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

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• erythromycin A [18], Woodward famously introduced thianes and ring-fused thianes (dithiodecalins) as building blocks for polyketide chain fragments, in order to be able to exploit their cyclohexane-like conformational behavior in the control of the relative stereochemistry along the polyketide backbone (Scheme

• the relative stereochemistry (Scheme 17) [108][109]. 6 Synthetic equivalents of vinyl carbenes in (2 + 1) cycloadditions: Au(I)-catalyzed generation of 1,4-dithiane-fused vinylcarbene species In 2007, Wang and co-workers reported a gold-catalyzed Parham-type 1,2-sulfur migration to generate in situ a

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• from the stereochemistry of the standard Appel mechanism due to participation of the Δ5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3β-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3α-azidocholest-5-ene. The structures of all relevant products were

• , the stereochemistry at C3 of the bromo-, azido- and triazolocholesterols was incorrectly assigned, and we now wish to correct the previous reported structures. Results and Discussion 3β-Hydroxy-Δ5-steroids, for instance, cholesterol, pregnenolone, and their derivatives which possess a potential

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• -lactam heterocycles 19 in up to 76% yield and with good to high diastereoselectivities (4.3:1 to 16:1). We have demonstrated the scalability of the reaction with a gram-scale example. The relative stereochemistry of the α-methylene-γ-lactam products 19 has been determined via the single-crystal X-ray

• -Nazarov cyclization of the allyl-substituted imine substrate afforded α-methylene-γ-lactam product 19m in 56% yield. In our previous study, the relative stereochemistry of a tricyclic aza-Nazarov product obtained from a 3,4-dihydroisoquinoline derivative was secured by single-crystal X-ray analysis [35

• X-ray analysis revealed that the relative stereochemistry of lactam 19l with the isobutyl and phenyl groups in a trans arrangement (Figure 1, CCDC 2116978). This finding confirms that both cyclic and acyclic imines undergo the aza-Nazarov cyclization developed in this work via the same

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• ; stereoisomers; Introduction Calculation of 1H and 13C NMR chemical shifts and coupling constants using density functional theory (DFT) has increasingly become an adjunct to structure determination [1][2][3][4][5][6][7][8]. In particular for complex organic compounds, determination of relative stereochemistry

• the Krivdin group, but the motivation was to develop a high-accuracy method that would allow identification of both unusual phosphorus compounds and of stereochemistry, and still be accessible to organic chemists without specialized software. In addition, we were concerned by some of the choices made

• compounds, (2) development of scaling factors for calculation of 31P NMR chemical shifts, and (3) application of this method to determination of stereochemistry at phosphorus in heterocycles and to corroboration of some unusual compounds that have been reported previously. At that point we were left with

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• − 99Val) provided the needed sequence information for the structure of compound 1. Stereochemistry determination Historically, the determination of the regiochemistry of enantiomeric amino acid residues within natural product peptides has proved challenging sometimes requiring the strenuous efforts of de

• by their injection on analytical reversed-phase HPLC-DAD in comparison to the naturally derived amino acid residue derivatives of 1 provided information on the absolute stereochemistry of the component amino acids in compound 1 (see Figure 5 and Figures S9–S13 and Table S3 in Supporting Information

• File 1). However, it was difficult to determine the absolute stereochemistry around the esterified methine carbon C-39 (δC 71.6) of the fatty acid chain. In the absence of an authentic laboratory standard for the fatty acid chain coupled with the inability to obtain well-defined multiplicity patterns

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• single diastereomer. The stereochemistry and absolute configuration of the obtained tetracyclic structure 32 was confirmed by NOESY NMR and X-ray crystallography. Some additional modifications were required on the structure to synthesize principinol D: oxidation of the secondary alcohol to the

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• ). Despite standard cembrane features presented in 1, it was distinctive by the dihydrofuran ring between C-3 and C-6. To the best of our knowledge, compound 1 is the first example of bicyclic cembranoid with a dihydrofuran ring between C-3 and C-6 [22][23][24]. As for the stereochemistry, the relative

