Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• iodonium salts [9], which usually occurs with the retention of the stereochemistry of the vinylating agents (Scheme 1a). Nonetheless, this approach is not necessarily suited for the stereoselective preparation of densely substituted N-vinylazoles because preparing the requisite multisubstituted vinylating

• agents, preferably with well-defined stereochemistry, is a nontrivial task. The addition of azoles to alkynes represents an alternative approach to N-vinylazoles. For example, Nolan and co-workers recently reported a gold-catalyzed addition of azoles to alkynes (hydroazolation; Scheme 1b) [10]. The gold

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

• Abstract We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal

• cyclization mechanism of spiroviolene. Keywords: boron migration; diterpene; spiroviolene; stereochemistry; Introduction Terpenes represent one of the most fascinating families of natural products due to their structural complexity and diversity, as well as their indispensable biological functions that

• stereoselective process to form complex terpene skeletons, normally with multiple stereocenters. In this context, the 3D-defined cyclization products retain the rich information of the complex cyclization process. Thus, assignment of the stereochemistry of the terpene skeleton with high confidence is crucial for

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• investigations into the kinetics and stereochemistry of hydrochlorination reactions. However, both aspects are highly dependent on the reaction conditions and substrates, and no general conclusions could be drawn [3][4][5][6][7][8][9]. Research activity in this field remained relatively dormant until the early

• by the British Oxygen Cooperation in 1956 [47]. In 2012, Carreira reported the hydrochlorination of alkene 27, yielding racemic (±)- gomerone C (28) [48]. Grob observed that the stereochemistry of hydrochlorination reactions can be significantly influenced by the solvent or temperature (Table 1) [9

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• Streptomyces sp. JA74 [86]. Maniwamycin E (43) [87] was also discovered from this strain as a metabolite for which production is enhanced by high-temperature culture. These substances have an azoxy structure, which is relatively rare in the natural environment [88]. The stereochemistry of dihydromaniwamycin E

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• GGPP, followed by hydrolysis by acid phosphatase. GC–MS analysis revealed that AsCPS synthesizes the same product to ObCPS_11g (see Supporting Information File 1, Figure S4A and B). It should be noted that the stereochemistry of CPP needs further verification due to the lack of chiral resolution of our

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• )-ʟ-alaninamide) derivatives [5]. In addition, a combination of NOESY and bioinformatics analyses proposed all three stereocenters of 4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid as S configured [5]. The stereochemistry of these moieties in 3–5 are discussed in the next section, regarding the

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

• underscore the paramount importance of the stereochemistry at position 2 in chiral ligands dictating enantioselectivity. This study provides essential insights for the design of asymmetric catalysts, especially for Henry and aldol reactions. The structure of newly designed ligands I–IV. Plausible transition

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

• from the known brocaeloid D by the addition of a methyl group, and there is a change in the relative stereochemistry at C2 and C3. In addition, the conversion of the five-membered pyrrole ring in compound 2 to the six-membered piperidine ring in compound 1 is intriguing. Although there have been many

• 1 and those previously reported. This suggests that the formation of the quinoline ring in compound 1 may represent a new and unreported biosynthetic pathway. Moreover, to address the low yields that hindered the determination of absolute stereochemistry, we attempted to boost the production of

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

• an achiral diamine (1,12-diaminododecane or DAD) that binds to both Zn–porphyrins and sets them further apart, a higher CD signal intensity is obtained making it a sensitive probe for determining the absolute stereochemistry of chiral carboxylates directly, without the need for derivatization. More

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• the presence of a new compound designated KR21-0001A (1). The structure was elucidated by NMR, and the absolute stereochemistry was determined by advanced Marfey’s method. The results indicated that 1 is a new analog of dihydroxybenzoic acid. 1 has no antimicrobial activity against bacteria and fungi

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• – unguisin J (1) – along with known unguisin B (2) were isolated from a solid culture of Aspergillus heteromorphus CBS 117.55. The structure of compound 1 was elucidated by extensive 1D and 2D NMR spectroscopic analysis including HSQC, HMBC, COSY, and 2D NOESY as well as HRESIMS. The stereochemistry of 1 and

