Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• determined the stereoselectivity of the reaction arises from the unattractive interactions imposed from the sterically hindered endo-face of the bicyclic alkene. The mechanistic insights gained from this combined experimental and theoretical study will facilitate further future methodology development in

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• sterically hindered active site (comparison shown with black arrows – Figure 5C and Figure 5D), which in turn conferred selectivity towards the neuraminidase. From the analogues perspective, the absence of TcTS inhibition could be also attributed to the lack of flexibility of the substituents rather than

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• sterically hindered tertiary alkyl bromides, the authors were able to favor intermolecular radical addition of the generated alkyl radical 17 to the vinylcyclopropane, outcompeting radical rebound to an aryl Fe species. The incipient radical can then undergo ring-opening of the cyclopropane 18. Work by

• reaction. In the same year, the Gutierrez Lab reported the first three-component 1,2-dicarbofunctionalzation of alkenes 21 (Scheme 5) [66]. The authors noted π-systems bearing O- and S-heteroatoms had little to no compatibility with the transformation as well as sterically hindered Grignard reagents 2

• radical 28 (Scheme 5). Regioselective Giese addition to the π-system 21 would generate the transient 2° alkyl radical 29. Due to the high energetic barrier associated with direct cross-coupling between sterically hindered 3° alkyl radicals and aryliron complexes, it is assumed the persistent aryliron

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• this case, the nitroalkene could not be activated by hydrogen bonding via the (thio)urea moiety, however, it is also probably less sterically hindered (Figure 3a). The DFT calculated transition states support this analysis. The transition state TS-major-re-SR-cat leading to the major stereoisomer of

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• 39%, respectively), which was presumably due to their lower nucleophilicity. However, the reaction of 2a with more sterically hindered 2,6-lutidine was very sluggish and only trace amount of product 4h could be observed under the optimized conditions over 24 h. Conclusion In summary, we have

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• hydroxylation of positions next to heteroatoms leads to hemiaminals and hemiacetals which typically promotes an overoxidation to the corresponding carbonyl compound. The sterically hindered catalyst Mn(CF3PDP)(MeCN)2(SbF6)2 (where CF3PDP is 1,1′-bis((5-(2,6-bis(trifluoromethyl)phenyl)pyridin-2-yl)methyl)-2,2

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• the A-ring system were the most reactive sites for hydrogen abstraction, yielding fluorinated steroids 4a and 4b in 32% and 23% yield, respectively. For both products, α-fluorination was dominant over β-fluorination, likely because α-fluorination occurred on the less sterically hindered face

• was observed at the less sterically hindered benzylic position. The proposed reaction mechanism for radiofluorination is depicted in Figure 2. Although the trans-difluoro-substituted Mn(IV) complex is the reactive F-transfer intermediate in 19F chemistry, the formation of a trans-18F-difluoro

• adjacent carbamate group. The naturally available substrate 9b was shown to undergo the azidation process at the less sterically hindered position. An analogue of rasagiline (Azilect®), a Parkinson’s disease drug, successfully underwent benzylic azidation, providing product 11c. Other complex molecules

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• products was achieved using β-methyl-substituted, long-chain heptyl-substituted, and sterically hindered cyclohexyl-substituted azides. The α-bromo-β-phenylacroleins bearing electron-donating or electron-withdrawing substituents produced the corresponding trisubstituted 3 in good to moderate yield

• sterically hindered 1-(2-bromophenyl)-1,2,3-triazole derivatives 130. The target compounds, triazolo[1,5-a]indolones 131, were then obtained from 130 in high yield using catalytic amounts of Pd(OAc)2 and PCy3, carbon monoxide, and potassium carbonate and with heating in toluene at 120 °C. The structure of

• such as cinnamyl, (ethoxycarbonyl)methyl, 1-naphthalenemethyl, and (phenylthio)methyl were cyclized with ethynylstibanes 82 and diaryl diselenides 84 to afford the desired triazole products. The reaction between ethynylstibane, organic azide, and a range of diaryl diselenides 84 including sterically

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• posthumously in 1919 [35]. In 1894, Guareschi reported the first high-yield synthesis and the structure elucidation of triacetonamine (6, Scheme 3) [35][36][37], the sterically hindered amine that is the starting material for the synthesis of the popular oxidant TEMPO [38]. Triacetonamine had first been

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• generated, taking place a diastereoselective nucleophilic dichloromethylation of the imine. The addition took place almost exclusively to the Re face of the imine (RS)-14, which is the less sterically hindered in the most stable s-cis conformation (see Scheme 2). The second intramolecular N-alkylation step

