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

• (RCysNi)L7 formed in the Michael addition reaction was confirmed using the NOESY spectrum. It is illustrated in Figure 1 for (oBrCysNi)L7 complex as the representative example. A correlation between the signal of the H-2 proton at the α-amino acid stereocenter with the signal of the ortho-protons of the

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• outlined in Scheme 4. We proposed that (±)-rengyolone (3) undergoes a hydroxy-directed intermolecular conjugate addition [11][12][13][14][15] with another equivalent of (±)-rengyolone (3) (enone system) to highly selectively afford intermediate A. Via a rapid intramolecular Michael addition of enolate

• to the dihydroxy RC product (±)-4. Synthesis of dihydroxy product (±)-4 was carried out at gram-scale utilizing the key accelerated RC dimerization. In order to synthesize (±)-incarvilleatone (1) first, we needed to perform an oxa-Michael addition reaction. For this, we screened various bases [11][12

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• in a Michael addition with methyl acrylate, affording aldehyde 4 (Scheme 1). Instead of the original Wittig reaction [13], a Horner–Wadsworth–Emmons reaction using diethyl (2-methylallyl)phosphonate and BuLi led to a higher yield and formation of the pure (E)-isomer 5. The required phosphonate was

• , such a synthetic approach would shorten the synthesis from eight to four steps and allow access to both enantiomers of the compounds 12–14. The synthesis started with an enantioselective Michael addition of aldehyde 1 to methyl vinyl ketone (15) catalyzed by (S)-Jørgensen’s organocatalyst S-16, to

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• reaction. This type of olefin E–Z isomerization is likely to take place after the N-acyliminium formation, possibly via a Michael/retro-Michael addition sequence between the chloride (Cl−) anion and the electron-deficient olefin of the N-acyliminium intermediate at 80 °C (Scheme 9c). In conclusion, these

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• significant amount (ca. 75% yield), probably by oxidation of the enol form of 9 [32]. The sensitive aldehyde was thus used without purification to investigate the Robinson-type annulation and a protocol was identified allowing the preparation of cyclohexenone 12 in 40% yield (2-step). Accordingly, the Michael

• addition of ethyl vinyl ketone (EVK), promoted by K2CO3 in a biphasic media (PhMe/H2O), was followed by basic treatment (LiOH) of the keto aldehyde. Since compound 12 bears the desired quaternary carbon of this family of natural products, it was pleasing to reach this milestone, keeping in mind that the

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• decatungstate) [128]. Organic solvent inline nanofiltration is an interesting green approach for solvent recovery that also concentrates, and thus improves the purity of the target compounds. However, this technology is so far only applied in selected examples, such as a Michael addition [129], with continuous

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

• insertion of carbenes derived from diazo arylidene succinimides (DAS) into the O–H bond of phenols is described. The initial adducts underwent a thermally promoted Claisen rearrangement followed by DABCO-catalyzed intramolecular 5-exo-trig oxa-Michael addition. Keywords: Claisen rearrangement; diazo

• arylidene succinimides; intramolecular oxa-Michael addition; rhodium(II) carbene O–H insertion; spirocycles; Introduction Spirocycles undoubtedly occupy a special place in drug design [1] and, in general, spirocyclic compounds intended for the interrogation of biological targets have been associated with

• ) would again have a reactive phenolic hydroxy group which could potentially be involved in post-condensational transformations such as intramolecular oxa-Michael addition (Scheme 1). Herein, we report our findings obtained in the course of investigating the viability of this strategy. Results and

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

• ]. In 2010, Echavarren and co-worker completed the formal total synthesis via a Au(I)-catalyzed cyclization (Scheme 2c) [13]. In 2018, Pabbaraja and co-workers disclosed the synthesis of macarpine by constructing ring C through the domino Michael addition/SNAr reaction of nitromethane to an ynone

