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

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• cyclopropenimines exemplify Brønsted base organocatalysts that are useful for diverse reactions not easily accessible by other means. Here, Lambert and co-workers employed this type of catalyst in the formation of pyroglutamates via enantioselective Michael addition of amino ester imines [22]. Phase-transfer

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• presence of a multifunctional squaramide catalyst. Michael adducts were obtained in high enantioselectivities and in moderate diastereoselectivities. Keywords: cyclopentane-1,2-dione; enantioselective catalysis; Michael addition; organocatalysis; squaramide; Introduction Diketones are generally very

• substituted cyclopentane diones were uninvestigated until 2014 when we showed that CPD undergoes a Michael addition with nitrostyrenes [22]. Subsequently, different cascade reactions for CPD have been developed: with highly reactive (E)-2-oxobut-3-enoates [23], α,β-unsaturated aldehydes [24] and alkylidene

• malonates [25]. Herein, we report the results of an asymmetric organocatalytic Michael addition of CPD to alkylidene oxindoles. Results and Discussion Chiral multifunctional thioureas [26][27] and squaramides [28] are extensively used as catalysts in asymmetric Michael additions. We believed that a

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• -naphthoquinones 35 and β-lapachone (11) for hCE1 (Scheme 9). It is important to note that 35 can be obtained from other reagents, such as 2-naphthol, in a cascade of reactions involving oxidation to 1,2-naphthoquinones followed by Michael addition to the olefin and reoxidation [85]. In addition, Yang and co

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• through a gram-scale synthesis, one-pot three-component reactions and further transformation experiments of the products. Keywords: asymmetric catalysis; cyclization reaction; Michael addition; one-pot three-component reaction; spirobarbiturates; Introduction Indane scaffolds exist in various

• strategy to construct a series of spirobarbiturates derived from indanone. Combining current researches of these two compounds, we report the first organocatalytic asymmetric Michael addition/cyclization reaction between barbituric acid-derived olefins and indanones (Scheme 1b). Under the action of the

• . Results and Discussion To verify the feasibility of the reaction, the domino Michael addition/cyclization reaction of 2-isothiocyanato-1-indanone (1a) and barbiturate-based olefin 2a was used as a model reaction, which was carried out in dichloromethane (DCM) with 5 mol % quinine-derived squaramide C1 at

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• racemic codonopsinol B (1) and its N-nor-methyl analogue 2 starting from achiral materials. Four consecutive stereocenters in the target molecules were accomplished sequentially by the organocatalytic aza-Michael addition of N-Cbz-protected hydroxylamine to (E)-4-methoxycinnamaldehyde, the trans

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• I-15 leads to enamine I-16. In the presence of the CPA catalyst, an intramolecular Michael addition of the amino group to the enamine in I-16 leads to I-17. Subsequently, the imines I-15 and I-17 are converted to the intermediate I-18, which through elimination by cleavage of the C–C bond gives the

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• aldehydes and hydrogen-bond activation of nitroalkenes. Keywords: asymmetric organocatalysis; hydrogen bond; Michael addition; pyrrolidine; thiourea; urea; Introduction Asymmetric organocatalysis became one of the strategic ways for the efficient synthesis of chiral compounds [1]. Bifunctional catalysis

• Michael addition of thioacetic acid to aromatic and aliphatic nitroalkenes to produce chiral β-aminothiols, compounds of pharmaceutical interest [26]. Similarly, the enantioselective addition of thioacids to trisubstituted nitroalkenes was catalyzed by several N-sulfinylureas providing the 1,2

• )-C1 as well as N-sulfinylureas (S,R)- and (S,S)-C2 in excellent yields (Scheme 2). Application of thioureas C1 and ureas C2 in the Michael addition of aldehydes to nitroalkenes Michael addition in solution As the first benchmark transformation, we opted for the Michael addition of butanal (6a) to β

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

• aromatic amines, amides, imides, etc. require the use of an appropriate catalyst to undergo a Michael addition with a suitable acceptor. In view of this, chemists endeavoured to develop different types of catalysts, particularly the chiral catalysts to accomplish asymmetric aza-MRs. The development of

• subsequently deprotonates pyrrole to provide the stronger nucleophilic pyrrolide anion [27]. Similarly, Liu et al. accomplished an asymmetric intramolecular aza-Michael addition of various enone carbamates 10 using a chiral cinchona-based primary-tertiary diamine as catalyst to obtain 2-substituted piperidines

• appears that in this case, both activation mechanisms, namely through hydrogen bonding and iminium ion formation are operating. Using the same chiral cinchona-based primary-tertiary diamine as catalyst (cat. 11), Zhai et al. developed a highly efficient intramolecular enantioselective aza-Michael addition

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• yield. Aliphatic amines were also tolerated, providing the desired products in only moderate yield. The plausible mechanism involves a tandem base-promoted aza-Michael addition, 1,2-iodocyclization, and iodine-mediated oxidative aromatization. In 2017, Zhang and co-workers reported a silver-catalyzed

• standard conditions. The proposed catalytic cycle included aza-Michael addition of arylamines, Lewis acid copper(II)-catalyzed intramolecular 5-endo-dig cyclization, protonation, and oxidation to provide the final products, tetrasubstituted pyrroles 39. The introduction of a trifluoromethyl group into

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• ], rhodium-mediated alkyne [2 + 2 + 2] cycloaddition reactions [3], and the palladium-catalysed aerobic domino Suzuki coupling/Michael addition reaction [4]. The most attractive and common strategies to phenanthridines rely on intramolecular cyclizations of various ortho-functionalized biaryl precursors