Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• converted into the methyl esters 10 (54%), 11 (52%), and 12 (46%). The benzyl-protecting group was removed hydrogenolytically to give products 13 (85%), 14 (65%), and 15 (99%). The alcohols were then converted to the triflates 16 (28%), 17 (41%), and 18 (63%). We have chosen 3,4,5-trimethoxybenzaldehyde (19

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• 11. It was proposed, that the internal hydrogen bond between the catalyst 11 and the P=O fragment of the protecting group of imine 9 is responsible for the observed high enantioselectivities (76–98% ee). The scope included a wide range of substrates, such as aromatic, heteroaromatic, aliphatic, and α

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• give 1,5-diacyl-5-hydroxypyrazolines 131. Cleavage of the protecting group with potassium carbonate in methanol finally provides the corresponding 5-acyl NH-pyrazoles 132 (Scheme 46) [149]. A novel approach to synthesizing pyrazoles via the initial formation of isoxazoles 138 through (3 + 2

• Sonogashira coupling is conducted under basic conditions, it is important to remove the protecting group with stoichiometric amounts of PTSA in this consecutive three-component synthesis. The process tolerates both electron-rich and electron-poor aryl substituents. However, it is not possible to introduce

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

• protecting group yielded the corresponding hydroxyalkynyl derivative 4. Subsequent Lindlar reduction resulted in the (Z)-alkene and a chemoselective tosylation of the primary alcohol led to the formation of tosylate 5. This intermediate underwent a stereospecific 4-exo cyclization upon exposure to iodine

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

• condensation of 73 and 74, followed by highly-diastereoselective vinylogous Mukaiyama aldol reaction and subsequent protecting group manipulations [81][82][83]. The separately synthesized left and right segments, 72 and 75, were then assembled via Horner–Wadsworth–Emmons (HWE) olefination to give carboxylic

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

• . Key to the successful development of this two-step process is the identification of a benzhydryl-protecting group, which orchestrates the photochemical Norrish–Yang cyclization and facilitates the subsequent ring opening. Keywords: azetidine; Norrish–Yang cyclization; ring-opening reaction; ring

• ). The corresponding protecting group (PG) was thought to control the conformation of the 1,4-biradical 2, which is known to be important for efficient Norrish–Yang cyclizations [27][28]. Furthermore, the PG was deemed crucial for the development of further functionalizations of the azetidinols (vide

• ) protecting group (entries 5–7 in Table 1). When changing to phenyl substitution at the nitrogen, azetidinol 3h was formed in 12% yield with a substantial amount of unselective side reactions (Table 1, entry 8). By introducing an ethyl group (1i), only 27% conversion were achieved, with 2% product formation

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• protecting group afforded the cyclic disaccharide exclusively. Cyclic oligosaccharides up to the trisaccharide were obtained using the monomer with a 2-azido-2-deoxy group. Keywords: cyclic oligosaccharide; electrochemical glycosylation; glucosamine; polyglycosylation; Introduction Electrochemical

• (R3 = Ac, R4 = Bn) were obtained in 13% and 6% yield, respectively. The protecting group R3 of 3-OH was changed from an acetyl to a benzyl group. However, conversion and yield of linear oligosaccharides 9c and 10c decreased, and the corresponding cyclic disaccharide 8c was not obtained at all (Table 1

• , entry 4). The reasons for the lower conversion and yield are unclear. However, the lower yield may stem from the lower stability of glycosylation intermediates with a benzyl protecting group at C-3. In all cases, the major product was 1,6-anhydrosugar 7, which was the intramolecular glycosylation

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• yield (92%) and formed the diol 77, after the removal of the Boc-protecting group, where the prochiral hydroxymethyl groups ultimately paved the way towards the natural products (Scheme 22). Bernhardson and coworkers developed a simple scalable route towards ertugliflozin (80), a C-glycoside containing

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• obtained in 84% yield after silica gel purification. Removal of the Boc protecting group from 6 in the presence of trifluoroacetic acid in DCM at room temperature overnight, followed by cyclisation in boiling pyridine/triethylamine, led to 4-hydroxy-1,4-azaphosphinan-2,4-dione (7) in 84% yield. The free

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• us to try another protecting group for the formyl function, namely arylhydrazone. Thus, reactions of compounds 7a–c with a number of arylhydrazines afforded the corresponding hydrazones 11 which were not isolated and subjected to cyclization under the action of K2CO3 (Scheme 5). In most cases the

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• circumvent this side reaction, we envisioned that a more electron-withdrawing protecting group could reduce the tendency of the starting olefin to oxidation. Therefore, the N-tosylated 2,5-dihydro-1H-pyrrole 1b was evaluated under the same reaction conditions with the same three aryldiazonium salts used

• -nitrophenyl)sulfonyl (2-Ns) as alternative protecting groups of 2,5-dihydro-1H-pyrrole (Scheme 5). Although the results with the 2-Ns protecting group were somewhat disappointing, the results with 4-Ns group were more promising, even with a welcome increase in the enantiomeric ratio in some cases (4dd and 4de

• methanolysis, the hemiaminal ether product 3 is formed. We hypothesize that the enantioselectivity-determining step consists of the migratory insertion of the aryl group bonded to palladium to the pyrroline. The steric effect of the t-Bu group favors the coordination of the pyrroline with the protecting group

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• , ii) HBTU, DIPEA, in DMF, rt, overnight, and iii) trifluoroacetic acid (TFA)/triisopropylsilane (TIPS)/H2O, rt, 1.5–2 h. AA and PG stand for amino acid and protecting group, respectively. All AAs in 1a–c, 2a–c, and 4a–c were protected. Structure of C60–oligo-Lys (5a), C60–oligo-Glu (5b), and C60–oligo

