(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 50% inhibition concentration of selected CYP450 enzymes (IC50). Cis-2,6-disubstituted [2]-ladderanes Brown and co-workers recently proposed cis-2,6-disubstituted bicyclo[2.2.0]hexanes ([2]-ladderanes) as isosteric replacements for meta-benzenes. An exit vector analysis indicated that the substituent

• . Isomerisation to the desired cis-[2]-ladderanes 150 was achieved through epimerisation of the ester functional group (Scheme 16B) [63]. Transformation of the phenyl group (of 150a) or alkene group (of 150b) into synthetically versatile acid 151 and protected alcohol 152 was achieved by standard chemical

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• boron migration occurred during the hydroboration process of spiroviolene that resulted in the production of a mixture of 1α-hydroxyspiroviolane, 9α- and 9β-hydroxyspiroviolane after oxidation. The assertion of the cis-orientation of the 19- and 20-methyl groups provided further support for the revised

• , respectively. The formation of all three products 9–11 can be explained as follows (Scheme 2A) [28][29][30][31]: Due to the favorable formation of cis-5,5-fused B/C ring system, the borane reagent is preferred to approach the double bond of 1 from the α-face, to give either a secondary 1-organoborane

• suitable for X-ray diffraction [35]. The crystal structure of 13 clearly showed that the 19- and 20-methyl groups are cis-oriented in the D-ring which is consistent with that of spirograterpene A. This structural data reaffirms the revised structure of spiroviolene, and further support the unified

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ][49]. Using liquefied HCl gas, he predominantly obtained cis-30 for the hydrochlorination of 1,2-dimethylcyclohexene (29) (Table 1, entry 1), while solutions of HCl gas in ether favored trans-30 (Table 1, entry 2). A similar study, though with lower selectivities, had been conducted by Fahey earlier

• [8]. In the presence of ammonium salts, a dilute solution of HCl in AcOH resulted in a 7:93 mixture of cis-30 and trans-30 (Table 1, entry 3), whereas an HCl solution in acetyl chloride produced a moderate 73:27 mixture (Table 1, entry 4). Grob also explored other bicyclic substrates such as

• octahydronaphthalene (31) and hexahydroindene 33 (Table 2 and Table 3). However, in the case of compound 31, the cis-selectivity was relatively low (Table 2, entry 1). Recently, Frøyen and Skramstad studied the hydrochlorination of 1,2-disubstituted alkenes with HCl gas (Scheme 6) [50]. Numerous unsuccessful attempts

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• categorized into the CCD subfamily and the 9-cis-epoxycarotenoid dioxygenase (NCED) subfamily. Five enzymes have been identified within the CCD subfamily: CCD1, CCD2, CCD4, CCD7, and CCD8. In animals, CCDs are involved in retinoid biosynthesis. In plants, CCD1 and CCD7 cleave the 9,10-double bond of

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• depends on the relative configuration of the ligand used; cis-configuration of ligand affords the nitroaldols with major enantiomer S- (up to 97% ee), whereas the application of ligands with trans-configuration led to nitroaldols with major R-enantiomer (up to 96% ee). The “proline-type” ligand IV was

• improvement of enantioselectivity and the ee values obtained by its copper(II) complex were satisfactory (75–96%). This phenomenon was more distinct in the case of the application complexes of ligands with cis-trans configuration (Ib vs IIb). Whilst the complex of Ib exhibited only poor enantioselectivity

• , the other afforded the nitroaldols with ee values of 60–90%. Finally, the complexes of ligands with cis-cis configuration (Ic and IIc) were evaluated. These catalyst are the most efficient catalysts, producing nitroaldols with very high enantiomeric purity (approx. 90–95% ee). This finding contrasts

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• unusual methyl modification at the oxygen atom of the typical succinimide ring, a feature not seen in the structurally similar brocaeloid D. Additionally, shentonin A (1) exhibits a cis relationship between H-3 and H-4, as opposed to the trans configuration in brocaeloid D, suggesting a divergent

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• lists of bond lengths and bond angles are given in Tables S1–S4, Supporting Information File 3. Compound 3b had the structure of an O-acylated isomer and possessed an E-s-cis(S,N) conformation relative to the C(l)–C(9) bond (Figure 3). The benzo[b]thiophene fragment was planar, whereas the propionyl

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• for C60 complexation. Bipyridine was also used in fluorescence signal transduction systems to induce a conformational change by coordination stimuli (Figure 15b) [60]. The tweezers-like system 27 is built around a tetrasubstituted cis-anti-cis-perhydroanthracene core functionalized at opposite ends

