Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

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

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• homophthalimides 8 [10][11][12]. We reasoned that a similar strategy could be adopted for the preparation of 1,2,4-trisubstituted 1,4-DHIQs 9 if access to their diazo precursors 10 was gained. N-Sulfonyl analogs of compounds 10 have recently been synthesized via an innovative Dimroth rearrangement of 4

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• for carboxylic acids, the carbon source is the carboxyl group. When carboxylic acids were used, the carboxyl moiety was first converted to an isocyanate via Curtius rearrangement [82][83][84][85], then reacted with imidazole to form the carbonylimidazole, and eventually reduced to the methyl moiety

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• enzyme VlmA [18]. This intermediate is hypothesized to be transformed into the azoxy bond-containing intermediate via an intramolecular rearrangement accompanied by a concomitant oxidation [18]. Although the exact mechanisms of azoxy bond formation remain unclear, VlmH and VlmA cooperate to biosynthesize

• the case of azodyrecin biosynthesis. The mechanism for the subsequent rearrangement of the ester intermediate for azoxy bond formation remains unclear; however, the conservation of the two hypothetical proteins Ady6/Ady8 among the biosynthetic gene clusters of valanimycin, KA57-A, and azodyrecins may

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• ) probably undergoes rearrangement, decarboxylation, methylation reaction, and further modification to generate compounds 1 and 2. Conclusion S. sp. KIB-H1544 was isolated from the rhizosphere soil of Datura stramonium L. Two novel diarylcyclopentenones daturamycins A and B and one new p-terphenyl

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• -carboxamides with unprecedented rearrangement of the alkyl group [34] (reaction 4 in Scheme 1). Inspired by these novel reactions and in continuation of our aim to develop domino reactions of electron-deficient alkynes [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50], we have investigated the

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• 2 and subsequent rearrangement to 3 are also discussed. In particular, the latter mechanism was studied using density functional theory (DFT) calculations and it was suggested that the ΔG for the cyclization step of an intermediate enolate anion determines the product selectivity. Results and

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

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• cyclase) act on geranylgeranyl diphosphate (GGDP) to perform regio- and stereoselective cyclizations or skeleton rearrangement reactions via carbocation chemistry to form diverse and versatile carbon skeletons; and ii) multiple post-modification enzymes, most often cytochrome P450s, decorate the carbon

• ]. In the biosynthesis of terpentetriene, GGDP was first cyclized by a class II DTS (Cyc1) that contains a conserved DxDD motif to form terpentedienyl diphosphate (TDP) via a syn-labda-13-en-8-yl+ diphosphate intermediate (Figure 2), which, prior to deprotonation, can be followed by rearrangement to

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• achieved within milliseconds initializing bromine–lithium exchange of bromochloromethane to generate (chloromethyl)lithium. This carbenoid species readily reacts with terpenyl pinacol boronates 17, resulting in the formation of intermediate 18, which undergoes 1,2-anionotropic rearrangement to the

• homologated pinacol boronate 19. As the rearrangement is a much slower process, the reaction mixture is passed through a second reactor at elevated temperature with a residence time of 9 s to allow full conversion to the homologated pinacol boronate 19. This species can then be directly pumped to a second

• rearrangement resulting in the formation of thymol (41) along with its regioisomers 42 and 43. However, using an excess of isopropanol and a relatively low concentration of the organic substrates in scCO2 (5% w/w), thymol (41) is produced in a good yield (72%) and selectivity (92.2%) as shown by GC

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• derivatives of 4-oxo-1,4-dihydropyridine-3-carboxylic acid 2 via Mo(CO)6-mediated rearrangement of methyl 2-(isoxazol-5-yl)-3-oxopropanoates 1 (Scheme 1). Results and Discussion Based on our experience of using isoxazoles in the synthesis of heterocyclic compounds [14][15][16][17][18], we hypothesized that

• rearrangement of methyl 2-(isoxazol-5-yl)-3-oxopropanoates 1. High yield transformations of compound 2 provide easy access to 2,4,6-triaryl-substituted and 1,2,5,6-tetrasubstituted nicotinates. Approaches to the synthesis of alkyl 4-oxo-1,4-dihydropyridine-3-carboxylates. Synthesis of 4-oxo-1,4-dihydropyridine

