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

• reactions with electrophiles, intramolecular cyclization and disproportionation process. The synthetic viability of the approach will be considered. A one-pot multistep synthetic protocol is suggested, based on addition of thiols to the mixture of isomeric alkenes formed in an electroreductive opening of a

• dominant reaction product formed in the reductive opening of the cyclopropane ring in complex 3 was new derivative 5 containing a five-membered ring (see below and Scheme 2). Intramolecular cyclization The anionic species formed in the ring opening in complex 3 undergo fast intramolecular cyclization via

• ). 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

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• ]. Intermediate A may combine with 1 to produce B, which may react with the EGB or another molecule A to produce C, releasing HCl. In Abushanab’s report [12], C can be coupled with A in a similar manner to yield D [12]. Finally, intramolecular cyclization of D may yield 2. In order to obtain a deeper insight in

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• first reported synthesis of pharmacologically interesting N-thiazolyl derivatives. Keywords: fused-ring systems; hydrazones; indazoles; intramolecular cyclization; N-heterocycles; Introduction 1H-Indazoles are important scaffolds due to the prevalence in compounds with biological activity [1], such as

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

• -methylaminobenzamides 72, 76 and N-methyl-2-(3-bromopropylamino)benzamides 79 via the P–C bond formation as the crucial step. N-(3-Chloropropyl)-2-methylaminobenzamides 72 and 76 and N-methyl-2-(3-bromopropylamino)benzamides 79 were first treated with phosphorus trichloride followed by intramolecular cyclization in the

• ethyl esters and diethyl chlorophosphite (83a, R = EtO) or ethyl N,N-diethylchlorophosphamidite (83b, R = NEt2) followed by an intramolecular cyclization via an intramolecular Arbuzov reaction under heating [35]. The obtained γ-phosphonolactams 85 were further hydrolyzed into 2-(3-phosphonopropyl

• derivatives 83 followed by an intramolecular cyclization via the intramolecular Arbuzov reaction under heating generated 1,2-azaphospholidine 2-oxides 89. Compounds 89 were further transformed into N-phosphoryl- and N-thiophosphoryl-1,2-azaphospholidine 2-oxides 90/2-sulfides 91 via oxidation with hydrogen

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• reaction. So, based on literature reports [53][54][55], we have proposed a reaction mechanism in Figure 5b. Initially, DDQ abstracts a hydride ion from substrate 1a to generate the intermediate A. Then intermediate A undergoes an electrophilic intramolecular cyclization to form the cationic intermediate B

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• heating. This observation explains the formation of side-product 8 in the original Flematti’s synthesis [21] (Scheme 1). With thiopyranthiones 6b, 15b, 16b in hand, we carried out the esterification step with 2-chloropropionyl chloride, followed by intramolecular cyclization which provided the desired

• prepare the desmethyl analogue 26 through esterification of 6b with chloroacetyl chloride followed by intramolecular cyclization stayed unrewarded due to the lack of reactivity in the cyclization step. In order to overcome this problem a new strategy was developed. We combined the synthetic protocol of

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

• directions and result in the formation of an unusual unsymmetrical dibenzoazulenodipyrrole dimer 2 and/or a product of intramolecular cyclization ‒ indene 3. The result of the reaction is determined by the nature of the substituents in the starting DAS molecule. In most cases, dimers 2 were obtained as a

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• -trisubstituted isoxazoles (Figure 1) [21][22]. Similarly, palladium catalysts were used for the electrophilic intramolecular cyclization of alkynes and aldoximes to produce 3,4,5-trisubstituted isoxazoles, but the scope of the substrates of the method was limited as the substituted 2-alkyne-1-one O-methyl oximes

• thermodynamical product. The solvent polarity also affects the keto–enol equilibrium of the intermediate II-D. In polar solvents, the keto tautomer is predominant as an electrophilic group for the intramolecular cyclization, while in nonpolar solvents, the enol tautomer could not accept a nucleophilic attack for