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

• , respectively), which are susceptible to basic conditions, were tolerated in the reaction, but ortho substituents hindered the reaction to some extent (Table 2, entries 9 and 10). 2-Hydroxychalcone (3l), which has an electrophilic enone structure, was also tolerated. The Michael addition product was not

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

• the presence of 1.1 equiv of TEA. In this case, the base-promoted deprotonation of 3-bromooxindole (4) affords a highly nucleophilic intermediate, which undergoes Michael addition to FPD 1i, followed by intramolecular SN2 attack [39][40][41][42][43] by the oxygen of the aroyl group (Scheme 5) to give

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

• bridged α,β-unsaturated ketones; however, these reactions do not involve initiation by an oxa-Michael addition [23][24]. The reaction between 1 and aromatic ketones under basic conditions is analogous to the well-known aldol/Michael cascade reaction observed between aldehydes and enolates giving di- and

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

• /mL), a MIC of 128 mg/mL was achieved (Figure 3C). We also investigated whether the reported inhibition of glutathione S-transferase [11] is a result of a Michael addition of glutathione to TDD. However, no reaction occurred between glutathione and TDD in DMF/H2O (1:1) under prolonged stirring at room

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

• , together with the signal of the desired products 6, 10, and 12. The formation of trialkyl propane-1,2,3-carboxylate might be through the Michael addition of the electrogenerated base (E in Scheme 2) to C or the electrochemical reduction of 2. Conclusion A new electrochemical transformation of alkyl 2

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

• base to catalyze the C–C bond formation via a Michael addition of active methylene groups [31]. Therefore, in the presence of TBAB, the bromide assisted with the deprotonation of the phenacylmalononitrile to give a carbanion intermediate A. Secondly, the nucleophilic addition of carbanion A to electron

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• and substituents was also studied during investigation of fluorescence properties of these derivatives. Keywords: β-carboline; DABCO; fluorescence; MBH reaction; Michael addition; structure–fluorescence activity relationship; Introduction Among the polycyclic alkaloids based on indole, the tricyclic

• , it was observed that the MBH reaction of 6b with acrylonitrile A resulted in the formation of product 8bA which evidenced that 6b underwent Morita–Baylis–Hillman reaction at the electrophilic carbonyl center as well as Michael addition reaction at the nucleophilic nitrogen center (N-9). Similar

• . This difference in the fluorescence intensity values of compound 7 and 8 may be attributed to the addition of a substituent at N-9 position of the β-carboline ring after Michael addition reaction (CH2CH2CN or CH2CH2CO2Me). Conclusion In conclusion, we have successfully explored 3-formyl-1-aryl-9H

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

• 1-substituted 2-ethoxy-1,2-azaphospholidine-4-carboxylate 2-oxides 203 were synthesized in 70% and 39% yields, respectively, from ethyl 2-((chloro(ethoxy)phosphoryl)methyl)acrylate (202) and benzyl- and adamantylmethylamines via aza-Michael addition and intramolecular nucleophilic substitution. The

• synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not

• -phenyl-3-phenylamino-2,3,3a,9a-tetrahydro-4H-1,2-azaphospholo[5,4-b]chromen-4-one (215) in 44% yield through the Michael addition and subsequent intramolecular aminolysis (Scheme 34) [15]. The products are potential anti-inflammatory agents. In 2013, to develop potent anti-inflammatory agents, Abdou and

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

• this work. Firstly, the nucleophilic addition of tributylphosphine to the bis-chalcone gives the active zwitterionic species (A). Secondly, the Michael addition of the zwitterionic species (A) to isatylidene malononitrile at the C3-position of the oxindole scaffold results in adduct (B). Thirdly, the

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• enantiopure tetrahedral Pt12 cage has been previously studied for catalytic Michael addition reactions, but no enantioselectivity was detected because the chiral building blocks were located at peripheral positions thus not sufficiently breaking symmetry within the cavity [73]. Therefore, it was envisioned

