BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -alkylene-linkers, the diastereoselectivity decreases with increasing linker length (79/33/12% de for C3/C6/C12-linkers, respectively). This is in line with an expected localization of the macrocycle around the ester functionality due to weak [C–H···O] interactions from the COOCH2 group to the macrocycle

• unit (12, used in both enantiomeric forms) or two BINOL units (26) were used for the construction of the rotaxane. The subsequent rhodium-catalyzed polymerization gave the corresponding polymers 32 in high yields of 89–98%. Here, the BINOL-based macrocycle is localized at the ammonium functionality of

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• anion binding property and potent electrophilic activation ability [31][32][33][34][35][36]. To incorporate extra functionality, tertiary amine groups can be also embedded as Lewis base sites for realizing electrophilic/nucleophilic cooperative catalysis [37][38][39]. For this purpose, one kind of

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• amide functionality [13][14][15][16][17][18][24][25]. At the same time, norbornadiene derivatives are available from metalated substrates. Hence, norbornadiene is deprotonated with the Schlosser base and subsequently trapped by an appropriate electrophile [26][27]. In addition, halogenated norbornadiene

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• ring-closure step have been routinely employed for the construction of diverse arene- and heteroarene-fused rings (Scheme 1A) [1][2][3]. In most of these approaches, the new CAr–C bond is formed ortho to the tether/directing functionality on an aromatic or a heteroaromatic ring, as the geometrical

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• the reaction ortho-iodo derivatives with an amino or alcohol functionality showed higher yields than the corresponding iodo derivatives with same substitutions in meta and para position due to the ortho directing effect. They then also analyzed the chance of applying the FeCl2(bdmd) catalyst for the

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• solvents (Table 1, entries 16–20) were explored but were not as efficient in the reaction, producing mixtures of 15b and 17. The scope of the reaction was expanded to include different C1-substituted OBDs to investigate the electronic and steric effects of the C1 functionality on the hydroacylation

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• should undergo a wide range of addition reactions. Ozonolysis, on the other hand, should generate a carbonyl functionality. Radical additions towards the double unsaturated side chain of the Cyl-1 derivative might also allow cyclizations. To get access to the desired double unsaturated cyclopeptide, we

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• repeated cadaverine–succinic acid motifs terminated by a hydroxamic acid functionality, were elucidated by NMR and negative MS/MS experiments. Compounds 1–3 were inactive against bacteria and a yeast but displayed cytotoxicity against 3Y1 rat embryonic fibroblasts and P388 murine leukemia cells at GI50 in

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• eventually brought about the need for newly designed and improved anti-HIV drugs with respect to their improved pharmacological properties [20]. With an idea to keep the presence of azide functionality and to introduce structural rigidity, Marquez et al. [21] developed a methodology for the synthesis of

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• H-7 to C-9, H-8 to C-6, and H-10 to C-8, thus completing an alkyl chain part. The remaining atomic composition was CHO2, and despite the lack of evidentiary HMBC correlations, placing a carboxylic acid functionality at the open end (C-2) was reasonable in consideration of the chemical shift of the

• molecular formula was determined to be C18H22N2O3 based on its NMR and HR–ESI–TOFMS data (m/z 313.1556 [M – H]–, Δ – 0.2 mmu), corresponding to nine degrees of unsaturation. The UV spectrum, exhibiting the absorption maxima at 229 and 282 nm, was typical of an indole functionality. The IR absorption bands

• , and two amino protons. The remaining OH group should be a part of a carboxylic acid functionality considering the lack of oxygenated carbons besides carbonyls, and two degrees of unsaturation, not accounted for by double bonds, were consistent with the indole ring. As expected, assembling the above

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• late. Introduced by Tietze, cascade reactions are sequences of transformations where subsequent transformations occur only in virtue of functionality formed in previous steps [47]. This process repeats until a product stable under the reaction conditions is formed and the reaction terminates. Compared

• with the reductive addition or difunctionalization of the π-system; however, it has been demonstrated the radical intermediate can go through a SET oxidation/elimination to recover the initiating π-functionality. In this review, Fe-catalyzed domino coupling reactions involving π-systems will be

• first three-component alkenylboration of alkenes 50 (Scheme 9) [78]. The authors noted the described methodology regioselectively installs both the boryl functionality and olefin across both activated and unactivated π-systems 50; however, the later required the use of (dppe)FeBr2 in DMF to deliver

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• 4,6-dihydro-3H-pyrazolo[3,4-d][1,2,3]triazines, were not successful under similar conditions due to the higher stability of the triazene functionality in the regioisomeric precursors and thus, the failure of the removal of the protective group. Keywords: cyclization; diazonium chemistry; pyrazoles

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• suitably tailored benzonitriles 3 were cyclized in an intramolecular fashion by installing nuclophilic nitrogen onto the nitrile functionality would generate 1-aminoisoquinolines. Herein we describe our efforts on a Me3Al-mediated nucleophilic addition followed by an intramolecular cyclisation of 2-(2-oxo

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• -1,3-oxathiolane derivative. Further, reduction of the ester functionality with borane dimethyl sulfide at −15 °C afforded the corresponding 2-(hydroxymethyl)-1,3-oxathiolane in 50% yield. It was further treated with benzoyl chloride in the presence of triethylamine (TEA), which provided the desired

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• ][5][6][7]. The reaction involving a nitrogen-based nucleophile as the Michael donor is known as the aza-Michael reaction (aza-MR). In view of its ability to introduce a nitrogen-containing functionality at the β-position of an activated alkenyl- or alkynyl-substrate, over the years, it has developed