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• obtained in 98% yield with 20% ee after 12 h (Table 1, entry 1). Then, the effect of steric hindrance of the CPA catalyst and solvents on the stereochemistry of this transfer hydrogenation were investigated in detail. Among various 3,3’-disubstituted CPA catalysts (Table 1, entries 2–6), chiral phosphoric

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

• -based decarboxylative [3 + 2] cycloadditions of N–H-type AMYs B3 and B4 for double cycloadditions. The stereochemistry of the cycloadditions and the combination of the cycloaddition with other transformations to be one-pot or stepwise reactions are also presented. Perspective One-step synthesis of

• the R2 group. The stereochemistry of products 10 and 11 was confirmed by X-ray crystal structure and the 1H NMR analysis of both the major and minor diastereomers [69]. The first cycloaddition gives adducts 12 and 12’ as a diastereomeric mixture. At the second cycloaddition, both major and minor

• diastereoselectivity is caused by the different R2/R2’ and R3/R3’groups which no longer have the same stereochemistry as that shown in Scheme 8. Double cycloadditions for bis[spirooxindole-pyrrolizidine] compounds After completing the pseudo-five-component double cycloaddition reactions leading to polycyclic

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• stereochemistry of H14. In TS_2a–3a, the C10 secondary carbocation is stabilized and sandwiched between the two π orbitals of C2=C3 and C14=C15. The status of this orbital interaction is depicted in Figure 3B. This interaction forms the C2–C10 bond and the reaction proceeds to IM3a. Regarding the 4-membered ring

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• correspond, for instance, to biosynthesized intermediates (e.g., 1-O-alkyl-glycerol-3-phosphate [4], lyso-PAF [5]) or neutral ether lipids (e.g., diacyl ether glycerol [6]). Ether glycerolipids are present in mammalian but also in anaerobic bacteria [7], archea (with an inverted stereochemistry at the sn-2

• mild conditions the benzylation of the alcohol function to yield 7.3. Then, the removing of the tosyl group required a two-step sequence. First, 7.3 reacted with cesium acetate and then the resulting ester was reduced with LiAlH4 to produce 7.4 with control of its stereochemistry. Very recently, a new

• sn-2 position and a sn-3 phosphocholine moiety. The length of the saturated lipid chain is composed by either 16 or 18 carbon atoms in the backbone and the stereochemistry of the carbon atom in sn-2 position can be racemic or stereocontrolled. Edelfosine was first synthesized by G. Kny in 1969 [115

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

• starting from both cyclic and acyclic alkyl bromides. The findings of the reaction’s stereochemistry and observations made during some cyclization or ring-opening reactions indicated that the C–H alkylation may proceed through a radical-type mechanism. Next, in 2013, Wang and co-workers [52] reported a

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

• temperatures yielding mixtures of addition products. The structural elucidations of the formed compounds were achieved by NMR spectroscopy. Particularly, the γ-gauche effect and long-range couplings were instrumental in assigning the stereochemistry of the adducts. However, in a recent paper, Novitskiy and

• connectivity of the atoms in the molecule, appropriate 1D and 2D experiments and a variety of other considerations such as coupling constants, their dependence on dihedral angles, as well as through-space interactions (e.g., the nuclear Overhauser effect) help elucidate the correct stereochemistry and

• configurational assignment of organic compounds. The experimental NMR data (13C NMR chemical shifts) are compared with those predicted for all possible theoretical stereoisomers. The correct stereochemistry may be obtained by combining the computed and experimental data [1]. Recently, Novitskiy and Kutateladze

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

• activation of aryl pyrazoles, followed by the asymmetric conjugate addition to the Michael acceptor. Then, the formed cobalt enolate participates in the intermolecular aldol reaction with an aldehyde 207. The stereochemistry of this tandem procedure is controlled by the chiral Co(III) complex C4 bearing

• were able to isolate product (+)-214 in good yield (75–85%) and excellent stereoselectivity (>95%) on a multigram scale. Additionally, both stereoisomers are available by simply using the ligand with the opposite stereochemistry. Pleuromutilin-based antibiotics are an essential line of defense in the

• by the trapping of the metal enolate with Vilsmeier–Haack reagent. This way, the β-chloroaldehyde 143 was isolated in 69% yield and 92% ee. Further transformation of this compound resulted in the taxol core in only 4 steps with 11% overall yield while retaining the correct stereochemistry introduced

