Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• compounds 7e and 7f, no competition with the NH of the phenylalanine was observed. The corresponding tetrahydropyridazines 7a–f were obtained in moderate to good yields (Scheme 5). Concerning compounds 7e and 7f, each diastereomer of the 1:1 ratio mixture could be isolated after purification by flash silica

• chromatography. With dipeptides 7e and 7f stereoisomerically pure, we next focused our attention on the preparation of novel peptidic structures to perform some conformational analyses. Starting from the methyl ester 7, each diastereomer was engaged in a classical sequence of saponification in the presence of

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• of the aldol product mixture showed that the reaction mixture contained only a negligible amount (1.9% ee) of the anti-isomer 63a and syn-diastereomer 63b was obtained in the racemic form when 60 was used as an organocatalyst. On the other hand, when using 61, both diastereomers were obtained in

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• diastereomers 12 and 13 are often easily separable, and each diastereomer of optically active alcohols or amines can be obtained with an excellent optical purity (reactions 3 and 4 in Scheme 1). To the best of our knowledge, these are the only four works for the preparation of optically active substances having

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• mixture of diastereomers (diastereomer ratio = 1:1) for cross-coupling, and the corresponding compounds 2 and 3 were obtained as mixtures of diastereomers in a certain ratio as estimated by proton and fluorine NMR spectroscopy. Substrate scope for cross-coupling reactions The substrate scope was

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• diastereomers were then subjected to silver nitrate column chromatography to separate the geometric isomers. This separation was only partially achieved (Supporting Information File 1, Figure S10), but one diastereomer was enriched and the sample was subjected to NOESY NMR experiments. Coupling was observed

• between H-5 (4.82 ppm) and C-6-methyl (1.66 ppm) (Supporting Information File 1, Figure S11) for the minor compound eluting earlier in GC, indicating that both hydrogen atoms are close together and that the double bond has a Z-configuration. The other diastereomer showed no coupling between H-5 (4.84 ppm

• ) and C-6-methyl (1.56 ppm) and was assigned as the E-diastereomer. This assignment is further supported by the 13C NMR spectra. The major diastereomer shows C-7 at 39.7 ppm, a typical value for (E)-configured aliphatic chains with allylmethyl groups [29], while the (Z)-isomers show values around 30 ppm

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• one diastereomer of 7q was formed (Scheme 4). This result is in accordance with the calculated mechanism. The more electron-rich trisubstituted alkene 3r reacted directly with Selectfluor leading to a tertiary carbocation which was trapped by acetonitrile in a Ritter-type process to generate bisamide

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• –11). The stereostructure of the products was confirmed by X-ray crystallographic analysis using the minor diastereomer of 3bd, nicely separated from the major isomer by recrystallization, and the major product 4ba. As was our expectation, these compounds [49] possess the anti relationship between the

• . If the in situ conversion of anti,syn-7a to anti,syn-7b follows the above ester alcohol exchange mechanism, employment of dibenzyl malonate should afford a single compound. This is actually the case and the expected dihydrofuran anti,syn-7c was obtained in 53% yield as a 98:2 diastereomer mixture

• . However, the comparison of their specific region of the 13C NMR charts and sharp peaks readily led us to qualitative understanding of the high purity of 11a-D possibly as a single diastereomer (Figure 3). Conclusion As described above, we have succeeded in the facile preparation of 2,3-epoxyesters 2 with

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• /spot [260], affected seedling growth of amaranth and lettuce [261], and exhibited moderate activity against Bacillus subtilis (IC50 value of 50.3 µM) [210] and Staphylococcus aureus (3.6 mm inhibition zone at 250 µg/mL) [138]. The 2-epi diastereomer of altenuene was isolated from Alternaria alternata

• amaranth and lettuce and turned out to be antifungal against Alternaria brassicicola with an MIC value of 125 µg/mL [261]. A further diastereomer 3-epi-altenuene (57) was isolated from Alternaria sp. and was given the name ‘4’-epialtenuene’ [147]. Its structure including the relative configuration was

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• yield (78% vs 96%) was observed upon scaling up. In the case of products with two stereogenic centers (3r–t), the formation of a single trans-diastereomer was observed. According to literature data, the vicinal coupling constants in the 3,4-disubsituted β-lactam cycle have characteristic values for the

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• reaction took place with a α,3-like relative configuration on the major diastereomer, similar to that obtained for the Ugi/Staudinger/aza-Wittig sequence and complementary to that observed for the Ugi/reduction/cyclization sequence (see Supporting Information File 1, Figure S2). With the aim of building

• assayed in our group. Under these conditions, the bis-1,4-benzodiazepines 7 resulting from the reaction of the amino group with the imine on the benzodiazepine were obtained as a single diastereomer. On the basis of the preferred conformation for the 1,4-benzodiazepin-5-ones 5 and 6 [20][22], where the

• single diastereomer (Scheme 5, Table 3), while N-phenylglycine afforded the enamine derivative 10 (Scheme 6, Table 4). Both structures were confirmed by single-crystal X-ray diffraction of compounds 9a and 10a (Figure 2). The diastereoselectivity observed in the hemiaminals and their stability can be

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• activity. Synthesizing spiro heterocyclic steroids entails numerous methodologies. Although the inherent stereochemistry of steroids sometimes facilitates the production of a single diastereomer without the need for chiral auxiliaries, nevertheless, their synthesis remains challenging due to the creation

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• have indicated the unique role of the benzhydryl group for azetidinol reactivity [32][33][34]. To our delight, 3l cleanly underwent ring opening via hemiketal 10 to deliver dioxolane 11 as a single diastereomer in 93% yield (Scheme 3b). With this result at hand, we tested several other carbonyls known