• undergoes a conformational change resulting in an axial position of the pyrene groups that are now far away and present monomeric emission properties. It should be noted that in both systems, the conformational change from s-trans to s-cis of the bipyridine unit is not directly responsible for the closing

• zinc in the apical position of the porphyrins (Figure 15c). Upon the addition of Pd(II), the two pyridine moieties prefer to coordinate the palladium which leads to a 180° rotation motion and confers a cis-conformation to the system. This motion positions the porphyrin units face-to-face and allows

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• oxocarbenium 7 and 7’ which exists as a stabilized form including an intramolecular stabilizing interaction between the carbocation and the ester carbonyl group. However, in close agreement with Hess and Baldwin’s values found for the rearrangement of cis-1,3-pentadiene [24], this transition state was high in

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• chloroform, while only a few exhibit weak fluorescence in hexane [15]. These nonluminescence characteristics are attributable to the low-energy state of the twisted ICT (TICT) state, which is capable of deactivating the ground state through accessible conical intersections (CIs) [15][134][135][136]. In

• perpendicular to that of the aniline moiety. The calculations indicated the presence of accessible S1/S0 CIs. In the lowest-energy S1/S0 CI geometry, the aniline moiety exhibited a pronounced quinoidal character and the carbon atom directly linked to the butadiene moiety exhibited a conspicuous radical nature

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• ). Efforts to selectively achieve one polymorph, through differentiated crystallization processes, were unsuccessful. When analyzing the molecular structure in both crystals, the cobalt core is hexacoordinated, as expected. The two isothiocyanate ions are oriented cis to each other and trans to the

• coordinating nitrogen of the 1,2,3-triazole units. The nitrogen atoms of the two quinoline moieties are therefore trans to each other. This conformation might be induced by the cobalt precursor Co(NCS)2(py)4, which has already the NCS monodentate ligands cis to each other, as it was not the case for other Co

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the PBE1PBE/6-311+G(2d,p) level of theory using the DFT B3LYP/6-311++G(d,p) optimized geometries (DMSO solution) and applying a multi-standard approach [44]. The calculated shifts of sp2-atoms C-7a, C-4, C-6, C-3, and C-3a in (Z)-8 and the s-cis-conformer (with respect to the C4–N bond) of 9 were

• model showed that (Z)-8 was significantly less stable than the s-cis-conformer of 9 in DMSO solution (ΔG = 7.17 kcal/mol; 298 K, 1 atm). As we proposed, pyrazolopyrimidine 8 undergoes dimerization to produce macrocycle 5 under certain conditions (Scheme 5). The dimerization of 8 was thoroughly studied

Synthesis of 7-azabicyclo[4.3.1]decane ring systems from tricarbonyl(tropone)iron via intramolecular Heck reactions

• Aaron H. Shoemaker,
• Elizabeth A. Foker,
• Elena P. Uttaro,
• Sarah K. Beitel and
• Daniel R. Griffith

Beilstein J. Org. Chem. 2023, 19, 1615–1619, doi:10.3762/bjoc.19.118

• the same substitution pattern as substrate 7 tend to give poor yields in similar intramolecular Heck reactions [20]. Moreover, it was found that substrates on which the halide is cis to an additional methyl substituent (used to forge the ethylidene-substituted polycycle common to many alkaloids) often

• cyclized product 16 in 75% yield. These results suggest that these Heck cyclizations are quite sensitive to the identity of the alkene substituent that is cis to the halogen. We were also interested in engaging vinyl iodide 17 in a 7-exo-trig cyclization to form 18. Z-Iodoalkene 17 appeared to react

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• identifying the investigated enzyme as Nocardia brevicatena epi-isozizaene synthase (NbEIZS). GGPP was not converted, but the incubation with GPP resulted in the production of a complex mixture of monoterpenes including myrcene (14), sylvestrene (15), γ-terpinene (16), cis-sabinene hydrate (17), terpinolene

• (18), linalool (19), cis-p-ment-2-en-1-ol (20), terpinen-4-ol (21) and α-terpineol (22). All these compounds were identified by comparison of their mass spectra to library spectra and of their gas chromatographic retention indices to literature data (Table S5, Supporting Information File 1). This

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• functionalization via the canonical organometallic steps of oxidative addition/reductive elimination was ruled out via catalytic reaction of the macrocyclic Groves-type porphyrin catalyst V, a species that is unable to accommodate the mutual cis-orientation of ligands for metal-centered reductive elimination. The

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

• generate intermediates 2 or 3, where the cis-oriented ligands may reductively eliminate to generate either a functionalized β-dicarbonyl (4, most common) or a substituted arene (5, rare). Interestingly, when the first iodonium ylide was synthesized by Neiland and co-workers in 1957, they also evaluated its

