Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• and proceeds through a by base-promoted annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes

• ylide B. Thirdly, the intermediate C is formed by the nucleophilic substitution of a halide ion in substrate 1 by the allylic ylide B. Then, Michael addition of the amino group to the C=C bond results in the cyclic intermediate D. Finally, the spiro[indoline-3,5'-[1,2]diazepine] 3 is produced by the

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• involvement of azomethine ylide; however, the detailed mechanism has not been elucidated. In this article, we describe the thermal reaction of the La@C2v-C82 anion, activated by one-electron reduction, with benzyl bromide derivatives. Results and Discussion The La@C2v-C82 anion [20] was prepared by chemical

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• -stabilized azomethine ylide; Introduction The 1,3-dipolar cycloaddition of azomethine ylides (AMYs) [1][2][3][4][5][6] is a powerful method for the synthesis of bioactive pyrrolidine-containing compounds and natural product analogs [7][8][9][10][11][12][13][14][15]. AMYs generated from the reaction of

• endo-transition state A to give spirooxindole-pyrrolizidine 17 which spontaneously reacts with another equiv of arylaldehyde to form ylide 18 in the presence of zeolite HY. The second [3 + 2] cycloaddition of 18 with 14a affords product 15a as a major product through an endo-cycloaddition and 15a’ as a

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• under heating, followed by the formation of ylide, N–S bond cleavage, and C–N bond formation along with the release of N2. In 2019, Sun and co-workers introduced an unprecedented method for the synthesis of isothiourea derivatives via the activation of diaryl/alkyl disulfides 47 with N-halosuccinimides

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• -holes. Halogen bonding and σ-holes have been encountered in numerous monovalent and hypervalent iodine-containing compounds, and in 2022 σ-holes were computationally confirmed and quantified in the iodonium ylide subset of hypervalent iodine compounds. In light of this new discovery, this article

• provides an overview of the reactions of iodonium ylides in which halogen bonding has been invoked. Herein, we summarize key discoveries and mechanistic proposals from the early iodonium ylide literature that invoked halogen bonding-type mechanisms, as well as recent reports of reactions between iodonium

• include nucleophile σ-hole selectivity, and how ylide structural modifications and intramolecular halogen bonding (e.g., the ortho-effect) can improve ylide stability or solubility, and alter reaction outcomes. Keywords: electron donor–acceptor complex; halogen bonding; σ-holes; iodonium ylides; ortho

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• ylide; sustainable; Introduction Arylamines are among the most privileged structural motifs appearing in various natural products, and bioactive molecules [1][2] as well as offer widespread applications in pharmaceuticals, agrochemicals, dyes, and materials science [3][4]. Particularly the

• generation of carbene as a reactive intermediate [36][37]. Also, spirocyclic iodonium ylides have been used for radiolabeling techniques [38]. In 2013, Shibata’s research group reported a novel trifluoromethanesulfonyl iodonium ylide for trifluoromethylthiolation of enamines, indoles, and ketoesters

• ) with iodonium ylide 2-(phenyl-λ3-iodaneylidene)cyclohexane-1,3-dione (2a) obtained from 1,3-cyclohexanedione in the presence of copper salts as catalysts. The detailed optimization studies are described in Table 1. Initially, we treated aniline (1a, 0.2 mmol) with iodonium ylide 2a (0.24 mmol) in the

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• and the base the initial direct C–H activation of the ylide 12 gives the copper pyridinium ylide 15. The latter reacts with the diazo compound formed through reaction of hydrazone 13 with the base to give the copper–carbene species 16. Then, the intermediate 16 undergoes a Cu–carbene migratory

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• metathesis as key step in the synthesis of dibenzo[b,f]heteropines. Alkyne–aldehyde metathesis in the synthesis of dibenzo[b,f]heteropines. Hydroarylation of 9-(2-alkynylphenyl)-9H-carbazole derivatives. Oxidative coupling of bisphonium ylide intermediate to give pacharin (13). Preparation of 10,11