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

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

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• the three-component reaction of methyl propiolate, cinnamaldehyde and arylamines. The results are summarized in Table 3. It should be pointed out that TLC analysis and 1H NMR spectra of the crude products usually indicated that only one diastereomer was predominately produced in the reaction even

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• from bacteria and forms albireticulene (2), a C1 diastereomer of 1 that also features the 2E alkene [7]. Two coral enzymes, BaTC-2 and EcTPS1, were found to form klysimplexin R (3), a 2Z-cis-eunicellane [8][9]. Recently, a third bacterial version, MicA, was identified as producing the 2Z-trans

(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

• with subsequent reduction of the olefin motif respectively. In contrast to the approach of Mykhailiuk, this route yields the exo-1,5-BCHs as the major diastereomer. 1,5-BCH (±)-64 and 1,5-BCH (±)-71 were prepared as bioisosteres of the fungicides fluxapyroxad and boscalid, respectively [45]. Comparison

• planarity. Brown and co-workers prepared the [2]-ladderanes via a multistep sequence from diene 147 including an intramolecular [2 + 2] cycloaddition (to (±)-148) and a Wolff rearrangement (to (±)-150) (Scheme 16A) [63]. This approach yielded predominantly the endo diastereomer of trans-[2]-ladderanes 150

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• separated by 0.21 ppm. In the 13C NMR spectrum of 11a–f, a ≈10 ppm upfield shift for the chloroacetal was seen to δ ≈92 ppm from the C5 acetal present in the starting materials. Only a single diastereomer was formed for all 3,3-disubstituted rearrangement products due to the hindrance on the endo-face, with

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

• IIIa,b led to a lower reaction rate compared to their pyridine counterparts. However, the cis diastereomer (IIIb) showed significantly enhanced enantioselectivity compared to its equivalent pyridine-based ligand with the same configuration (see Supporting Information File 1, part S5). This change from

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• ZnMe2 (entries 9 and 10). This difference can be ascribed to a less favorable homolytic substitution reaction of ZnMe2 in relation to its higher analogues and is in line with previous literature observations [11]. The configuration of the major diastereomer was determined by chemical correlation (Scheme

• concomitant deprotection of the nitrogen and the ester groups. The sample was found to have a negative optical rotation, thereby indicating that the major enantiomer present had S configuration [26]. This allowed to establish that the configuration of the major diastereomer present in (RS)-14b was (RS,S), and

• configuration of the major diastereomer of (RS)-14b. Air-promoted tandem 1,4-addition–aldol condensation reactions of Et2Zn with α-(aminomethyl)acrylates. Diagnostic experiments for a radical mechanism and for enolate formation. Diagnostic experiments with N-benzyl enoate 10. Reactivity manifolds for the air

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

• crystal structure of compound 4k (Figure 1, CCDC 2059918). Though there are four chiral centers in the product structure of the isoquinolino[1,2-f][1,6]naphthyridine, the 1H NMR spectra of the products all showed that only one diastereomer was produced in the reaction, which showed that this reaction has

• ]naphthyridines 4. Because all reactions in this process are retro-equilibrium reactions, the most thermodynamically stable diastereomer is preferentially produced in the reaction. In the absence of isoquinoline, the 5,6-unsubstituted 1,4-dihydropyridine acts as an active enamine, which adds to dimethyl

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• time led to the formation of only one diastereomer, but in a low yield of 11%. Neither the addition of LiCl helped to increase the diastereoselectivity of the reaction (Table 1, entry 8). See Supporting Information File 1, for complete optimization of the reaction conditions. Achieving

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• diastereomers, C3-symmetric (P,P,P/M,M,M)-117 and C1-asymmetric (P,P,M/M,M,P)-117 were separated and each racemic diastereomer was resolved into the enantiomers by chiral HPLC. The CPL spectra of both enantiomers show a maximum centered at 643 nm, a glum value estimated as 3 × 10−4 for (P,P,P/M,M,M)-117. The

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

• 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

• of the etheric oxygen atom and the antibonding orbital of the P=O bond (the stereoelectronic effect), leading to the more stable anti-diastereomer 74 (Scheme 16) [38]. In the phostone 74 was installed a linker 2-(5-aminopentoxy) group via transesterification with benzyl N-(5-hydroxypentyl)carbamate

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

• TMSOTf) promoted trapping gave the aldol adducts 4 in good to excellent diastereoselectivity (up to a single diastereomer), but the yields were relatively low (25–44%). To overcome this limitation, the authors used TMSOTf to prepare and isolate the corresponding silyl enol ethers, which were later

• high diastereoselectivity and good to excellent yields. In most cases, the authors detected only a single diastereomer in the crude reaction mixture (NMR). Using the enantiomeric form of the ligand or the chiral sulfoximine reagent, four diastereomeric β-aminoketones can be produced in excellent

• (Scheme 51B) [94]. Giving only a single diastereomer with good enantioselectivity using a Rh/bicyclo[2.2.2]octane-2,5-diene (bod) complex, a broad variety of spiro compounds were isolated in good to excellent yields. The authors have also shown that this skeleton provides a great opportunity to prepare

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• -stereocenter [32]; a significant downfield shift of this signal (up to 0.5 ppm) could be expected for the diastereomer with the ᴅ-α-stereocenter with respect to the ʟ-isomer. To prove the recyclability of the t-Bu-containing (S)-N-benzylproline-derived ligand L7, the ʟ-(pMeCysNi)L7 complex was decomposed by

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

• investigated the Cu-catalyzed borylacylation of bicyclic alkenes 1 (Scheme 11) [45]. Like the previous borylative difunctionalization reactions, it was found the reaction generated a single exo,exo diastereomer. A brief investigation into an enantioselective variant of the borylacylation was investigated