A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• insertion of carbenes derived from diazo arylidene succinimides (DAS) into the O–H bond of phenols is described. The initial adducts underwent a thermally promoted Claisen rearrangement followed by DABCO-catalyzed intramolecular 5-exo-trig oxa-Michael addition. Keywords: Claisen rearrangement; diazo

• arylidene succinimides; intramolecular oxa-Michael addition; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocycles undoubtedly occupy a special place in drug design [1] and, in general, spirocyclic compounds intended for the interrogation of biological targets have been associated with

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• the 6-5-5 tricyclic skeleton includes the mediation of Nagata reagent for constructing the C1 all-carbon quaternary centers and gold-catalyzed cyclopentenone synthesis through C–H insertion. Keywords: aberrarone; C–H insertion; gold; Pauson–Khand; total synthesis; Introduction Marine natural

• one quaternary carbon stereocenter and 1,2-dikeone moiety, Nazarov cyclization [33] of 7 was proposed for synthesizing this challenging moiety. The corresponding precursor cyclopentenone 8 may be prepared from alkynone 9 through a gold-catalyzed C–H insertion [34]. Alkynone 9 could be achieved through

• strategy, the stereogenic center at C1 was synthesized, along with a smooth attachment of the cyanate group served for further functional group transformation to construct the C ring through C–H insertion. The stereochemistry finding of this conjugate addition from the convex face of the 6-5 ring system

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• , examples of carbon nitride materials linked together via phosphorus atoms are limited, likely due to challenges in controlling the insertion of phosphorus atoms as linkers under high energy conditions. Mechanochemistry [9][10][11][12] has proven to be effective for the synthesis of a variety of polymers

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• ). Notably, insertion of the second COOR group in the starting cyclopropane complex 4 completely suppresses this reaction channel: intramolecular cyclization of the anions formed in the reductive cleavage of the three-membered ring was not observed. This may be attributed to the decreased nucleophilicity as

• nucleophilic functionalization of the double bond of the dehydroalanine derivatives formed after the reductive ring opening and subsequent protonation. Such an approach opens a route to double functionalization of the amino acids side chain. Insertion of the sulfur-containing fragments is of special interest

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• method to synthesize 1,2-azaphospholidine 2-oxide derivatives 13. Arylphosphinyl azides generate arylphosphinyl nitrenes under photoirradiation. The phosphinyl nitrenes underwent an intramolecular insertion into the ortho C–H bond of the aryl group accompanied with the Curtius-like rearrangement as well

• [24]. Both monomesityl and dimesitylphosphinyl azides 14 generated 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 15 in 31% and 20%, respectively, via an intramolecular nitrene C–H insertion, for dimesitylphosphinyl azide (14b), with 51% yield of phosphonamidate 16 as byproduct. Bis(2,4,6

• 105 via the copper-catalyzed intramolecular carbene aromatic C–H bond insertion (Scheme 20) [44]. This is an efficient synthetic strategy for 3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 through the formation of the C–C bond neighboring at the ring phosphorus atom. Synthesis

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• Tyr224 to form a tyrosyl radical, which abstracts a hydrogen atom from C21 of fumitremorgin B to generate a radical intermediate. The insertion of molecular oxygen at C21 produces a C21 peroxyl radical intermediate, which then reacts with the C26–C27 double bond on another prenyl group to generate the

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• method for the preparation of this class of compounds [2] and showed that DAS can undergo Rh(II)-catalyzed insertion reactions into the heteroatom–H bonds [3]. In 2020, it was shown that under Rh(II) catalysis, DAS can enter insertion reactions into the C–O bond of ethers [4], a rare transformation for

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• intramolecular transformation [14], the insertion of a boron atom into chiral oxindoles is scarcely reported. Continuing with such previous project, next we looked at the copper-mediated reaction of isatin-derived, optically pure sulfinyl ketimines with bis(pinacolato)diboron, as a potential way to access

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• indole derivative 31 in 82% yield (Scheme 11) [22]. Being a kinetically very active catalyst, Rh2(OAc)4 favored the formation of the five-membered ring. On the other hand, employment of Pd(OAc)2-catalysis switched the regioselectivity of this C–H insertion reaction. More specifically, under Pd(OAc)2

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

• regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C–H bond, insertion of the olefin into the iridium

• previously put forth by Nishimura and co-workers [64]. Isomerization of the oxabicyclic starting material to 17 may operate through a similar process described at Hill and co-workers (Scheme 1) [61]. Irreversible C–O insertion of the chloroiridium(I) species at the more electron-dense C1-position affords an

• . Interestingly, C1-substitution with a trimethylsilyl (TMS) group resulted in the corresponding adduct 15k as well as the ring-opened 2,4-substituted naphthol product 16k. It was noted the insertion of a methylene unit at the C1-position allowed for electron-withdrawing substituents to be present in the reaction

