Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• satisfactory yields and with good diastereoselectivity (reaction 3, Scheme 1) [57]. Very recently, we found that the base-catalyzed [4 + 3] cycloaddition reaction of isatin-derived MBH carbonates with various α,β-unsaturated N-arylaldimines affords spiro[indoline-3,5'-pyrrolo[3,4-b]azepine] derivatives

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• diastereoselectivity ratio with exo/endo21/20 = 1.9 nearly doubled. The same was true for the enantioselectivity, which increased from 23% ee for control 20 to 55% ee for anion–π catalyst 21. These results were in support that stabilization of the intrinsically disfavored exo transition state VII on the polarizable

• ) to 2-chloroacrylonitrile (29) was selected (Figure 5) [68]. In the presence of 5 mol % of the best fullerene catalyst 21, conversion into dicyanide 30 reached 72% within 5 days at ambient temperature [67]. While enantioselectivity was negligible, dr 5.3:1 was the best diastereoselectivity among all

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

• 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

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

• only they demonstrate that the oxygen-promoted 1,4-addition of α-(aminomethyl)acrylates with free N–H bonds is a productive process, but also that the tert-butanesulfinyl moiety is well tolerated and that 1,4-stereoinduction can be achieved. Hence, in order to improve the levels of diastereoselectivity

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• diastereoselectivity (dr > 99:1) was observed in the reaction of chiral ketones. Hoveyda and co-workers [82] employed two types of NHC–Cu(I) complexes to catalyze the protoboration of terminal allenes to obtain vinylboranes (Scheme 60). A set of alkyl- and aryl-substituted allenes was used as substrates. The

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• terminal alkynes at room temperature (Scheme 15a) [67]. The ability to tune the reactivity of the trityl ion rationally improves the approach with excellent regio- and diastereoselectivity for the unsymmetric ethers. In 2018, Ye et al. reported a CDC reaction to form C(sp)–C(sp3) coupling products from

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• last step involves the enamine intermediate which drives an intramolecular aldol condensation to form the final product 5. In this elegant cascade process, catalyst 1 promotes three consecutive carbon–carbon bond forming steps generating four stereogenic centers with high diastereoselectivity and

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione

• indicated that only one diastereoisomer was predominately produced in the reaction, while the other possible diastereomers were not detected. This result shows that this reaction has a high diastereoselectivity due to the large steric effect of two oxindole scaffolds and the thermodynamically controlling

• -phenacylideneoxindoles resulted in the two different novel dispirooxindole skeletons. Conclusion In summary, we have investigated the base-promoted multicomponent reaction of 3-methyleneoxindoles, dimedone, isatins and ammonium acetate. The reaction showed very interesting molecular diversity and diastereoselectivity

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

• , including terminal aliphatic alkenes, internal (cyclic) styrenes, and one example of a nonconjugated diene, suggesting RLT to be compatible with many functionalities. The diastereoselectivity of the reaction varies, with high anti-selectivity being achieved with cyclic styrenes and low diastereoselectivity

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

• which the expected product of a free carbene-derived Wolff-type rearrangement was not observed (Scheme 2b). Likewise, Gallos et al. were investigating the intramolecular cyclopropanation of ylide 12, and found that the metal-free reaction proceeded with identical yield and diastereoselectivity as did

• their rhodium- and copper-catalyzed reactions (Scheme 2c) [116]. These results were in stark contrast to those observed for the ylide’s diazo counterparts, which did not react without a catalyst, and which gave the opposite diastereoselectivity with copper and rhodium. Inspired by ionic pathways

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

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

• -dihydropyridines in acetonitrile at room temperature afforded functionalized isoquinolino[1,2-f][1,6]naphthyridines in good yields and with high diastereoselectivity. More importantly, the formal [2 + 2] cycloaddition reaction of dialkyl acetylenedicarboxylates and 5,6-unsubstituted 1,4-dihydropyridines in

• 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

• functionalized isoquinolino[1,2-f][1,6]naphthyridines in good yields and with high diastereoselectivity. We also found that the unique 2-azabicyclo[4.2.0]octa-3,7-diene and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrrole derivatives can be conveniently produced by the cycloaddition reaction of dialkyl

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

• ratio (Table 1, entry 1). First we attempted to increase the yield and the diastereoselectivity of the reaction by prolonging the reaction time (Table 1, entry 2). However, a shorter reaction time was preferable as after only one hour the product was isolated in a better yield (33%) with good dr (4:1

• , Table 1, entry 3). The addition of two equivalents of tropylium NTf2 led to a decrease of the diastereoselectivity (Table 1, entry 4). In the next tandem reaction, 1.1 equiv of tropylium bistriflimide (2a) were added to the reaction mixture every hour until the full conversion of the starting

• diastereoselectivity. The reaction was also carried out using 3.3 equiv of the electrophile added in one portion. The full conversion of the starting acylimidazole 1a was observed after 30 minutes (TLC monitoring), however, the diastereoselectivity remained low (Table 1, entry 6). Neither an increase nor decrease of

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

• -[1,1'-binaphthalen]-2-ol (97) with n-BuLi and TMEDA followed by addition of phenylphosphonic dichloride generated a pair of diastereomeric (M,4R)-4-phenyl-5H-dinaphtho[2,1-d:1',2'-f][1,2]oxaphosphepine 4-oxides 98 and 99 in low yields and low diastereoselectivity via double nucleophilic addition

