Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• reaction between 2-amino-5-chloropyridine (1a), 2-(3-formylphenoxy)acetic acid (2) and tert-butyl isocyanide (3a) was chosen for the first step (Scheme 3). In one of the previous works [34], our group has shown that the optimal conditions for this type of reactions are stirring the starting materials for

• heterocyclic acid 8a was obtained by a three-component reaction of 2-amino-5-chloropyridine (1a), 4-formylbenzoic acid (5f), and tert-butyl isocyanide (3a) according to the procedure described above (Scheme 3). In another step, we attempted to introduce the acid 8a into the Ugi four-component reaction with 4

• -chlorobenzaldehyde (5b), 4-methoxyaniline (6a) and tert-butyl isocyanide (3a). It should be especially noted that the solubility of compound 8a is very low (soluble in DMSO and N-methyl-2-pyrrolidone (NMP), slightly soluble in methanol, 1- and 2-propanol, acetone, DMF and insoluble in water, ethanol, acetonitrile

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

• synthesis of 1,2-oxaphosphaheterocycle 2-oxides. tert-Butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoate (11) generated tert-butyl 2-(allyloxy)-3,4,7-trihydro-1,2-oxaphosphepine-3-carboxylate 2-oxide (12) in excellent 94% yield in the presence of the Grubbs catalyst in DCM. After further allylation with allyl

• bromide, its allylated product 13 further cyclized into bis(1,2-oxaphosphepine 2-oxide) derivative tert-butyl 2,5,5a,6,9-pentahydro-[1,2]oxaphosphepino[2,3-b][1,2]oxaphosphepine-5a-carboxylate 11-oxide (14) in 97% yield under the same conditions (Scheme 2) [27]. The Grubbs 1st generation catalyst-promoted

• from tert-butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoate. Synthesis of 2-ethoxy-5H-benzo[f][1,2]oxaphosphepine 2-oxides from 2-allylphenyl ethyl vinylphosphonates. Synthesis of 2-ethoxy-3,6-dihydrobenzo[g][1,2]oxaphosphocine 2-oxides from 2-allylphenyl ethyl allylphosphonates. Synthesis of

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• , benzylamine, and arylamines 11, while alkylamines are unsuitable for it. Notable, the use of bulky nucleophiles (tert-butyl alcohol (16a), benzyl alcohol (16b), benzhydrol (16c), 2-aminobenzothiazole (16d), HCl) makes it possible to obtain pyrrolobenzothiazoles 17 from compounds 1, but their formation

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

• synthesis of enantiomerically enriched cyclobutanes 77 [52]. Their strategy employed a three-component process in which tert-butyl (E)-2-diazo-5-arylpent-4-enoates 74 were treated with the chiral rhodium catalyst C1 to provide enantiomerically enriched bicyclobutanes 75. These highly strained compounds then

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

• )-1-benzylpyrrolidine-2-carboxamide) and its Ni(II)–Schiff base complexes formed of glycine, serine, and dehydroalanine are reported. A bulky tert-butyl substituent in the phenylene fragment precludes unwanted oxidative dimerization of the Schiff base complex, making it suitable for targeted

• electrochemically induced oxidative modification of the amino acid side chain. Experimental and DFT studies showed that the additional tert-butyl group increases the dispersion interactions in the Ni coordination environment making the complexes more conformationally rigid and provides a higher level of

• thermodynamically controlled stereoselectivity as compared to the parent Belokon complex. Additionally, functionalization with the tert-butyl group significantly enhances the reactivity of the deprotonated glycine complex towards electrophiles as compared to the anionic species formed from the original Belokon

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

• (5). This compound was synthesized smoothly within three steps in 16.6% overall yield. The synthetic route commenced from the preparation of N-protected amine 3, followed by the deprotection of benzylamine 3 to furnish 4 and ended with the diazotization of 4 using tert-butyl nitrite. As a result, the

• 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

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

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• -difluoroethanesulfinate (DFES) and zinc difluoromethanesulfinate (DFMS). In brief, a mixture of the respective scaffold, Diversinate™ (2 equiv), and TFA (5 equiv) in DMSO/CH2Cl2/H2O (5:5:2) was stirred for 30 min at room temperature and cooled to 4 °C. Then, aqueous tert-butyl hydroperoxide (TBHP, 70%, 3 equiv) was