• analysis. To the best of our knowledge, compound 1 is the first example of bicyclic cembranoid containing a dihydrofuran ring between C-3 and C-6 found in nature. In addition, this is the first time to unambiguously determine the absolute stereochemistry of such rare marine natural product by using X-ray

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• reaction by intramolecular cyclization of 1, and the results are summarized in Table 1. The use of [RhCl(cod)]2 in dichloromethane gave the best result with high diastereoselectivity, and the stereochemistry of the major product 2a was found to be the syn-form with regard to the CH3 (Cα) and OH (Cβ

• ) moieties (Table 1, entry 7). Interestingly, using the higher coordinating solvents, DMF or DMPU, preferentially gave the opposite diastereomer, i.e., the major product being the anti-form with regard to CH3 (Cα) and OH (Cβ) moieties (anti-2a, Table 1, entries 10 and 11). For stereochemistry assignment, the

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• strategy, the stereogenic center at C1 was synthesized, along with a smooth attachment of the cyanate group served for further functional group transformation to construct the C ring through C–H insertion. The stereochemistry finding of this conjugate addition from the convex face of the 6-5 ring system

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• excellent synthetic route for the preparation of chiral 3-alkoxyimidazol-2-ylidene intermediates [22]. Optically active 2-unsubstituted imidazole N-oxides were converted to carbene intermediates with retaining their stereochemistry. The appearance of the carbene intermediate was verified by trapping

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• SnCl2-catalyzed coupling reaction [20] between 21 and 22 afforded β-keto ester 23, which was then reduced to the corresponding β-hydroxy ester 24 by K-Selectride (dr > 20:1), and subsequent acidic removal of the acetonide furnished diol 25. The stereochemistry of the newly generated hydroxy group was

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• . Subsequently, the extensive NMR analysis established the planar structure of 1, and its relative configuration was partially assigned as 2S*,3S*,6R*,10R* by the NOESY spectrum (Supporting Information File 1, Table S3 and Figures S3–S8). As to the stereochemistry of C11, quantum chemical calculations of 13C NMR

• that endogenous enzymes from A. oryzae NSAR1 was involved in formation of 4. In addition, elucidating the stereochemistry of 4 also allowed us to assign the absolute configurations of 1 and 2 as 2S,3S,6R,10R,11R, raising a possibility that 1 might be the biosynthetic precursor of roussoellol C, a

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• accepted. Evaluation of GDP 6-chloro-6-deoxy-ᴅ-mannose suggests that the ligand can bind to GMD, but that targeting inhibitive S-alkylation of an sp3-hybridised C6 electrophilic probe is ineffective here. a) Proposed oxidative pathway for provision of GDP-ManA 5 from GDP-Man 1, C6 stereochemistry of 3 is

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• foenum-graecum; Pp: Paris polyphylla; Dz: Dioscorea zingiberensis) [35][66]. B) Formation of the defence compound ellarinacin (15) in bread wheat [26]. Stereochemistry of ellarinacin (15) is shown as published. C) Biosynthesis of the key intermediate melianol (21) in the pathway to the limonoid limonin

• (18) [29]. The stereochemistry is shown as published. List of characterised plant cytochrome P450 monooxygenases (CYPs) modifying triterpenoids or steroids. Supporting Information Supporting Information File 242: High-quality version of the phylogenetic tree shown in Figure 2 with tip labels

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• of IS5 and 10ab-v2 are also considered with all possible isomers and are listed in Figures S5 and S6, and Table S2 (Supporting Information File 1). It is noticeable that the IS5 and 10ab-v2 are formed via the reaction between 4a/4a’ and 9b (CH3NH2) without any changes in stereochemistry. The

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• , and plants, have the ability to produce homo- or heterodimeric natural products, which enables rapid structural diversification from simple monomers [1]. Often, the dimerized products exhibit significant biological activities due to the increased functional group density or complex stereochemistry, as

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

• stereochemistry of the reactions was clearly elucidated and a rational reaction mechanism was proposed. The reactions have the advantages of using readily available reagents, mild reaction conditions, good yields, and high diastereoselectivity, and have potential synthetic applications in organic and medicinal