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• technologies microwave and flow were combined are the Dimroth rearrangement exemplified for the conversion of 1,3-thiazine 3 to the corresponding 3-substituted hydropyrimidine 4 (Scheme 7, reaction 1) [48]. A noteworthy example was recently published by Organ and co-workers [49]. A three-component reaction of

• temperature of the nanostructured particles (Figure 4B). The Claisen rearrangement of the electron-deficient aryl allyl ether 9 was chosen to compare the versatility and performance of inductive heating with conventional and microwave heating (Scheme 8A) [50]. The effectiveness of inductive heating is clearly

• at 110–160 bar to form the O-allyl phenol which was heated in a second reactor to 265 °C where the Claisen rearrangement under near-critical conditions occurred to yield 2-allyl-4,6-difluorophenol (12) in 64% yield. In this example, the two reactors made of steel were heated directly by the external

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

• single diastereomer in high yields. In some cases, indenes were obtained in moderate yields. A plausible mechanism of the observed transformations was proposed which implicates a rare rearrangement of the cyclopropane intermediate as the key step. Dimers 2 bearing alkyl substituents at the nitrogen atom

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• of 7-chloro-4-hydrazinylquinoline as base the triazaoxaspiro system G is formed. Finally, pyrazole 7 is obtained via intramolecular rearrangement of G under thermodynamic control. Further, the solventless treatment of nitrodiene 1 with equimolar amounts of thiols led to the formation of sulfanes 8a–e

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

• synthesized α-phenoxyketones 4 in this reaction. The results showed that instead of benzo[b]furan formation, α-ketol rearrangement of phenoxyketones 4a,f occurred to afford β-phenoxyketones 9a,b in 55–60% yields (Scheme 10). Conclusion We have shown that the main direction of the reaction of bromopropargylic

• experiments. A plausible mechanism for the formation of phenoxyhydroxyketone 4. A plausible mechanism for the formation of diphenoxyketone 5. Examples of representative preparation of phenoxyketones 4. α-Ketol rearrangement of phenoxyketones 4a and 4f. Screening of the conditions for reaction of

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

• stable endocyclic alkene α-pinene by protonation. From the common cationic intermediate species, many rearrangement products can be obtained, some of which derived by the ring opening of the tensioned 4-membered ring (Scheme 4). α-Pinene possesses a more stable endocyclic double bond and therefore tends

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

• catalysis diazo compound 30 delivered 3,4-fused tricyclic indole derivative 32 which underwent spontaneous rearrangement to thermodynamically more stable naphthalene derivative 33 upon standing for a few hours. To the best of our knowledge, this is the only report of catalyst-controlled C3 versus C5

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• ]. Some 4H-3,1-benzothiazines were prepared by intramolecular thia-Michael addition with broad reaction scopes [19]. The rearrangement of 2-isothiocyano triarylmethanes in the presence of AlCl3 were also used for the synthesis 2,4-diaryl-4H-3,1-benzothiazines through aromatic ring transfer [20]. A facile

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

• Phil Servatius Uli Kazmaier Organic Chemistry, Saarland University, Campus C4.2, 66123 Saarbrücken, Germany 10.3762/bjoc.18.19 Abstract A peptide Claisen rearrangement is used as key step to generate a tetrapeptide with a C-terminal double unsaturated side chain. Activation and cyclization give

• , such as histone deacetylases. Keywords: chelated enolate; Claisen rearrangement; HDAC inhibitor; peptide; late stage modification; Introduction Among natural products, peptidic structures have entered the limelight due to their extraordinary biological activities [1]. Often found as secondary

• decided to take advantage of an asymmetric chelate enolate Claisen rearrangement, which should allow the stereoselective generation of the unusual amino acid, depending on the configuration of the chiral allylic alcohol used [41][42]. If a peptide Claisen rearrangement [43][44][45] is carried out with a

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• heating, diazo esters 1 undergo a Wolff rearrangement to generate ethoxycarbonylketenes A by loss of nitrogen. The nucleophilic attack of 2-arylaziridine 2 on the ketene moiety produces zwitterionic intermediates B, in which the aziridinium is opened to form the benzylic carbocation stabilized through the