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• then transformed into aldehyde 31 through several protecting group adjustments and the corresponding alcohol and Ley oxidation. After the preparation of 33 using Evans syn-aldol condensation as a critical step, 34 was produced by thioester formation, desilylation, and allylic oxidation. Incubating 34

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• partial conversion of the starting material was observed. We postulated that the presence of two Boc protecting groups on the nitrogen makes the oxidation of the C-centered radical challenging. By using 1o only bearing one protecting group the desired product could be obtained, albeit in only 17% yield

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• sophistication over the past decades. Most known processes, however, are still frequently hampered by lengthy protecting-group strategies and very costly purification procedures derived from the "stop-and-go" synthetic methods (Figure 1a). Those protocols are still far from the ideal synthesis, implying high

• atom efficiency, step and pot economies, decreased number of purification steps, or protecting-group-free synthesis. Multi-step domino [1][2] and one-pot [3] reactions represent a new powerful toolbox in organic synthesis to install molecular complexity economically and sustainably, starting from

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

• -phosphite intermediate was then oxidized with hydrogen peroxide to yield dibenzyl α-phosphate 6, achieving an overall yield of 89% for these two steps. Removal of the 2-(phenylsulfonyl)ethanol protecting group in compound 6 was successfully achieved through treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• applied between the catalytic and lipophilic units to avoid a decrease in the catalytic activity. The demethylated cinchona squaramide 6 was reacted with O-p-toluenesulfonyl-N-Boc-ethanolamine. The protecting group was removed using trifluoroacetic acid, followed by a neutralization step, gaining the

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

• , thereby precluding its synthetic exploitation. Results and Discussion Preparation of α-(aminomethyl)acrylates We commenced our study by preparing a selection of α-(aminomethyl)acrylates with variations of the nitrogen protecting group and the ester substituent. Towards this end, the direct allylation of

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

• intermediate 6.3 (ᴅ- or ʟ-threitol) that was then alkylated with mesityl lipid alcohol to produce 6.4 [80][81]. The acetal protecting group was removed in acidic conditions and then the intermediate 6.5 was subjected to oxidative cleavage to yield an aldehyde that was reduced with NaBH4 to produce 6.6a,b

• 1H-tetrazole to produce the trialkyl phosphite 8.3 that was oxidized with tert-butyl hydroperoxide to produce phosphate 8.4. Then, β-elimination of the cyanoethyl protecting group produced PAF with a global yield of 70%. The limit of this method arises from the instability of the precursor 8.1 for

• deprotonation of solketal in DMF followed by the addition of oleyl alcohol tosylate. 9.3 was isolated after the hydrolysis in acidic conditions of the acetal protecting group. The protection of the primary alcohol required a protecting group that can be deprotected without affecting the C=C double bond of the

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• of the Boc-protecting group with the Teoc group then gave phenol 136. Compound 136 was then subjected to a highly diastereoselective oxidative phenolic coupling giving fused tetracyclic architecture 137. Follow-up acid-mediated intramolecular aza-Michael addition and subsequent alkene reduction

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

• been shown to impart high levels of enantioselectivity for these ketones [46]. We performed the conjugate addition for 2 h and then added imine 58 having a tosyl protecting group. The workup allowed the isolation of domino products 59 as a mixture of diastereomers with dr 3:2 and enantiomeric purities

• several imines bearing various N-protecting groups [48]. We have argued that this protecting group could influence the enolate addition. Indeed, an effect of the nitrogen protecting group was observed. Interestingly, small sulfonyl-based protecting groups led to the (R,R,S)-diastereoisomer of the product

• 61. On the other hand, the sterically bulky diphenylphosphorane group afforded the (R,R,R)-diastereoisomer 63 as the main product. The large protecting group likely overrides the repulsive interaction between the enolate and a phenyl group in a preferred synclinal Mg-bound arrangement of the reagents

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

• -butyldimethylsilyl-protecting group resulted in the corresponding 1,5-enyne only being produced in a 33% yield. Several different norbornene derivatives were explored and gave the anticipated exo,exo-difunctionalized product in good yield. In contrast, when using an ethylene-bridged bicycloalkene to generate the

• ]-sigmatropic rearrangement of the diazabicycle 47 to form the allylic carbazate intermediate 51. Nucleophilic attack of an organomagnesium, or organocuprate, in an anti SN2’ fashion on 52 furnish the final ring-opened product 49. The authors note the use of a carbamate protecting group was crucial for the

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -benzyl group with the Cbz group, trityl ether hydrolysis, oxidation of the liberated OH group, and stereoselective addition of MeMgBr to the resulting aldehyde functionality. Hydrogenolysis of the Cbz protecting group in 13 followed by N-alkylation afforded pyrrolidines 14–16 which after acidic

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

• reaction has never been used in the synthesis of natural products before this report, and no β-elimination of the silyloxy group was observed, although this often occurs in such systems [26]. The installation of the two alkenes in 37 required 13 additional steps, and further protecting group manipulations

• were necessary to give compound 38 as a precursor for the late-stage RCM cyclization. This ring formation was very challenging and necessitated extended optimization. Indeed, during the course of the RCM a dramatic effect of the OH-protecting group on the cyclopentane unit was observed. The presence of

• a TBDPS substituent in compound 40 was assumed unfavorable, since this bulky residue generates a steric hindrance precluding the cyclization (Scheme 6, path A) [27]. Its replacement by a sterically less demanding benzyl protecting group (compound 44) allowed the reaction to occur (Scheme 6, path B