindered aryl

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• 7c. 1,3-Dipolar cycloaddition of nitrones to alkenes is known to be reversible [13][14]. We recently reported a similar reversibility of the intramolecular cyclization of sterically hindered pent-4-enylnitrone of the 2H-imidazole series [15]. Treatment with Zn in an AcOH/EtOH/EDTA/Na2 mixture was

• in the side chain, the hydroxymethyl group in 9a–c was protected via acylation. Heating of 9a–c with an excess of acetic anhydride in chloroform quantitatively afforded the corresponding esters 10a–c. The products of acylation of the sterically hindered amino group were not detected in the reaction

• general synthetic approach to sterically hindered spirocyclic nitroxides based on an intramolecular 1,3-dipolar cycloaddition reaction in alkenylnitrones followed by isoxazolidine ring opening. The resulting asymmetric pyrrolidine nitroxides have unexpectedly high rates of reduction with ascorbate. These

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• 4-phenyl-2-butanol into benzylacetone in only 30 min (Scheme 6, ketone 11b). This protocol was successfully extended to other secondary alcohols to afford the corresponding ketones 11b–19b in high conversions and yields. The oxidation of sterically hindered secondary alcohols such as adamantan-2-ol

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

• this methodology resulted in homocoupling of bromoalkynes. Among the examined Cu(I) and Cu(II) salts, Cu(OTf)2 was proven to be the optimal one. Both EW and EDGs were well tolerated except 2-amino-6-methylpyridine which might be sterically hindered due to methyl group at 6-position. The use of

• EDGs at p- and m-positions gave a higher yield than sterically hindered o-substituents and EWGs. Moreover, the absence of metal leaching as tested by atomic absorption spectroscopy (AAS) demonstrated the heterogeneous nature of the used catalyst. Recently, a robust, ligand and additive-free

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• loading was 0.61 mmol/g. Lower loading of the resin was used in order to enable quantitative incorporation of the sterically hindered, glycosylated building blocks. The synthesis of tri- and pentapeptides (Scheme 1B) was performed manually on solid phase [28]. The obtained glycopeptides were cleaved from

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• [4][5]. Stability and radiochemical improvements were investigated by Matesic et al. [5]. For instance, electron-donating 18F-arylsulfonyl fluoride 1 was >98% stable in the buffer at 3 h, while the electron-withdrawing compound 2 was only 8% stable [5] (Figure 1). The more sterically hindered 18F

• [6]. To further investigate the stability of 18F-sulfonyl fluorides, the sterically hindered compound 4 was selected with enough steric bulk in the 2,6-position. The initial chlorosulfonylation reaction was performed using 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) as a source

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• . The configuration of C-5 in each stereoisomer was established using NOESY experiments and theoretical models. The main limitation of this approach was the impossibility to incorporate both aromatic and sterically hindered amines (e.g., tert-butylamine). Besides the reports of Rivera’s and Ramírez’s