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• )pyrroles [15]. The CsF-promoted nucleophilic addition of isocyanides to bromoacetylenes furnished the functionalized bromovinyl amides followed by Pd-catalyzed formation of 5-iminopyrrolone [16]. Sequential nucleophilic addition/intramolecular cyclization of amidine with bromoacetylenes led to imidazoles

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• ]. Conventional synthetic methods for piperidine derivatives include nucleophilic substitution (route (1) in Scheme 1), reductive amination (route (2)), intramolecular cyclization of amines and alkenes (route (3)), the Diels–Alder reaction and subsequent reduction (route (4)), and the radical cyclization reaction

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• , tetrabutylammonium bromide (3) to act as a competitive guest for the cavity and acetic acid (4) to mimic just the Brønsted acidity of the capsule. Carbonyl–ene intramolecular cyclization of (S)-citronellal to the corresponding diastereoisomeric cyclic secondary alcohols. Dehydration reaction of 1,1-diphenylethanol

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• monoamine product 47 further underwent intramolecular cyclization facilitated by the confinement of the cavitand and produced cyclized urea product 48. In a following work (Figure 13c) [78], the binding dibromide 49 showed rapid tumbling conformation in the cavity of the cavitand host E on the NMR timescale

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

• assigned as 1-alkyl-3,5,5-trimethyl-5,6-dihydro-1H-azepino[4,3,2-cd]indoles 8. The authors proposed that aza-Michael addition of 4-aminoindoles 7 to in situ generated mesityl oxide gives compound 9 which undergoes a regioselective intramolecular cyclization–dehydration sequence to furnish 8. In 2019, Zou

• -cd]indoles 21 from the intramolecular cyclization of Ugi adducts 20 in moderate to good yields and excellent chemo-, regio-, and diastereoselectivity (Scheme 7) [17]. Mechanistically, the reaction involves a tandem gold(I)-catalyzed dearomatization/ipso-cyclization/Michael addition sequence to

• -butyloxycarbonylation and N-alkylation (Scheme 14) [25]. The C5 cyclization regioselectivity and trans-diastereoselectivity were not influenced by the electronic nature of the indole-N-substituent. Conclusion As illustrated by these studies, SEAr-based intramolecular cyclization and annulation reactions of 3,5

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• click products 14 substantiated the hypothesis that the insolubility of Cyl derivatives with short side chains limit their synthetic applicability. The fact that 11 underwent rapid intramolecular cyclization after thiol addition renders further investigations into thiol-ene click-initiated cyclization

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

• of two isomeric 1,2-oxazoles (Scheme 2) [34][35]. In the first route, enaminone 3a–h and hydroxylamine gives intermediate A, which then removes one molecule of dimethylamine to form intermediate B. This is followed by intramolecular cyclization to intermediate C, and subsequent dehydration to

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• desulfoamination or nucleophilic desulfoarylation at position C4, and the following intramolecular cyclization occurs to produce 1,2-naphthoquinones fused with the benzo[a]carbazole or benzo[c]carbazole system (Scheme 17). An interesting reaction for the formation of 4-cyanoethyl-l,2-naphthoquinone from β-NQS−M

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• ring-opened with Br2 and a substoichiometric amount of PBr3, leading to good yields of the corresponding α-bromocarboxylic acids. Subsequent intramolecular cyclization over 1 h using a two-phase system (H2O/CHCl3) containing R4N+OH− afforded α-bromo lactones in good yields. This method can be applied

• successfully synthesized carboxylic acid 2a from lactone 1a in good yield, we next investigated the ring-closing reaction of 2a. Various acids and bases (PTSA, hydrochloric acid, NaOH, KOH, and NaHCO3) were used to promote the intramolecular cyclization of 2a; however, no reaction was observed using any of

• in a dramatically lower yield of 3a (8%), most likely because 3a is unstable to base at room temperature and may decompose or polymerize (see Supporting Information File 1). To avoid decomposition or polymerization, 3a produced in situ by the intramolecular cyclization of 2a should be separated

