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

• considering the diastereoselectivity observed when enantiopure (S)-α-methylbenzylamine was used as chiral component in the two-step syntheses from amine surrogates [22], we assayed our new strategy to achieve a one-pot diastereoselective synthesis of benzodiazepinones 6 (Scheme 2, Table 2). Interestingly, 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

• , without purification, was treated with caesium carbonate (1 equiv) and heated to reflux for an hour. Gratefully, the dipyrrolopiperazinone derivatives 12 were obtained with high yields and complete diastereoselectivity in an efficient and simple way (Scheme 11, Table 6). The structure of these systems was

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

• phosphine-based ligand (L). This methodology was applied to the alkynol moiety of ethinylestradiol (8) (86% yield), and alkynols derived from ethisterone, levonorgestrel, lynestrenol, and epiandrosterone (epi-ADT), obtaining excellent yields (85–93%) and high diastereoselectivity (dr > 20:1) in all cases. α

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• the total synthesis of saframycin A (5) and jorunnamycin A (103), the application of a non-standard NRPS module to the synthetic substrate analogs realized the rapid construction of an appropriately functionalized complex scaffold in one pot, with precise control of regio- and diastereoselectivity

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

• the 54% and 63% yield, respectively (Table 1, entries 3 and 4). We observed an increase in Norrish II fragmentation in these cases. The observed diastereoselectivity was poor, supporting the radical character of the ring-closing event. A similar trend was observed when studying the methanesulfonyl (Ms

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

• -3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition

• -aza-1,3-butadienes [40][41][42][43][44]. Recently, we have found that the three-component reaction of isoquinolines, dialkyl but-2-ynediaotes and 5,6-unsubstituted 1,4-dihydropyridines afforded functionalized isoquinolino[1,2-f][1,6]naphthyridines in good yields and with high diastereoselectivity via

• diastereoselectivity of the reaction, the concerted addition process is much more likely. However, it is difficult to distinguish between these two reaction processes at present. Conclusion In summary, we investigated the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• , epiandrosterone, hecogenin, rockogenin, and tigogenin. All of them were successfully converted into boronic esters with high diastereoselectivity. In 2021, Cook and co-workers [45] unveiled the photomediated trifluoromethylation of alcohols by converting alcohols into thiocarbonates (Scheme 8). This copper

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• benzophenones 22a,b in moderate yields (Scheme 8) [38]. Again, no trend was observed depending on the structure of the chromones. 1,3-Bis(silyloxy)-1,3-butadienes The reaction of 11a–c with 1,3-bis(silyloxy)-1,3-butadienes 6a–h, catalyzed by Me3SiOTf, afforded products 23a–j with excellent diastereoselectivity

• -(trifluoroacetyl)chromone (14a) with 1,3-bis(silyloxy)-1,3-butadienes proved not to be successful in our hands. However, reaction of 3-(trifluoroacetyl)thiochromone (31) with 1,3-bis(silyloxy)-1,3-butadienes 6a,b, in the presence of Me3SiOTf, afforded products 32a,b with excellent diastereoselectivity (Scheme 16

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• spiropyridazine-benzosultam 3aa with 10% yield and high diastereoselectivity (Table 1, entry 2). Encouraged by this result, we tested several solvents to determine their effect on the [4 + 2] annulation reaction. Acetonitrile showed the best result, providing the highest yield (Table 1, entries 3–7). We also

• was tested, resulting in the expected spiropyridazine-benzosultams 3ab–al in good to excellent yields with high diastereoselectivity. For N-benzoyl hydrazones 2b–g, the electronic effect of R3 group on the [4 + 2] annulation reaction was significant. Electron-withdrawing groups gave relatively higher

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