• stereochemical outcome of the cyclization considering that the stereoinduction is derived from the dipole–dipole repulsion of the sulfinyl imine, which places the tert-butyl group on the Si face, and thus the cycloaddition occurs from the less sterically hindered Re face. The cyclization process worked also in

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• addition reaction of phenylboronic acid to 3-methyl-2-cyclohexenone and affording the product in a low yield and moderate enantioselectivity (36%; 85% ee; Scheme 26) [20]. Palladium-based catalysis provides better results in this area. Up to now, asymmetric addition reactions to sterically hindered enones

• . Thus, palladium-based catalysts represent a more suitable alternative to the widely used rhodium complexes for these sterically hindered enone derivatives. Synthesis of optically pure 4-phenylchroman-2-one [34]. Synthesis of (R)-tolterodine [3]. Catalytic cycle of the Pd(II)-catalysed 1,4-addition of

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• State University, 23 Gagarin Ave, 603950, Nizhny Novgorod, Russia 10.3762/bjoc.17.26 Abstract The fused 1,3-dithiole spacer seems to be very suitable for the functionalization of sterically hindered o-quinones with additional groups capable of coordination of metal ions and/or possessing a redox

• activity. An effective method for the synthesis of sterically hindered o-quinones containing 1,3-diketonate, dinitrile and p-quinone-methide functional groups at the periphery of the ligand has been developed. The novel compounds have rigid and conjugated structures and exhibit properties typical of o

• annulation of sterically hindered o-quinones with a 2-substituted 1,3-dithiole cycle seems to be a promising tool for the preparation of redox-active dioxolene species bearing additional functionalities. The previously described o-quinones with an annulated 1,3-dithiole fragment display a remarkable

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• [80], compound (Z)-(+)-143a delivered the bromodiene (Z,Z)-(+)-145a in good yield and stereoselectivity. Isomerization of (Z)-(+)-143a to (E)-(+)-143b was carried out successfully using sterically hindered base DBU or DABCO. Treatment of (E)-(+)-143b with 144 using the boron-Wittig reaction [79

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• providing a mixture of monoprotected diols (−)-53 and 54 in a 10:1 ratio for the least sterically hindered alcohol in 98% yield. After chromatographic separation, (−)-53 underwent radical-induced Barton–McCombie deoxygenation (AIBN, Bu3SnH) to form (−)-55 in 82% yield. The double deprotection of (−)-55

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• sterically hindered DICAB, compared to the liquid DIPAB, but that a too high reaction temperature such as 60 °C tends to increase the degradation pathways instead of the formation of the desired compound. However, this effect was not observed when performing the reaction in MTBE. A high yield of 86% was

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• approach, however, seems less attractive as it requires an additional step for the proper modification of the starting material. An alternative, more appealing method would capitalize on the in situ generation of a less sterically hindered, and therefore more reactive electrophilic nitronate. As we have

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• retention of configuration was unexpected since the fluoride anion would have to approach the more sterically hindered β-face. To account for the retention of configuration (minor product) in the fluorination of compound 13, we proposed the involvement of an oxiranium-like intermediate A (Figure 3b

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• reaction yielded the racemic product after purification. Scheme 3 is showing that the induction of stereochemistry of the Diels–Alder reaction depends on the chirality at the chiral ligand and not at the helix. This allows improvement of the stereoselectivity by using more appropriate sterically hindered

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• been noticed from the literature that the construction of these types of sterically hindered tetrasubstituted alkenes is really difficult through McMurry coupling reaction or by other means (Scheme 14). 2.2 Functionalization at benzene ring(s) bay positions In another event, the Sakuria group has also

Efficient [(NHC)Au(NTf₂)]-catalyzed hydrohydrazidation of terminal and internal alkynes

• Maximillian Heidrich and
• Herbert Plenio

Beilstein J. Org. Chem. 2020, 16, 2080–2086, doi:10.3762/bjoc.16.175

• even when using aryl-, alkylacetylenes, or electronically different aryl groups in tolanes. However, the steric bulk of a single methyl group in 2-methyltolane led to the selective formation of the single addition product 7h, but even such sterically hindered tolanes (synthesized via Sonogashira

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• structure with accessible minor groove at variance to poly(dG-dC)2, which has sterically hindered minor grooves by amino groups, and poly(A)-poly(U) is an A-helix with major groove available for binding of bulky small molecules [38]. The interactions of the NDI derivatives 3a,b, and 5 with DNA/RNA were

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