• defined time). We thus started with the rotor [Cu2(83)(91)]2+ in the presence of ligand 92 as well as organocatalyst N-methylpyrrolidine (89) and the substrates 95 and 96 for a Michael addition (Figure 21). No formation of product 97 was observed, because the complex between the catalyst 89 and the zinc

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

• ) and in the substitution pattern of the macrocycle (R = H or iPr in the 3,5-positions of the phenylene linkers, for 56 or 57; see Figure 14). These heterobifunctional chiral catalysts were studied for the asymmetric Michael addition of malonic acid diethyl ester (59) to cinnamaldehydes 58. While the

• then deprotonated by the amine to generate the enolate nucleophile. After the Michael addition, the anionic intermediate is protonated by the ammonium group to liberate the product. Although this cooperative catalysis is facilitated by the mechanical bond, the racemic background reaction only has a

• the enantioselective Michael addition with different rotaxane catalysts (S)-56a/56b/57a/57b and their non-interlocked counterparts. Synthesis of Beer´s [2]rotaxanes 64a/b for anion recognition. Association constants of different anions (used as the Bu4N+ salts) to the [2]rotaxanes (S)-64a/b and the

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• Michael addition with another molecule of 3-phenacylidieneoxindole to yield intermediate B. Finally, an intramolecular aldol condensation takes place between the carbanion and the carbonyl group of intermediate B towards the formation of the dispirocyclopentanebisoxindole derivative. To support the

• cyclization of two molecules of 3-phenacylideneoxindoles. In this reaction tosylhydrazine serves as reducing agent to reduce one molecule of 3-phenacylideneoxindole to 3-phenacylindolinone which, under base-catalyzed conditions, involves a sequential Michael addition/intramolecular aldol condensation with

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• and efficient organocatalyst. Recent promoted reactions by the resorcin[4]arene capsule include the intramolecular ether cyclization [34], the synthesis of bis(heteroaryl)methanes [35], the imine formation [36], the Michael addition reactions of N-methylpyrrole on methyl vinyl ketone [37], the

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• ketoacids [39]. In the present study, in continuation of our interest in the synthesis of functionalized DHPMs [27], we utilized β,γ-unsaturated ketoesters and subjected them to the melt conditions to achieve the synthesis of 5-unsubstituted DHPMs. We envisaged that the simple Michael addition reaction of

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• phosphonium selenide catalysts which showed catalytic activity in assembly reactions [41], Michael addition reactions [41], Rauhut–Currier reactions [42], cyanosilylation reactions [43], and cycloaddition of vinylindoles through chalcogen–π bonding catalysis [44]. Our previous works demonstrated that Se···O

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

• assigned as 1-alkyl-3,5,5-trimethyl-5,6-dihydro-1H-azepino[4,3,2-cd]indoles 8. The authors proposed that aza-Michael addition of 4-aminoindoles 7 to in situ generated mesityl oxide gives compound 9 which undergoes a regioselective intramolecular cyclization–dehydration sequence to furnish 8. In 2019, Zou

• -cd]indoles 21 from the intramolecular cyclization of Ugi adducts 20 in moderate to good yields and excellent chemo-, regio-, and diastereoselectivity (Scheme 7) [17]. Mechanistically, the reaction involves a tandem gold(I)-catalyzed dearomatization/ipso-cyclization/Michael addition sequence to

• substrates 20. Noteworthy is that substrates bearing an indolyl N–Ph or N–Boc moiety (instead of free indolyl N–H) failed to deliver the corresponding final cyclized products. The authors attributed this failure to the indole C3 position’s reduced nucleophilicity which thwarted the Michael addition step. In

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• ]. Some 4H-3,1-benzothiazines were prepared by intramolecular thia-Michael addition with broad reaction scopes [19]. The rearrangement of 2-isothiocyano triarylmethanes in the presence of AlCl3 were also used for the synthesis 2,4-diaryl-4H-3,1-benzothiazines through aromatic ring transfer [20]. A facile