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• carbonyl groups of the urea fragment are observed (Figure 4). Values of spin–spin interaction constants 3JCH equal to 5.3–6.0 Hz indicate the cis-orientation of the vinyl proton and the carbonyl (for 4a, blue) or the carboxyl group (for 5a, red) relative to the double bond [24][25][26]. The values of spin

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

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

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• a high diastereoselectivity. From Figure 1, it can be seen that the three protons and the phenyl group have cis-configuration in the hexahydro-1,6-naphthyridyl ring. During the investigation of the above three-component reaction, we found that the three-component reaction of isoquinoline, dimethyl

• cyclobutenyl ring and the 1,4-dihydropyridyl ring exist on the fused position. The two protons at the bridged position and the phenyl group are cis-configured. From Figure 3 (compound 6f), it can be seen that the fused pyrrole ring and the cyclopentyl ring are butterfly shaped. The unusual feature is that the

• C=C double bond is not located between the two carbon atoms substituted with the methoxycarbonyl groups, but between the methylene carbon atom and one carbon atom connected with an electron-withdrawing methoxycarbonyl group. The aryl group and the neighbouring methoxycarbonyl group are cis

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• azobenzene and ferrocene motifs (Figure 1a). The azobenzene scaffolds play a dual role, both as the engine transforming photoenergy into mechanical motion via trans/cis photoisomerization upon UV light input and as a modulator of the crystalline packing by varying the para-substituent R1, which leads to

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

• to furnish the transient complex 81 which undergoes σ-bond metathesis to give the product 77 and regenerating 78 (Scheme 16b). While speaking regarding the alkenylation, the geometrical isomerism, i.e., the stereoselectivity between the cis- and trans-alkenylation, has not been considered so far

• center of π-complex A via the lone electron pair of the pyridine nitrogen to give 90 which further attacks the π-bond in a cis-manner to give intermediate 91. After protio-depalladation the E-isomer 86 is obtained as major product (Scheme 17b). Remote alkenylation In 2011, a study for weakening the

Bromination of endo-7-norbornene derivatives revisited: failure of a computational NMR method in elucidating the configuration of an organic structure

• Demet Demirci Gültekin,
• Arif Daştan,
• Yavuz Taşkesenligil,
• Cavit Kazaz,
• Yunus Zorlu and
• Metin Balci

Beilstein J. Org. Chem. 2023, 19, 764–770, doi:10.3762/bjoc.19.56

• in terms of neighboring group participation by the bromine atom in the methano bridge (8→9). Thus, backside attack of the bromine atom on C7 in 8 at C2 of the three-membered bromonium ion can lead to the four-membered bromonium ion 9. Attack of bromide ion at C-3 of 9 furnishes the cis-addition

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• reaction with Grubbs 1st generation catalyst in DCM, affording 2-(4-methylphenyl)benzothiophene-fused 2-(benzyloxy)-1-oxa-2-phosphacycloundec-8-ene 2-oxide 35 in 70% yield with a ratio of 2:1 for the generated cis- and trans-double bonds. After Pd-catalyzed hydrogenolysis, it was converted into 2-(4

• intramolecular esterification gave the cyclized products 74 and 75 in 82% yield with a 5:1 ratio of anti/cis diastereomers accompanied by a dimeric byproduct 76 in 2.5% yield. The anti-diastereomer with cis-PhO and Me groups as major product 74 is attributed to the stereoelectronic effect between the n-orbital

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• 50200, Thailand Center of Chemical Innovation for Sustainability (CIS) and School of Science, Mae Fah Luang University, Chiang Rai 57100, Thailand Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai 57100, Thailand 10.3762/bjoc.19.47 Abstract Two new cassane diterpenoids, 14β

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• %) but low trans/cis selectivity (Scheme 11). Organoaluminum reagents (Me3Al, Et3Al) were also compatible with the reaction, however, they gave lower yields than the corresponding organozincs. The authors have also shown that these products are suitable for forming [6,7]-bicyclic adducts. Conjugate

• stereoselective conjugate borylation of cyclobutene 1-carboxyester 175 (Scheme 45A) [87]. As a result, the cis-β-boronyl cyclobutylcarboxyester 176 was prepared on a gram scale with 80% yield and an excellent 99% ee (dr >20:1). Subsequent transformation to the corresponding trifluoroborate salt 177 resulted in a

• silylation/aldol cyclization sequence where the diastereoselectivity of the reaction is determined by the Si nucleophile used [90]. Using Me2PhSiZnX·2LiX in combination with ligand L21 leads to the trans adduct, while Me2PhSiBpin together with L30 provides the cis product. Consequently, the authors have