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• to other ARO reactions, the catalytic cycle is proposed to begin with the oxidative insertion of the Rh(I) catalyst into the bridgehead C–O bond producing 204. The phosphorus ylide attacks 204 in an SN2’ fashion on the endo face giving the ring-opened 205 as well as regenerating the Rh(I) catalyst

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• . The success of gram-scale reaction and diverse functionalization of isocoumarins demonstrated the synthetic utility of this protocol. Keywords: C–H activation; enaminone; iodonium ylide; isocoumarin; rhodium catalysis; Introduction Isocoumarins are an important structural motif in many naturally

• to couple iodonium ylides with enaminones in a Rh(III)-catalyzed C–H activation/annulation cascade reaction for the rapid construction of isocoumarins (Scheme 1c). Results and Discussion Our initial experiment was performed with enaminone 1a and iodonium ylide 1b in the presence of [Cp*RhCl2]2 (5 mol

• -naphthyl-substituted enaminones were smoothly coupled with iodonium ylide 1b to give the expected isocoumarins 3ra and 3sa in 60% and 78%, respectively. Next, we sought to test the generality of this reaction with respect to iodonium ylides. As outlined in Scheme 3, iodonium ylides featuring dimethyl

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• heterocyclizations. Electrochemical N-ammonium ylide-catalyzed CH-oxidation. Oxidative dimerization of aryl- and alkenylmagnesium compounds catalyzed by quinonediimines. FLP-catalyzed dehydrogenation of N-substituted indolines. Funding This work was supported by the Russian Science Foundation (Grant no. 21-13-00205).

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• . Subsequent decarboxylation of thiazolooxazol-1-one I affords non-stabilized azomethine ylide (AY) for 1,3-dipolar cycloaddition with olefinic oxindole 4a to give spirooxindolepyrrolothiazoles 5 and 7. The endo-TS is more favorable than exo-TS for the 1,3-dipolar cycloaddition to afford the major and minor

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

• colleagues reported in 2000 that the reaction between a Michael acceptor such as diethyl fumarate and a sulfur-ylide, prepared from ethyl 2-diazoacetate and tetrahydro-2H-thiopyran in the presence of Cu(acac)2, yielded triethyl cyclopropane-1,2,3-tricarboxylate in 68% yield (Scheme 1, reaction 1) [10]. The

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

• ) from the reaction of dimethyl 2-(methylamino)benzoylphosphonate (70) and trimethyl phosphite at 105 °C through an ylide intermediate D. The ylide D was generated via deoxygenation of benzoylphosphonate 70 with trimethyl phosphite to form a carbene intermediate B, and trimethyl phosphite nucleophilic

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• 1,3-dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to the stable azomethine ylide – protonated form of Ruhemann's purple (PRP) has been developed. Both 3-substituted and 3,3-disubstituted cyclopropenes reacted with PRP, affording the corresponding bis-spirocyclic 3-azabicyclo[3.1.0]hexane

• and cannot be isolated as individual compounds. At the same time, the reaction of ninhydrin and proline results in the formation of the stable azomethine ylide. This 1,3-dipole demonstrated high reactivity towards diverse cyclopropenes, including parent cyclopropene [22]. Note that the reactions of

• reductive amination/cyclization of enantiopure cis-cyclopropane dicarbonyls [26]. The strategy based on azomethine ylide cycloadditions to cyclopropenes enables ready access to a wide range of spiro-fused 3-azabicyclo[3.1.0]hexanes (Scheme 1a). Inspired by our recent achievements, we have focused on

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

• 2021, Deng et al. showcased an unprecedented iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols 22 with α-imino esters 23 as azomethine ylide precursors to afford azepino[3,4,5-cd]indoles 24 in good yields and with complete regioselectivity and generally excellent

• tolerates a variety of substituents in both 22 and 23. From a mechanistic point of view, the reaction proceeds through a domino azomethine ylide formation/allylation/Pictet–Spengler reaction sequence. Recently, An and Xiao and co-workers disclosed high-yielding syntheses of a wide range of indole-3,4-fused