• catalytic systems, namely arylboronic acid alone, its dual combination with chiral thiourea and integrated catalyst having boronic acid functionality in the chiral thiourea molecule. The dual combination of arylboronic acid with chiral thiourea was found as effective as arylboronic acid alone for the

• intermolecular asymmetric Michael addition of alk-2-enoic acids 68 with O-benzylhydroxylamine (69) giving racemic mixture of the product in poor yield. However, the integrated catalyst having boronic acid functionality in the chiral thiourea molecule gave the desired β-benzyloxyamino acid as the single product

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• cryogels, degradation of the material is required, yet in many cases the cryogel is still required to perform some functionality during degradation. Therefore, it would be beneficial if the mechanical properties of the cryogel were measured throughout its degradation [25][29]. It has been suggested that

• ) functionality [97]. The cryogels were synthesised by photochemical crosslinking of N,N-dimethylacrylamide (DMA) and β-CD triacrylate (Figure 7) and aripiprazole was incorporated through inclusion inside the hydrophobic β-CD domains. The release of aripiprazole was monitored at pH 1.2 and 6.8, targeting oral

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• comprehensive combination of quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data, to have a unique tetrahydrofuran ring instead of the cyclopropane functionality. The absolute configuration of these five compounds were evaluated and all conserved as C6R, C1’S, C2’R

• the hydrogen source. Following protection of the alcohol moiety with PMBCl, ether 22 was realized in 93% yield. Afterwards, this species was transformed into the γ-keto α,β-unsaturated aldehyde 23 through an NBS-assisted furan oxidation procedure in moderate yield (65%). The keto functionality was

• desired epoxide 30 after one hour in 85% yield (dr 10:1). This species was next converted to the terminal carbonate derivative 31 to transform the epoxy functionality to a vicinal diol through a two-step manipulation involving protection of the terminal alcohol as Boc derivative followed by BF3·Et2O

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• heteroatom (hydroxy, amino) functionality (Scheme 2). Results and Discussion Our studies began (Scheme 3) by reaction of BuLi (4 equiv) with a mixture of stannane 4 [6] (2 equiv) and tetramethylpiperidine (TMP, 2 equiv), to generate methoxymethyllithium and LTMP, followed by addition of terminal epoxide 5

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• respective acid chlorides by using thionyl chlorides and these acid chlorides were then made to react with the -OH functionality of metronidazole to get different esters [7]. Here we report a convenient method for the synthesis of aliphatic and aromatic esters of metronidazole. Furthermore, derivatives of

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• employ the intriguing substrate 5. In comparison with 2-oxindole 4, compound 5 possesses ester functionality directly attached to the 2-oxindole ring – which would provide a functional handle at this position of considerably greater plasticity than anything previously evaluated in the literature. On the

• hydrogen bond-donating functionality – while keeping the N-3,5-di-tert-butylbenzyl unit unchanged – were then introduced. Removing the two electron-withdrawing -CF3 groups from the ureaphenyl moiety resulted in diminished enantioselectivity (Table 1, entry 5), whereas increasing the steric demand in this

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• the previous sections. For example, catalyst 25 bearing a nucleophilic aminoalcohol functionality interacts with the boronic acid reagent in the Reissert-type reaction with acylated quinolines (Scheme 5b) [36], while the phosphine moiety in the bifunctional phosphinothiourea catalyst 31 allows for

• excellent yields and enantioselectivities up to 95% and 98% ee, respectively. Cation–π interaction: expanding the functionality of hydrogen bond donor catalysts: The development of hydrogen bond donor anion-binding catalysts mainly focuses on the interaction and binding properties towards the anionic

• development of an enantioselective aza-Sakurai cyclization (Scheme 12) [70]. In this transformation, a chiral thiourea catalyst 58 with a dibenzothiophene functionality serves as a dual H-bond donor and Lewis base to facilitate the cyclization of hydroxylactams 56. Thus, indolizine and quinolidizine

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• by using [Pd(allyl)Cl]2 and JackiePhos as a ligand to obtain the polymer 30 in 52% yield. The deprotection of the N-Boc functionality led to the formation of poly[2,6-aminoazulene] 31 in excellent yields (Scheme 7C). The N-Boc-protected polymer 30 possessed good solubility in organic solvents and its

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• handles for derivatization and so represent important achievements for this method. In terms of additional functionality, we found that a thioether substrate could be engaged with reasonably good efficiency and enantioselectivity (Table 2, entry 11). On the other hand, while a nitrile was compatible with

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• observed for cellulose [67][79], while the multifluorinated compound formed considerably shorter platelets. Cellulose–xylan [80] and cellulose–chitin [81] hybrids were also obtained upon enzymatic polymerization of the respective dimers. An amino or azido functionality in the C-6 position allows for

• hydroxy group at C-3 and β-selectivity is easily achieved with the help of anchimeric assistance provided by a 2-O-acyl functionality. Despite these advantages, the synthesis of β(1–6)-Glc polysaccharides appears only in few reports [148][149], with short oligomers being prepared mainly to prove new

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• cation chelation via the N-2 atom electron lone pair and the C-3 substituent X=O functionality, respectively [24]. Tight ion pair formation with the sodium cation and both the N-2 atom and C-3 substituents of the indazole scaffold likely hinders the approach of the electrophile to N-2 and directs