Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• stereoselective reduction (Scheme 8). Among a selection of reagents, Mohapatra found that lithium tri-tert-butoxyaluminum hydride in ethanol at low temperature furnished 71 as a single diastereoisomer in 94% yield. The allylic alcohol moiety was protected as TBDPS ether 73 (92%) and oxidatively cleaved following

• treated with an acid to remove the isopropylidene protection and induce intramolecular cyclization to the 2’,5’-syn-furan 109 in 80% yield. This triol was subjected to excess sodium hydride and tosylating agent, and the mixture was allowed to react for 90 minutes, after which benzyl bromide was added to

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• -bis(trimethylsilyl)acetamide [34], simultaneous tritylation of N9 and the N2 atoms was achieved using 4,4'-dimethoxytrityl chloride in pyridine. The obtained derivative 4 was amenable to nitrile reduction using diisobutylaluminium hydride (DIBAL-H) in dichloromethane at −78 °C, followed by workup with

• (DMTr)), 55.4 & 55.3 (H3CO(DMTr)), 53.88 (H3CO(6)) ppm; ESIMS (m/z): [M + H]+ calcd, 794.3337; found, 794.3321. 7-Formyl-N2,9-bis(4,4'-dimethoxytrityl)-O6-methyl-7-deazaguanine (5). To a cooled solution (–78 °C) of compound 4 (1.00 g, 1.26 mmol) in dichloromethane (8 mL) diisobutylaluminium hydride (1 M

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• process in a continuous-flow reactor. The mechanistic studies indicated that a nickel hydride intermediate generated with C(sp3)–H as the hydride source is involved in this catalytic transformation. The hydronickelation step results in the sterically less hindered vinylnickel intermediate 15-I, which

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• hydride will become exceptionally crucial when its hydrogen atoms are replaced by this special heterocycle, forming a multi-indolyl hetero non-metallide. In contemporary period, the said molecules have earned extensive importance in pharmacology to prevent cancer of a number of human organs, certified by

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• amount of sodium hydride (Table 1). Using a 1:1:1 mixture of 1b/2d/NaH in DMF (c = 1.0 M) at rt, the desired monoalkylated product 3bd was isolated in 55% yield (Table 1, entry 1). By studying the stoichiometry of the reaction, we found easier to use a slight excess of the malonate to reduce the amount

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• . Although other methodologies were available, the authors chose to employ lithium aluminum hydride (LAH) to reduce the substituted anthraquinones 67 to the corresponding anthracenes 68, to obtain very good yields (81–90%) [48]. In 2016, Glöcklhofer and co-workers developed a versatile one-pot procedure for

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• could be converted into N-acetates upon reduction with tributyltin hydride and azobisisobutyronitrile (AIBN), and the N-Cbz groups were removed to liberate the free amino groups during hydrogenolysis over Pd/C [259]. A collection of well-defined COS with defined DP and PA was prepared by AGA [93][157

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we

• electrophiles, while maintaining a high degree of N-1 regioselectivity. Keywords: indazole; N-alkylation; regioselective; sodium hydride; tetrahydrofuran; Introduction Indazole (benzo[c]pyrazole) is an aromatic bicyclic heterocycle and can be viewed as a (bio)isostere of indole [1]. While only a few naturally

• temperature increased from room temperature (≈ 20 °C) to 50 °C (Table 1, entry 21). It was found that the latter variation facilitated the complete consumption of 9 with negligible effect on the regiochemical outcome of the reaction. Gratifyingly, sodium hydride (NaH) demonstrated excellent N-1

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

• -component reaction in which a cobalt-Cp*-catalyzed C–H bond addition afforded complex scaffolds in good yields (Scheme 37B and C) [193]. The authors explained the stereoselectivity by means of a mechanism involving a hydride migration suffering influence of steric effects related not only to the catalyst

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• as precursors of nucleophilic radical species in metal hydride hydrogen atom transfer reactions. This unique reactivity, combined with the wide availability of olefins as starting materials and the success reported in the construction of all-carbon C(sp3) quaternary centers, makes hydroalkylation

• than Pd(II)-catalytic types have also been explored. Pd(II)-catalyzed hydroalkylation reactions The σ-alkylpalladium species formed after a carbon nucleophilic attack on an alkene double bond (Scheme 1) have a marked tendency to undergo a hydride β-elimination process that leads to oxidative coupling

• -substituted β-diketones 2a and 2b (61 and 70% yield, respectively). Notably, the unsaturated carbocycles expected from palladium β-hydride elimination were not observed, indicating that an oxidant was not required in the reaction medium to regenerate the Pd(II) species. Later, deuterium-labeling experiments

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -ribofuranose (30) [48]. The ribose derivative 30 was then reacted with triflic anhydride in the presence of pyridine followed by reaction with adenine in the presence of sodium hydride to afford nucleoside 34. The nucleoside 34 was further reacted with benzoyl chloride to afford the fully protected nucleoside

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• −1; MS (m/z): 724.66. Synthesis of N2,N2,N7,N7,N12,N12-hexaallyl-5,5,10,10,15,15-hexabutyl-10,15-dihydro-5H-diindeno[1,2-a:1',2'-c]fluorene-2,7,12-triamine (3): To a suspension of sodium hydride (132 mg, 5.52 mmol) in dry DMF (5 mL), was added triamine derivative 4 (500 mg, 0.69 mmol) in DMF (5 mL

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

• based on the operating transition states [37][38]. A cyclic transition state is proposed in the reaction with sodium borohydride. In this transition state, the oxygen of the sulfinyl group interacts with the boron atom, facilitating the release of the hydride, directing the attack to the Si-face of the

