Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• elimination to form an alkene or intermolecular nucleophilic attack by formic acid (ultimately giving a formate ester) are reasonable mechanistically, only the intramolecular nucleophilic attack by the carbonyl group of the pendent ethyl ester was observed in this system to form the resonance-stabilized

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• developed the total synthesis of macarpine by Hofmann elimination from protoberberine by introducing rings B and C (Scheme 2a) [11]. In 1995, Ishikawa and co-workers accomplished the total synthesis via a Reformatsky reaction and aromatic nitrosation through the building of rings B and C (Scheme 2b) [12

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• –elimination pathway (SNHAE), where deoxygenation of imidazole 1-oxide resulted in the formation of perfluoroarylated 2H-imidazoles; and (B) addition–oxidation pathway (SNHAO), where without affecting the N–O bond of imidazole 1-oxides, perfluoroarylated 2H-imidazole 1-oxides were obtained as final products

• vicinal position of 2H-imidazole and the addition–elimination pathway providing the products 10a–h or addition–oxidation pathway affording the corresponding products 11a–h (Scheme 2). At first, pentafluorophenyllithium (13) which was produced through the reaction between n-BuLi and pentafluorobenzene (12

• ), acted as the nucleophile to attack the C-5 position of 2H-imidazole 1-oxides 9a–h to form the σH-adduct 14. The use of a deoxygenation agent in the mixture led to the formation of the desired products 10a–h via “addition–elimination” (SNH AE, path A) from the adduct 14 with the elimination of the good

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• difluoroalkyl ethers (1), along with small amounts of fluoroalkenyl ethers (2), which were obtained from 1 via an E2-elimination mechanism (Scheme 1B) [14][15]. The fluoroalkenyl group in 2 is a potentially useful moiety that could participate in cross-coupling reactions for replacement of the bromine atom with

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• negatively charged [38] C(3) atom of diazooxindoles 2 at the C(3a) atom of FPDs 1 (Scheme 5), and (b) further intramolecular SN2 attack by the oxygen of the aroyl group with ensuing elimination of a nitrogen molecule. To verify our assumption, 3-bromooxindole (4) was involved in the reaction with FPD 1i in

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• proposed (Figure 5). Firstly, by the interaction of TC-6 with 1a/2a under the “dehydrogenative” process, the Int-I/Int-II were formed [28][29]. Then, Int-III and 2-aminobenzaldehyde (5)/acetophenone (6) were formed by β-H elimination of Int-I/Int-II. In this process, an amount of liberated H2 would be

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• . With the elimination of hydrochloric acid, intermediate A is converted to intermediate B. When a base such as Et3N was added, hydrochloric acid was trapped and lowered the reaction yield (Table 1, entry 18). The nucleophilic attack of chloride ions on intermediate B produces D via C, which entails

• isomerization with the elimination of the sulfur-and-bismuth moiety. Aminophenol then reacts with D to generate intermediate F via E, which is converted to the benzoxazole 8, accompanied by the elimination of 19 by aromatization. The generation of hydrochloric acid was important in this reaction, and the

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• elimination of methanol rather than exocyclic elimination of water, and regioisomeric Rauhut–Currier reaction. Compound 7 was found to be unstable after isolation, possibly due to intermolecular reactions of the electron-poor olefin and furan ring. When a slight excess of 1 was used, only 6n was isolated

• presumed to start with an oxa-Michael initiated aldol reaction promoted by a methoxide nucleophile giving enone 6 via enolate 8 (Scheme 1). A Rauhut–Currier-type reaction of 6 with the addition of another equivalent of 8, followed by a subsequent double β-elimination leads to the observed product 5. When

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• ) function as sterol 14α-demethylases in green plants [24][25][98]. These enzymes catalyse oxidation of the C14α methyl group to trigger elimination of formic acid [24][25]. The sister subfamily CYP51H, on the other hand, is only found in monocots. AsCYP51H10 from Avena sativa (oat) is a multifunctional CYP