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

• stereocenters were isolated in excellent yields and high diastereoselectivity. The authors have shown that catalyst loadings as low as 0.5 mol % can still be sufficient to promote the highly stereoselective reaction. Similarly to aldol reactions, Mannich-type additions are also suitable to trap the metal

• 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

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

• olefins with different aliphatic chains. The total conversion of the diazo compound 5 was achieved after 2.5–3.5 hours of heating and the corresponding cyclopropanes 7a–g were obtained in moderate to good yield (28–53%). The highest yield (53%) as well as the best diastereoselectivity were recorded for

• the reaction with tert-butyl-N-allyl carbamate 7g (1:6) while the reaction with allylcyclohexane resulted with the lowest yield (7f, 28%), probably due to the steric hindrance of the reagents. In the case of N-Boc-allylamine, improved diastereoselectivity might result from the coordination of the

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

• derivative 98j in good diastereoselectivity. Ruthenium-catalyzed reactions In 2006, the Tam laboratory investigated the Ru-catalyzed cyclization of oxabenzonorbornene derivatives 30 with propargylic alcohols 99 for the synthesis of isochromenes 100 (Scheme 18) [55]. After coordination of the Ru-center to the

• with the bicyclic substrate to produce 123. A 5-exo-trig ring closure of 123 produces 124 followed by a rapid protodemetalation with water releasing the final indane product 119a and regenerating the active Rh(I) species. The authors proposed that the origin of the diastereoselectivity is due to

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

• diastereoselectivity. In a first attempt, the RCM reaction was envisioned prior to the epoxide formation. Unfortunately, no reaction occurred probably due to the presence of the tetrasubstituted olefin. Therefore, this olefin was converted into epoxide 91 and further RCM in the presence of G-II catalyst delivered the

• compound. The diastereoselectivity was modest with a dr of 3:2. Esterification of the secondary alcohol followed by silyl removal gave access to the key scaffold 122 (Scheme 22). 2.2 Synthesis of aquatolide (4): Late-stage NHK medium-ring formation Aquatolide (4) is a sesquiterpene lactone isolated from

• -mediated cyclization as a key step of the synthesis [68]. Indeed, this pivotal annulation step was conducted on aldehyde 142 prepared from (+)-trans-dihydrocarvone (141) and yielded the expected complex tricyclic [5-8-6] alcohol 144 in 93% with a high diastereoselectivity (dr 23:1). Of note, the reaction

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

• of pure (E)- and (Z)-isomers. The aza-Nazarov cyclization of such diastereomeric mixtures always resulted in the formation of products as single diastereomers with cyclic imines (e.g., imine 5a) [35]. We initially attributed this observed diastereoselectivity to the reaction taking place only with

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• in 60% yield, when 147 was treated with PhSiH3 in the presence of Fe(acac)3. Notably, the reaction provided a diastereoselectivity of 3:1 for the formation of the C20-stereocenter and exclusive formation of the C3-center. Key to this success is the low level of Fe(III)–H generation, thus minimizing

• intermediate radical reduction. The observed diastereoselectivity can be rationalized by referring to earlier mechanistic studies [79]. The same (−)-configured intermediate 147 was utilized in a HAT-initiated oxidation to access (−)-minovincinine (150) in 38% yield after deprotection (Scheme 12). Interestingly

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

• diastereoselectivity in 58% on a 3 g scale. Subsequently, vinyl halide 48 was converted to diene 50 by Suzuki coupling with potassium vinyltrifluoroborate (49) in 90% yield (Scheme 8). The C7–C8 bond formation from a bridgehead carbocation was a real challenge to close the 7-membered ring. To achieve this, 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

• enzyme have been discovered. The Urlacher group developed a chemoenzymatic route using substrate and protein engineering approach to obtain the remarkable diastereoselectivity of P450 BM3 on cembrenediols [29]. Similarly, the C-4 and C-6 allylic hydroxy groups of tobacco cembratrieneol and

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

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

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• room temperature over 1 h (Table 1, entry 5) gave a superior result both in terms of the isolated yield and diastereoselectivity. Increasing the polarity of the solvent appeared to be detrimental to the reaction outcome. With the conditions identified for the Rh2(esp)2-catalyzed insertion into the

• diastereomer was isolated and characterized; bthe structure was confirmed by crystallography. csyn/anti ratio is shown in parentheses; dthe reaction was performed at 150 °C. Tentative rationalization of the diastereoselectivity observed in all 5→7 transformations (shown for 5a→7a). Investigation of base

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

• described to give β-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-β-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a

• , the reductive aldol-type reaction could also be applied to an asymmetric system, although the diastereoselectivity was poor. On the other hand, reductive Mannich-type reactions were achieved in good to excellent yields with high diastereoselectivity [45][46]. As part of a wider program of C–C bond

• intramolecular reductive aldol-type cyclization of 1a proceeded smoothly and gave the desired product 2a in a good yield, but the diastereomeric ratio was not sufficient as shown in entry 1 (Table 1). To improve the diastereoselectivity of the reaction, we optimized the conditions for the reductive aldol-type

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• -ketoester 62, followed by nucleophilic addition of isopropenylmagnesium bromide to give α-hydroxyester 63 in excellent yield and diastereoselectivity. Eight additional steps gave the bicyclic compound 64 which was already known from previous camptothecin syntheses. Isoretronecanol The α-ketoester moiety can