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• stereochemistry of the main isomer, the 19F,1H-HOESY NMR spectrum of compound 6c was recorded. The spectrum shows direct correlation of one fluorine nucleus of the difluoromethyl phosphonate group with two cyclopropane protons at 1.75 and 2.91 ppm, respectively. Thus, it is conceivable that the major

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

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• spectra compared to those of a 50:50 mixture of diastereoisomers, obtained from the addition of allylmagnesium bromide onto the corresponding aldehyde). The stereochemistry of the resulting secondary alcohol was expected to be (R) according to Krische's studies involving (S)- SEGPHOS [22]. This result was

• PMB group, in presence of DDQ under anhydrous conditions [18], gratifyingly afforded acetal 25 in 74% yield, whose stereochemical assignment by NOESY NMR experiment showed the syn stereochemistry of the acetal. By deduction, it was confirmed that the asymmetric boron aldol reaction between 8 and 15

• -citronellene (10). Synthesis of fragment 8 from ʟ-cysteine ethyl ester hydrochloride (16). Synthesis of fragment 21 through a stereoselective aldol reaction. 1,3-Anti-diastereoselective reduction of 21 with PNBz transposition, and final determination of the relative stereochemistry by NOESY experiment on 25

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• obtained in the combretastatin D-1 spectrum with the appropriate chiral epoxides, the authors assigned the absolute stereochemistry of the epoxide ring as 3R,4S. This attribution was controversial and was only definitively established years later, as will be shown in this review. In 2005, Vongvanich and co

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• –Hiyama–Kishi (NHK) reaction is an interesting coupling reaction involving the addition of a halogeno derivative (either bromide or iodide) to an aldehyde in the presence of nickel and chromium salts, typically NiCl2/CrCl2, generating an alcohol. In its original version, the stereochemistry of the adduct

• -mediated polyterpene cyclization mechanism, they proposed a rapid 9-step strategy starting from abundant monoterpene farnesol (164), chemically converted into cyclopentanol 165 bearing a trichloroketone function that is a well-known radical precursor. The authors found that the correct stereochemistry of

• inspired by Corey’s work [83] and formed this key function through the addition of propargylborane 181 to aldehyde 180, with a good 80% yield. Protection of the obtained alcohol was also necessary. All these 7 first steps set the stereochemistry of the methyl group on the further eight-membered ring and

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• compound numbers indicate the stereochemistry at C-4 in the cadinane system (Scheme 2) in the following discussion. Secondly, unreacted starting material 18 was not separable from the products by column chromatography. Therefore, maleic anhydride was added at the end of the reaction to form a Diels–Alder

• both the synthetic R- and S-samples would confirm the stereochemistry (Figure 6). The coinjection of A with of R-14 showed only one peak with increased intensity, while two peaks were observed with S-14. Therefore, the natural compound A is (1R,4R,4aR,8aS)-4-isopropyl-1,6-dimethyl-1,2,3,4,4a,7,8,8a

• mass spectrometric and gas chromatographic data to be acquired, clarifying the identity and stereochemistry of several cadinols. Calling male Hyperolius cinnamomeoventris with exposed vocal sac carrying the yellow gular gland. Figure 1 was reprinted from [2], I. Starnberger et al., “Take time to smell

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• reactions thus appears as an appealing tool for the synthesis of insect pheromones, which often display linear chains involving C=C unsaturations with a well-defined stereochemistry (Scheme 1). Therefore, we aimed at developing this strategy for the design of high-scale, eco-friendly and economic new

• , whereas when the reaction was performed in THF alone (at 20 °C), the yield improved significantly (92%, Scheme 3). The efficient iron-mediated alkylation of dienyl phosphates, proceeding with an excellent retention of stereochemistry, was then successfully used in the introduction of the alkyl–alkenyl

• -mediated cross-coupling procedure. We demonstrated that the alkyl–dienyl cross coupling of those solutions of 1-bromopenta-1,3-diene with α,ω-difunctionalized Grignard reagents afforded the coupling product 4 with an excellent 94% yield and a total retention of stereochemistry (Scheme 6). Overall, sex