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• for the reaction between N6-substituted adenine anions 1–5 and FcCOCl. In no case the tetrahedral intermediate, typical of a nucleophilic addition–elimination pathway, was located as a genuine minimum on the potential energy landscape. Instead, the structure with tetrahedral geometry corresponds to

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• alcohol 6 with amberlyst-15® leading to the monoterpene 1. Other systems tested for the elimination of the hydroxy group in 6 were pyridinium p-toluenesulfonate (PPTS) and camphorsulfonic acid (CSA), that gave poorer results, failing to afford a single product. On the other hand, lactone 5 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

• , Scheme 6) [15]. Through a series of finely tuned CH oxidations, cedrol (31) was converted to the lactone 32. In a single step, using Riley oxidation conditions, the methyl ketone moiety was transferred to the α-ketoester 33. Reduction, lactonization, and elimination gave the ketoesters-derived enol 34

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• -electrocyclization of the initially formed pyridinium alkoxycarbonyl-dichlorophosphinomethylide followed by 1,2-elimination affording 1,3-bis(alkoxycarbonyl)-2-phosphaindolizines [5]. After having access to a good number of differently substituted derivatives of these four classes of 2-phosphaindolizines, we were

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• DBU is a common strategy for the dehydration of serine and threonine units in peptides [16], but unfortunately the acetylation of 10 failed. Interestingly, the direct treatment of 10 with LiClO4 and DBU under prolonged reaction times (3 days) resulted in the elimination of water. This reaction

• basic treatment with DBU in the last step. This was confirmed by HPLC analysis on a chiral stationary phase, showing that the obtained target compound 4 was nearly racemic (Figure 1A). Because of the configurational instability of 4 under base treatment, we aimed at an approach for the final elimination

• 13. Removal of the Cbz group by catalytic hydrogenation proceeded with spontaneous cyclisation to 14. With this material, the elimination of the MOM group smoothly proceeded by treatment with KH and 18-crown-6 in THF at 25 °C to 15, that upon removal of the Boc group with TFA and 1,3-dimethoxybenzene

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

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

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• the exclusive isolable product when benzene was eliminated from the reaction mixture (Table 1, entry 6). Interestingly, the formation of byproduct 15 (which could be, in principle, obtained by DDQ oxidation of 11 [25]) via the elimination of a diazo group has not been reported. Having identified the

• ). Mechanistically, the arylation of diazo substrates 10 likely proceeds via the protonation of the diazo moiety and elimination of a nitrogen molecule, whereby carbocation 17 is generated. The latter can either be deprotonated to give byproduct 15 or be intercepted by an arene molecule in SEAr fashion to give

• available 3(2H)-isoquinolones followed by TfOH-promoted arylation. The generally high-yielding two-step sequence was shown to be applicable to a wide range of substrates. To a varying degree, the arylation step was accompanied by the elimination of the nitrogen molecule and deprotonation to furnish 3

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• reaction of phenacyl bromide, malononitrile, dialkyl but-2-ynedioate, and triphenylphosphine has been already reported, in which diethyl 3-phenyl-5,5-dicyanocyclopent-2-ene-1,2-dicarboxylates were produced by further elimination of a hydroxy group [30]. In the present reaction, the hydroxy group is still

• be seen that the C–C double bond is connected to two methoxycarbonyl groups. Though one hydroxy group exists on the reactive allyl position and benzyl position, it still is present in the molecule and did not give the cyclopentadiene by further elimination of water. In order to obtain the

• corresponding products with elimination of water, alternative conditions for the base-promoted reaction of phenacylmalononitrile and dialkyl but-2-ynedioates were tested. After carefully examining the reaction conditions, we found that the reaction of phenacylmalononitriles and dialkyl but-2-ynedioates in

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

• )(phenyl)phosphinate (53) was reduced with lithium aluminum hydride to 2-aminobenzyl(phenyl)phosphine (57). It was oxidized with sulfur to give zwitterionic 2-aminobenzyl(phenyl)dithiophosphinic acid (58), which underwent thermal elimination of hydrogen sulfide to yield 2-phenyl-1,3-dihydrobenzo[d][1,2