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

• ozonide formed during the reaction [57]. Consequently, no PPh3 or Me2S was required to obtain the crude aldehyde. Subsequent addition of a Wittig ylide gave access to a cyclopeptide with an α,β-unsaturated ester side chain as a (E/Z) mixture. Unfortunately, this compound contained triphenylphosphine oxide

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• ethyl chloroformate/Et3N, followed by Wittig olefination with an ylide generated from (methoxymethyl)triphenylphosphonium chloride and LDA to give the enol ethers as E/Z mixtures. N-Phenethyl carbamates were obtained from benzaldehydes via Henry reaction with nitromethane, followed by zinc dust

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

• liberated using TBAF to give compound 27 in 97% yield over two steps. The alcohol group in 27 was then oxidized to the corresponding aldehyde under Swern conditions and subsequently subjected to a Wittig reaction with a two-carbon phosphonium ylide reagent. The desired α,β-unsaturated ester 28 was then

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• anti-addition of the sulfoxonium ylide to 52. Hou highlighted that the good diastereoselectivity control for the sulfoxonium ylide addition to acyclic α,β-unsaturated substrates such as 52 observed in their work represented the first example in literature. Hereupon, deprotonation of 53 over LiHMDS

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• was described by Sun et al. [46]. In this method, the catalyst (DHQ)2PYR 42 reacts with tert-butyl 2-bromoacetate, and then an ylide is formed by the base Cs2CO3. After a conjugated addition of this intermediate to the coumarin 43 followed by nucleophilic substitution, the corresponding cyclopropa[c

• deprotonated by a base, affording an ammonium ylide/enolate. Meanwhile, the Re-face attack is favored after interaction of squaramide portion of the catalyst with coumarin. Then, a Michael addition followed by intramolecular cyclization affords the desired product 75, as shown in Scheme 23. An enantioselective

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• Scheme 3 consisting of the following steps: (i) Wittig reaction of 2-bromobenzaldehyde with methyltriphenylphosphonium iodide ylide, (ii) lithiation of the resultant o-bromostyrene with n-BuLi and reaction of the aryl lithium species with ethylene oxide, and (iii) oxidation of the resultant primary

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• plausible mechanism shown in Scheme 14 explains the formation of azomethine ylide B by condensation of isatin with amino acid followed by release of a molecule of CO2 via A. The imine B undergoes 1,3-dipolar cycloaddition with the dipolarophiles 39. The cyclization yields the desired product 40 of the three

• yield from 69% to 84% over the conventional protocol as observed during the study. The explored mechanism in Scheme 16 indicates an in situ anti-azomethine ylide (A) generation (between isatin and primary amine) favored due to steric hindrance in syn-ylide. The crucial step determines the route via

• ylide formation over the expected Strecker degradation. The azomethine ylide trapped by 3-alkenylindole undergoes 1,3-dipolar cycloaddition and led to the cycloadducts 44. 4 Pyrans Pyran is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom with two

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

• : PDFA is available from the reaction of triphenylphosphine with halodifluoroacetate salts such as BrCF2CO2K. It exists as a free-flowing white solid that is not sensitive to air or moisture [33]. Upon heating to 80 °C in N-methylpyrrolidone, the compound decarboxylates and acts as a source of the ylide

• Ph3P+CF2−, which was used for the Wittig olefination of aldehydes and ketones. However, heating PDFA in nonpolar solvents (e.g., xylene at 90 °C) favors the dissociation of the ylide to release difluorocarbene which is able to effect the cyclopropanation of alkenes [34]. Trimethylsilyl

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• ketals. The protection of the C-4 hydroxy group, hydrolysis of the acetonide, and selective tosylation of the 1° alcohol were prerequisites for the generation of the C-5–C-6 bond. To this end, the reaction of 82 with the ylide generated from trimethylsulfonium iodide gave the allylic alcohol 83. The

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• the target compounds required the prior preparation of a panel of variously substituted 1,4-diketones 5. The 1,4-diketones 5 have been prepared either by a Nef reaction [56] from the corresponding nitroenone 3 or a Wittig reaction [57] from 1,2-cyclohexanedione and the corresponding ylide 4 (Scheme 2