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• widely used as building blocks to prepare various heterocyclic peptides [17][18][19][20][21][22]. In particular, 1,2-oxazole amino acid derivatives, such as compounds V [20], VI [21], and VII, VIII [22], can be easily synthesized and are suitable for insertion with the corresponding heterocycle into a

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• I which after coordination and subsequent NCTS insertion is transformed to intermadiate II. β-Elimination finally delivers the required product (Scheme 14). Later, Deb and co-workers developed a methodology towards the synthesis of N-(2-cyanoaryl)-7-azaindoles using [RuCl2(p-cymene)]2/AgOTf/NaOAc as

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

• the initiation of a multistep reaction is through the generation of an organoiron species. This can occur by the oxidative insertion of a low-valent iron into a C–X bond (Scheme 2). Evidently, iron in low oxidation states may operate as an iron-centered nucleophile, and catalyze reactions involving

• initiated, the reaction will propagate, which typically involves the insertion of a π-system (carbometallation of alkenes/alkynes) in the case of organoiron species (Scheme 2). Alternatively, the generated radical species may undergo radical addition to alkenes, alkynes, or aromatic arenes. The final step

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• elimination as opposed to styrenyl selectivity. In addition, the methacrylates were used as allyl surrogates to overcome the reactivity problem caused by steric hindrance of 1,1,-disubstituted alkenes, and the electron-withdrawing esters enhance the migratory insertion to form palladacycle I-2. The CPA

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• with diverse biological activities [17]. The key step first involved the rhodium carbenoid-mediated OH insertion/Claisen rearrangement following complexation of diazoester 56 and allylic alcohol 57 to produce intermediate 58 (Figure 13). Addition of BF3·OEt2 to the reaction mixture then catalyzed the α

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• the nucleophile to the carbonyl site, while in the latter case insertion of the vinyl unit between the carbonyl and the aryl ring makes the electrophilic site in the enaminone significantly less crowded. Cyclization of enaminones bearing heteroaromatic substituents proceeded very well (Table 2

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• insertion and then oxidation (Scheme 54). This methodology was later successfully utilized for the total synthesis of raloxifene and benzo[b]thiophene derivatives [115]. Cyclization involving allenes (>C=C=C<) Hg(II) triflate salts had also been successfully employed for the arylallene 181 cyclization by

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

• same time, the in situ-generated nickel(0) complex 21-VI combines with the benzylic radical 21-III, followed by CO2 insertion resulting in the nickel(I) carboxylate complex 21-VIII. The ketyl radical is deprotonated by the base, and then undergoes a SET with nickel(I) carboxylate complex 21-VIII to

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

• obtaining diaryl sulfides [117]. Selenides Along with the oxygen insertion, Black et al. also performed the oxidative selenium insertion into the C-7 position of highly electrophilic 2-methylindole derivative 184. The dual role of selenium dioxide consists of activation of the C-7 position giving the

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

• glycosidic bond formation. Control over the polysaccharide length (degree of polymerization, DP) and regioselective insertion of modifications or branches are additional challenges. Three main approaches are available (Figure 1): A) enzymatic polymerization [10][11][12][13][14][15][16][17], B) chemical

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

• physicochemical properties of a compound, thus affecting its pharmacodynamic and pharmacokinetic profile. Consequently, fluorination methods are particularly useful in the synthesis of bioactive substances, including marketed drugs (24 and 25) (Scheme 10A) [93]. In addition to oxygen insertion, vanadium use has

• , and the introduction of methyl groups has an attractive effect on the properties of medicinal compounds [135]. However, the selective late-stage methylation has a limited scope due to the lack of suitable methodologies [136]. The insertion of methyl groups at positions adjacent to heteroatoms often

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• siRNA had better eGFP gene silencing activity compared to the control siRNA with a single 2’-OMe RNA monomer near the 5’-end [77]. Conversion of the primary amine on the aminopropyl modification into a tertiary amine (monomer 36) and insertion four times in a 16-mer ON (two in the middle and one near

• also tested for the duplex forming capabilities. Here it was observed that this modification positioned at the 5’-end in a poly-T ON stabilized the duplex (+3.0 °C relative to the control ON) whereas a central insertion of modification 67 or 68 had a neutral or slightly negative effect on the Tm value

• synthesis and coupling efficiency on the synthesizer, significant loss of the hydrocarbon-linked group was observed during the alkaline deprotection conditions [115]. After insertion into a 19-mer DNA-ON, modification 79 did not show any significant increase in Tm. This trend was changed when the

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

• ). Based on additional mechanistic investigations, it was proposed that substrate 23 forms five-membered manganacycle complex 23A under basic conditions, which undergoes alkyne insertion to provide seven-membered manganacycle complex 23B (Figure 7). Subsequently, intermediate 23B undergoes β-bromo

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116