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• seems to undergo elimination of difluorocarbene to generate a phenylthiolate anion which reacts with compound 1 to form product 3 as shown in Scheme 6. In order to confirm the proposed reaction pathway to product 3, the reaction of bromodifluoromethyl phenyl sulfide (1) with phenylthiolate anion was

• reaction mechanism as shown in Scheme 11. The one-electron reduction of 1 generates the PhSCF2 radical A, which abstracts a hydrogen radical from MeCN to give product 2 (path b). The radical A undergoes further reduction to generate anion B (path a). Elimination of difluorocarbene from anion B forms a

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• intermediate A to form a π-complex B, and a ligand exchange reaction from B occurs to produce intermediate D, together with the elimination of selenol C. The selenol C is oxidized to diselenide 2. Finally, the intermediate D undergoes a reductive elimination to form the desired product 4, with the regeneration

• phenyllithium in THF at −78 °C led to a nucleophilic substitution reaction with the elimination of the ethynyl group to form the desired phenylimidazopyridinyl selenide 6a in 49% yield. In the reaction with n-butyllithium, alkyl derivative 6b was isolated in the same way. The reaction of 4aa with the Ruppert

• synthesized using a simple operation that can be performed under aerobic conditions. Moreover, the results showed that the obtained compounds underwent nucleophilic substitution reactions involving the elimination of the alkyne moiety on Se atoms to form aryl or alkyl imidazopyridinyl selenides and

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• of aromatics, for which trifluoromethylation was also possible in good to high yields for electron-rich aromatic rings [10]. In this protocol, inspired by Norrish type I reactions and the elimination of β-substituents after ketone photoexcitation [11][12][13], a series of reagents containing an α

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• conditions (temperature) and the inability to control the elimination process [17]. The objective of this work was to establish whether the 1,2-debromination with the Zn/Ag couple could be carried out under solvent-free conditions in a ball mill and whether the tedious Zn/Ag couple preparation procedure [18

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• antidepressant hydrochloride of amitriptyline (84) was the target of a multistep continuous flow protocol in which, for one reaction step, inductive heating was used to achieve water elimination triggered exclusively under thermal conditions [54]. The flow process started with a multilithiation sequence which

• included a carboxylation and a Parham cyclization and hence a Grignard alkylation of ketone 82 using reagent 81. The resulting alcohol 83 was subjected to thermolysis that led to water elimination. This step proceeded in just 30 s by employing the inductive heating technique. The crude elimination product

• multistep flow synthesis of Iloperidone (80) accompanied with a “catch and release” purification protocol. Continuous two-step flow process consisting of Grignard reaction followed by water elimination being the last steps of a multistep flow synthesis of the hydrochloride salt of amitryptiline 84

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• four mechanistic pathways could be involved in this reaction [51]. Three of them involve oxidative addition followed by reductive elimination. Neutral NBS or the hydrogen bond complex NBS∙∙∙TsOH are bromine donors in two of them, while protonated NBS is engaged in the third. The fourth mechanism

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• intramolecular addition of the carbanion to the enone affords the cyclic intermediate (C), which in turn converts into the intermediate (D) by transfer of a negative charge. Finally, the spiro compound 3 is formed by elimination of tributylphosphine. When 3-(ethoxycarbonylmethylene)oxindole 4 is employed in the

• alkoxide to the carbonyl group in the ester moiety produces the cyclic intermediate (J). Finally, the dispiro compound 8 is formed by elimination of tri(n-butyl)phosphine oxide. Conclusion In summary, we have investigated tri(n-butyl)phosphine-catalyzed annulation reactions of bis-chalcones with

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• attack of the amino group of 2-aminopyridine to maleimide 1, followed by elimination of the methylsulfanyl group, and subsequent cyclization (Figure 1). The ring-fused pyridine compound 3b was obtained from the reaction of 1 with 2-aminopyridine 2b, which has an electron-donating methyl group at position