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• similar efficiency, affording oxindole 3aj as a 1:1.1 mixture of diastereomers. Interestingly, this method also enabled the synthesis of the highly sterically demanding oxindole 3ak in good yield when using a tert-butyl N-hydroxyphthalimide ester as the tert-butyl radical precursor. Importantly, a redox

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

• Discussion The initial attempt to involve DAS 1b in the Rh2(esp)2-catalyzed insertion reaction with 4-(tert-butyl)phenol was successful. The initial adduct 5b was not purified and was heated at 140 °C in toluene to give compound 6b in 47% yield over two steps (Scheme 2). No further optimization of the

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

• . Mechanistic investigation of the intramolecular cyclization The reaction mechanism of the intramolecular cyclization can only be speculative at this stage. We have already reported the generation of a rhodium hydride (Rh–H) complex from RhCl(PPh3)3 and Et2Zn, in which the reaction with tert-butyl acrylate

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• methanol (20 mL), then 5% hydrochloric acid (5 mL) was added and stirred for 2 hours at 50 °C. After complete deprotection (TLC reaction control!), the solvent and all volatiles were removed under reduced pressure and the crude residue was suspended in dichloromethane (6.5 mL). Afterwards, di-tert-butyl

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• determined using the modified Mosher’s method [21]. Protection of diol 25 by tert-butyl(dimethyl)silyl (TBS) group followed by selective deprotection of the primary alcohol led to 27. Finally, acid 7 was obtained from alcohol 27 through the same two-step oxidation used to obtain compound 10. Having

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• stabilization of the complex through weak hydrophobic interactions of with tert-butyl groups of Boc. We believe that by adjustment of the substituents on the amide/carbamate groups, receptors for supramolecular sensing of alcohols [44] could be designed based on 3N-TAADs of type 4. Further research in this

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• ethylenediamine monohydrochlorides were grinded with a half equivalent of 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (blue moieties in Scheme 2) for 10 minutes. The synthesis of diamine monohydrochlorides and characterization data of mono-imine ammonium salts were

• ), half equivalent of 5-bromo (Br‒), 5-methyl, 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (red moieties in Scheme 2), and trace methanol, followed by grinding for 20 minutes for the second reaction step to complete, monitored by TLC. A trace amount of

• between 1g (81%) and 1h (76%). Yields of 1d (79%), 1e (81%), and 1f (72%) were less than 1a‒c, caused by the steric hindrance of di-tert-butyl groups. In the aspect of characterization of salens, two singlets were shown at around 8 ppm in the 1H NMR spectrum, indicating two unsymmetrical imines. The broad

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• /z): [M + H]+ calcd 407.2377; found, 407.2359. (6R)-tert-Butyl 5-(diethoxyphosphoryloxy)-6-(2-((triisopropylsilyl)oxy)ethyl)-3,6-dihydro-2H-1,2-oxazine-2-carboxylate (10b): A solution of the enol phosphate 17 (420 mg, 1.03 mmol) in chloroform (1.8 mL) was added to a solution of the Wightman reagent 6

• ppm; HRMS (m/z): [M + Na]+ calcd 560.2779; found, 560.2775; [α]20D : +5.8 (c 1.0, CH2Cl2); ee: 8% (Whelk-O1, 1 mL/min, 95:5 hexane/EtOH, tr (R) = 14.9 min, tr (S) = 16.2 min). (6R)-tert-Butyl 5-oxo-6-(2-((triisopropylsilyl)oxy)ethyl)-1,2-oxazinane-2-carboxylate (11b): A solution of the cycloadduct 10b

• %). tert-Butyl (6R)-5-((E)-2-((2S,3S)-3-ethyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)vinyl)-5-hydroxy-6-(2-((triisopropylsilyl)oxy)ethyl)-1,2-oxazinane-2-carboxylate (25): Data for 25: Rf: 0.10 (30% AcOEt/cyclohexane); 1H NMR (360 MHz, CDCl3) δ 6.97 (dd, J = 9.7, 5.5 Hz, 1H), 6.05 (d, J = 9.7 Hz, 1H), 5.95 (dd, J

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

•  1b). Alternatively, the oxidation of α-C–H of active methylene ketones generate α-carbon-centered radicals, thus providing another way to obtain thiazoles. Recently, Sun et al. reported a tert-butyl hydroperoxide/azodiisobutyronitrile-mediated synthesis of 2-aminothiazoles from active methylene

• presence of ᴅʟ-alanine (Table 1, entry 24). Under the optimized reaction conditions (entry 24, Table 1), the scope of the electrochemical reaction was studied using a series of active methylene ketones (Scheme 2). Various linear and branched alkyl acetoacetates including methyl, ethyl, tert-butyl, and amyl

• ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and cyclohexyl moieties were also compatible with the optimized conditions, providing the corresponding 2-aminothiazoles in 24% to 65% yields (3g–l). As shown in Scheme 2, when the R1 group changed from alkyl to aryl, the target products could also be

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

• thermodynamically controlled basic intramolecular aldol addition of compound 108 using the bulky amine base 2,6-di-tert-butyl-4-methylpyridine (DTBMP) led to epimerization of the methyl group and cyclization, giving preussochromone F (109) as single isolable diastereomer probably via transition state XII. The

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• ). N-(1-Naphthyl)formamide (6) was obtained in satisfying yield, while the methyl and tert-butyl ester moieties affected the reaction outcome (Scheme 1, amides 7 and 8). Secondary amines were also tested under the developed conditions; N-methylaniline provided the desired product 9 in 39% yield, while

Thermally activated delayed fluorescence (TADF) emitters: sensing and boosting spin-flipping by aggregation

• Ashish Kumar Mazumdar,
• Gyana Prakash Nanda,
• Nisha Yadav,
• Upasana Deori,
• Upasha Acharyya,
• Bahadur Sk and
• Pachaiyappan Rajamalli

Beilstein J. Org. Chem. 2022, 18, 1177–1187, doi:10.3762/bjoc.18.122

• to the singlet state via RISC [17][27]. Heteroatom lone-pair electrons are sensitive to acid and, once protonated, to base, which would facilitate the tuning of optical properties in such media [21][22]. Herein, (4-(3,6-di-tert-butyl-9H-carbazol-9-yl)phenyl)(pyridin-4-yl)methanone (BPy-pTC) and (4-(9

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• compound 6 in <24% and <26% yields, respectively (Table 3, entries 3 and 4). n-Propyl 2-chloroacetate (9), with the longer alkyl chain, and tert-butyl 2-chloroacetate (11), with the bulky alkyl group, produced 10 and 12 in <22% and <31% yields, respectively (Table 3, entries 5 and 6). The reaction of 13

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• transformation was investigated as shown in Scheme 2. Various 1-arylethanol derivatives were firstly examined. Substrates bearing p-methyl (1b) or p-tert-butyl (1c) groups afforded the desired products 2b and 2c in moderate yields. Halogen substituents such as fluorine (1d) and chlorine (1e) atoms were tolerated

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• performed a detailed investigation on the dearomatizing anionic cyclization of diphenyl-N-alkyl-N-benzylphosphinamides 107, 116, and 119 by treatment with sec-butyllithium and protonation with various alcohols (MeOH, iPrOH, t-BuOH), phenols (PhOH, 2-tert-butyl-4-methylphenol, and 2,6-di(tert-butyl)-4

• -dihydrobenzo[c][1,2]azaphosphole 1-oxide (210) was synthesized in low yields of 20–43% with diastereomeric ratios of 10:1 to >20:1 from (R)-1-tert-butyl-1,1-diphenyl-N-(1-phenylethyl)silanamine (204) via the treatment with butyllithium followed by double displacement with four different phosphorus

• )acetates 247 in moderate yields of 53–71% with diastereomeric ratios of 1:1.7 to 1:3. The synthetic strategy is more versatile (Scheme 39) [60]. [3 + 2] Annulation via formations of both C–C and P–N bonds After oxidation with K3Fe(CN)6, diphenyl 3,5-di(tert-butyl)-4-hydroxybenzylphosphonate (248) was

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• ], tert-butyl/α,α-gem-dimethyl [29], or fluorinated groups [30] will preferentially form cis-amides (Figure 1A). Peptoid helicity modulation has also been investigated through specific placement of chiral and achiral monomers [31][32]. Comparatively fewer N-functional monomers capable of promoting trans

• -methylhydrazine as a submonomer was adopted in this work (Figure 2). Benzyl bromoacetate, rather than tert-butyl bromoacetate, successfully used in the past for the synthesis of peptoids in solution [22], was chosen as the starting substrate to ensure orthogonality of the C-terminal protecting group with respect

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• be extracted from grapefruits or prepared by, e.g., oxidation of (+)-valencene (7) (using toxic di-tert-butyl chromates), which is isolated from the essential oil of oranges [9]. In 2014, Neuenschwander and Jensen reported a flow setup for the catalyst and solvent-free oxidation of (+)-valencene (7