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• of an unexpected rearrangement this structural assignment was still erroneous, and the correct structure 3 was finally established by X-ray analysis of its chromic acid diester [6]. The patchoulol synthase (PTS) has been purified from plant leaves and shown to convert farnesyl diphosphate (FPP) into

• deprotonated to 6, followed by another reprotonation to F, cyclisation to G and Wagner–Meerwein rearrangement to D, the same final intermediate as suggested by Croteau. This mechanism was supported by feeding experiments with (4R)-[2-14C,4-3H]mevalonic acid (15) that is converted through IPP and DMAPP into FPP

• migration from C to D in Scheme 1A), and a Wagner–Meerwein rearrangement to G. The final steps are identical to those in Akhila’s mechanism (Scheme 2A). This work also reported on a labelling experiment with (2-2H)FPP that was enzymatically converted with PTS with incorporation of deuterium at C2 of 3

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• 4 and 5 are C9 compounds possibly derived from thermal or photochemical rearrangement of compound 3 or another intermediate. The yield of each product was calculated by NMR and verified by isolation (Figure 2). To test the generality of this process with other functional groups, we prepared and

• , affording the heterocycle D, a pathway which should not be base-catalyzed, and thus may be reasonably predominant under appropriate conditions. From heterocycle D, a C–C cleavage would produce the N-formyl product 8 and a re-aromatized C8 heterocyclic byproduct E. Rearrangement to hydroxyindole (F) would

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

• ′-binaphthalenes (BINAMs) from achiral N,N′-binaphthylhydrazines (Scheme 1). In the presence of chiral phosphoric acids (CPA 1), the reaction undergoes a simple [3,3]-sigmatropic rearrangement, giving the corresponding products 2 in good yield (up to 88%) and enantioselectivity (up to 93:7 er). The density

• functional calculations showed that the chiral phosphoric acid proton forms an H-bond with nitrogen atoms of 1 and the phosphate acts as a chiral counterion, resulting in a [3,3]-sigmatropic rearrangement with controlled stereoselectivity [14][41]. In 2017, Tan and co-workers developed an organocatalytic

• type of axially chiral indoles 27 (Scheme 10) bearing aniline groups by direct arylation and rearrangement in moderate to good yields with excellent enantioselectivities of mostly 99% ee (Scheme 9b) [59]. The electronic properties and position of the substituents on the azobenzene ring did not affect

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

• condensation of the sodium salt of methyl 2-mercaptoacetate (3j) with bromoacetaldehyde diethyl acetal (36) in DMF solvent and further oxidation of the sulfide using m-CPBA, followed by Pummerer rearrangement using Ac2O and sodium acetate at 90 °C, which provides compound 37 (Scheme 9). α-Acetoxy sulfide

• ). The other diastereomer 59 remained dissolved in the mother liquor. The treatment of the norephedrine salt 58 with 5 M HCl afforded the enantiopure acid 60, which was further converted to the desired 1,3-oxathiolane-substituted ʟ-menthyl ester 35a. The synthetic use of [1,2]-Brook rearrangement for the

• synthesis of lamivudine (1) and the opposite enantiomer 1a was demonstrated by Han et al. [57]. They carried out the [1,2]-Brook rearrangement of silyl glyoxylate 61 using thiol 3nb as the nucleophile. Under optimized conditions, the reaction of the key intermediate 62 with acetyl chloride in ethanol

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

• , tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades. Keywords: acyloin rearrangement; asymmetric synthesis; iminol rearrangement; ketol rearrangement; tandem reactions

• compounds; or (4) the use of imines (X = NR′′), which lead to more stable α-amino ketones. The α-ketol or α-iminol rearrangement is a synthetic organic tool used for ring expansions and contractions and other isomerizations that is also used in some biological pathways [2][3]. Works featuring these

• catalyst in the presence of a substrate possessing a prochiral migrating group or (2) stereospecifically by means of a chiral α-ketol. As an example of an enantioselective rearrangement, complexes of nickel(II) with a series of chiral 1,2-diaminopropane or pyridineoxazoline ligands were evaluated for their

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• stereocontrolled [1,2]-Stevens rearrangement of dihydromethanodibenzoazocines. Dihydromethanodibenzoazocines are example of strained, methylene-bridged tetrahydroisoquinolines (Figure 2) that have attracted much interest of scientists not only due to their resemblance to isopavines and thus their medicinal