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

• radical intermediate 137. Subsequently, intramolecular cyclization of 137 generates radical intermediate 138 which then successively undergoes a SET of Fe(III) and deprotonation by t-BuO− to give the annulated product 133a and regenerates the Fe(II) active catalyst. In 2014, the Loh group reported an

• . In the case of activated alkenes, the species will undergo a 7-exo-trig cyclization. On the other hand, it is energetically more favorable for the maleimide species to sequentially undergo a 1,4-HAT, 1,4-HAT, 1,6-HAT and intramolecular cyclization to form the 6-membered ring. Further, by applying

• authors propose the intramolecular cyclization proceeds via the nucleophilic attack of a brominated or cationic benzylic position rather than a radical cyclization. In 2021, Tang and Zhang demonstrated a similar radical annulation of unsaturated carboxylic acids with disulfides for the synthesis of γ

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• )quinolines 1a–f was synthesized via an intramolecular cyclization reaction, in which trifluoromethyl-substituted enamino ketones reacted with concentrated sulfuric acid at adequate temperature (120 °C) and time (10 hours) to furnish the desired compounds, following the method already described in the

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• (see Scheme 1C) [10]. Appropriately 2-functionalized quinazolinones of type 5 might be good starting materials for the intramolecular cyclization providing the target compounds (see Scheme 1D); however, this approach was rarely used [33][34][35][36], possibly due to low regioselectivity of the ring

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• 73. These acted as hemithioacetal substrate and acyl donor, respectively. CAL-B was further utilized for the subsequent intramolecular cyclization of hemithioacetal intermediates 75 and 76. Screening of base additives showed that good results could be obtained by addition of 4-methylmorpholine (74

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• cyclic lactones [69]. The intramolecular cyclization of the acyl radical A gives the tricyclic radical species C, which then forms fluorenone (3) after abstraction of a hydrogen radical by an additional equivalent of the tert-butoxy radical. Conclusion In summary, we have demonstrated that the metal-free

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• previously reported methods is proposed in Scheme 22. Firstly, the hydrocupration of enyne 54 with LCuH 57 provides propargylcopper intermediate 58. The 1,3-isomerization of 58 and the following nitrile addition produces imine intermediate 60, which subsequently undergoes intramolecular cyclization, a 1,5

• -hydrogen shift and σ-bond metathesis with hydrosilane to give the silylated pyrrole product 63 and the LCuH catalyst 57. In addition, the intermediate 58 might go through isomerization to form imine intermediate 64, which undergoes intramolecular cyclization to provide the minor regioisomer 67 (inner cycle

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

• epoxidation protocol was applied to the double bond using (−)-DET to afford chiral oxirane 100 in 85% yield. The free primary alcohol was then protected as tosyl ester 101 and treated with p-TSA to induce intramolecular cyclization. The anticipated furan 95 was successfully isolated in 85% accompanied with

• introduced by the addition of a protected propargyl alcohol to the epoxide derived from triol 109. The furan ring is formed by an acid-catalyzed intramolecular cyclization of the alcohol intermediate obtained from the Noyori reduction of α,β-unsaturated ketone 110. This compound is eventually constructed

• 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

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

• total syntheses of many natural products [34]. Despite its wide application in ring formation reactions, only a few review articles on Hg(II)-salt-mediated cyclization reactions are available in the literature [35]. This review describes the intramolecular cyclization of unsaturated compounds in the

• diastereomers 30a,b and 32a,b was obtained, respectively. trans-Isomers were formed as major products over cis-isomers (Scheme 12) [52]. Five- and six-membered N-containing heterocyclic phosphonates were synthesized by intramolecular cyclization of alkenyl α-aminophosphonates in a similar way with the treatment

• cyclization of γ-hydroxyalkene derivative 187 as an intermediate stage to give a mixture of diastereomeric 2,5-disubstituted tetrahydrofurans 188a and 188b (Scheme 58) [119]. Later for the total synthesis of ventiloquinone J (194), a Hg(II)-salt-catalyzed intramolecular cyclization reaction of the ortho-allyl