• imine with (RS,E) configuration. When the reduction is performed with ʟ-selectride, with the poorly coordinating metal hydride, an open transition state operates due to the bulkiness of the isobutyl groups bonded to the boron atom. In this case, the attack of the hydride takes place to the less hindered

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

• in the presence of water, it is selectively converted to the 1,4-addition product instead of undergoing a β-hydride elimination leading to an oxidative Heck product [3][26][35]. In 2005, one month after the very first report of the addition of aryltrifluoroborates to enones by Miyaura [32], the

• -hydride elimination. However, the obtained yields were inconsistent. The usage of Pd(TFA)2 led to a better reproducibility of the results. From the various diphosphine ligands tested, (R,R)-MeDuPhos (L2) was identified as the one leading to the best level of enantioselectivity (up to 99% yield and up to

• protonolysis of the O-bound enolate in the presence of PPh3 that leads to the regeneration of the catalytically active hydroxopalladium species and the addition product (Scheme 8) [43]. The presence of PPh3 ensures the preference of hydrolysis instead of a β-hydride elimination, which would lead to an

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• DDQ and the subsequent abstraction of hydride from the benzylic or allylic position generated a charge-transfer complex 298. The complex 298 formed a tin-containing ate oxocarbenium ion complex 299 with SnBr4, and then rapid C–C bond formation took place to generate the cyclic intermediate 300. The

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• product is then reacted with unprotected thymine which, in the presence of stoichiometric amounts of sodium hydride, results in the epoxide ring opening and the formation of the glycol backbone. The pre-amidite is then phosphitylated yielding the desired GNA-T amidite (Scheme 3). Recently, this simple

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• enantioselective hydrocupration of difluorocyclopropenes in the presence of chiral diphosphine ligands using stoichiometric hydride sources that included polymethylhydrosiloxane (PMHS) and organoboranes (Scheme 35) [79]. Cossy and co-workers have achieved the catalytic asymmetric transfer hydrogenation with

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• –59%) by a final optimized hydride reduction. Both the open tetraamine intermediates and the cyclam derivatives successfully coordinated with AuCl3 to give moderate to excellent yields (50–96%) of the corresponding novel tetra-coordinated N,N,N,N-Au(III) complexes with alternating five- and six

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• hydrogenation [15], through addition of the hydride from triethylsilane to afford 1 after in situ hydrolysis of the triethylsilyloxy bond. HOAt alone does not degrade under these conditions and intermediate 21 has been identified and characterized from the reaction medium although we did not identify 2

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• hydride, known as Schwartz’s reagent [8]. This reduces the amide moiety, giving a complex that can be readily transformed into an imine or iminium cation [9]. It may perhaps be observed without straying too far afield from our primary focus that reduction of amides is actually not a leading use case of

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• functionalized aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers as well as several considerations of the reaction mechanism. Results and Discussion We began our study to optimize the reaction conditions (Table 1). When two equivalents of halothane and sodium hydride (NaH) were treated with phenol (1a) at room

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• elimination (Scheme 1) [35]. The oxazole vinylstannane 24 was prepared from commercially available butyne 21. The tri-n-butyltin hydride addition to 21, followed by Swern oxidation and direct oxazole formation with tosylmethyl isocyanide (TosMIC) gave the fragment 24, which was used immediately for the next

• bromine in acetic acid, and then triethyl phosphite. Next, compound 28 was treated with sodium hydride followed by aldehyde 29 [37] to give (E,E)-dienyl stannane 30 in 50% yield. The key Stille coupling between 30 and vinyl iodide 31, prepared by Takai reaction [38] of phenylacetaldehyde, in presence of

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• hydrolysis. These steps can occur through different pathways; in particular, we considered a single-step intramolecular hydride shift with concomitant C–Au-bond breaking (Figure 5) or a base-mediated deprotonation, followed by Au–C-bond hydrolysis through protodeauration (Figure 6). In the former case, it

• emerged that the 1,2-hydrogen shift in TS7 is quite high in energy (ΔG‡ = 18.5 kcal⋅mol−1) relative to the previous barriers shown in Figure 2. This barrier is also much higher than the traditional 1,2-hydride shift in carbocations, which usually show barriers even under 10 kcal⋅mol−1. It has been

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• triquinane (±)-hirsutene (14) [24] (Scheme 1D). In 2011, the same research group used allenyl diazo compound 38, which was generated from the reaction between aldehyde 37 and p-toluenesulfonehydrazide in the presence of sodium hydride upon heating, to produce diyl 40 [29] (Scheme 2A). The intramolecular

• 2014 and 2017, respectively (Scheme 2B and Scheme 2C). The synthesis of (−)-crinipellin A (15) began with the treatment of hydrazone 42 with sodium hydride under reflux to produce the tetraquinane 46 in 87% yield [30] (Scheme 2B). The authors suggested that the diazo compound 43 formed undergoes an

• upon refluxing in toluene and subsequent epoxidation afforded 51 [32], which was converted to (−)-crinipelline A (15) in two steps. The synthesis of waihoensene (16) commenced with the conversion of aldehyde 52a to the corresponding hydrazone 52b, which was treated with sodium hydride under reflux to

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

• evaluated reduction conditions on a simpler difluorinated hexopyranose analogue. Thus, difluoroglucose 21, easily accessible in 3 steps from levoglucosan (1) [21], was subjected to lithium aluminium hydride (LiAlH4) in THF (Scheme 1a) and difluoroglucitol 22 was isolated in 58% yield. The reaction was