Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• undergoing yet another diastereoselective 6-endo-trig intramolecular oxa-Michael addition. The structure and stereochemistry of compounds 3 and 4 were confirmed by 1H-1H-COSY and 1H-1H-NOESY NMR experiments. This was further unambiguously established by single crystal X-ray analysis of a representative

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• synthesis of spiro-annulated pyrrolidine-2,5-diones by catalyzed spirocyclizations involving aldehydes [11], tetrahydrofuran [12][13], and in the O–H insertion/Claisen rearrangement/intramolecular oxa-Michael addition cascade [14] (Scheme 1). Herein, we report our findings obtained, while investigating 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

• 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

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

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

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• dihydrocinchonine 26 in combination with trifluoracetic acid (TFA) as Brønsted acid [39]. The reaction provides pyranocoumarins 25 with three vicinal stereogenic centers in high regio-, diastereo- and enantioselectivities through a tandem allylic alkylation/intramolecular oxa-Michael addition (Scheme 7). A

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• -Michael addition. Triphenylphosphine (TPP), (4-methoxyphenyl)diphenylphosphine (MMTPP) and tris(4-trimethoxyphenyl)phosphine (TMTPP). The catalysts were investigated in the reaction of four different Michael acceptors with four different alcohols. In the oxa-Michael addition, the zwitterion i, initially

• generating the ion pair iii. In the final step, the α-carbanionic species in iii gets protonated by an alcohol generating the oxa-Michael addition product (iv) and regenerating ii (Scheme 1). Additionally, the ion par ii might directly react via a nucleophilic substitution of the phosphonium group by the

• slightly lower than the activity of the methoxy-substituted congeners. As an example for acrylates as Michael acceptors, the performance of the catalysts in the oxa-Michael addition polymerization of 2-hydroxyethyl acrylate (HEA, 4) was investigated [27][28][29]. The catalyst loading was increased to 5 mol

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• catalysts, this group found that the intramolecular oxa-Michael addition using 20 mol % of the diarylprolinol organocatalyst 37 in the presence of benzoic acid gave 38. The use of the enantiomer of 37 gave the dihydropyran with the opposite configuration at C-11. The catalytic hydrogenation of 38 proceeded

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• reaction (Scheme 7), and not in the final products, which are not prone to decarboxylation: the stable bis-carboxylic acid 24 can be obtained by hydrogenolysis of the dibenzyl ester 23 (Scheme 6) [30]. The reaction may be seen as a decarboxylative [31][32] oxa-Michael addition (Scheme 7) and may be related

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• precursor and thus particular ring systems [9][10][11]. Most heterocycles in polyketides are formed by specialised PKS domains and tailoring enzymes. These can be active during assembly of the nascent PKS precursor (as for example in the case of pyran/furan formation via oxa-Michael addition, see chapters

• (f in Scheme 2). The oxidative cyclisation after C–H activation of alkyl carbons is known for the formation of furan rings 21 (g in Scheme 2). 1.1 Pyrans 1.1.1 oxa-Michael addition: The oxa-Michael addition on an α,β-unsaturated thioester intermediate leads to oxygen heterocycles along with the

• proposed mechanism also proceeds via a dehydration–oxa-Michael addition cascade. A crystal structure revealed two crucial aspartic acid residues as candidates for the acid–base catalysis occurring in the active site [18]. 1.1.2 Processing of hemiacetals: Reduction or alkylation of hemiacetals in the

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• aldehyde fragment 6 by asymmetric alkynylation, and form the pyran using an oxa-Michael addition, in a manner reminiscent of that employed by Uenishi and co-workers [34]. Finally, macrocyclisation will be achieved through the well-established strategy of ring-closing metathesis at C8–C9. Results and

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• hydroperoxides with pendant alkenes or alkynes have been developed. Selected examples include Pd(II)-catalyzed hydroalkoxylation reactions of unsaturated hydroperoxides [9], Au(I)-catalyzed endoperoxidation of alkynes [10] and Brønsted acid-catalyzed enantioselective acetalization/oxa-Michael addition cascade

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• , which are found embedded in a number of natural products. Keywords: heterocycles; Mitsunobu reaction; oxa-Michael addition; 2-pyrone; vinyl ethers; Introduction The 2-pyrone motif is a prevalent structural feature of many complex natural products and biologically active compounds [1][2]. Various

• part of our extensive studies on reactions involving 2-pyrone derivatives, we report herein a significant expansion of the Mitsunobu protocol to a variety of different coupling partners, along with an alternative route to the formation of 2-pyronyl enol ethers using an oxa-Michael addition to

• procedure 2: Oxa-Michael addition with 4-hydroxy-2-pyrones: The pyrone (1 equiv), triethylamine (1 equiv) and propiolate ester (2 equiv) were stirred in CH2Cl2 (2 mL mmol−1) at 45 °C for 16 h. The solvent was then removed in vacuo and the product purified via flash column chromatography to afford the

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• neuraminidase (NA) inhibitor, was synthesized by using a bioinspired, organocatalytic enantioselective 1,4-conjugate addition of styryl-2-pyranone with cinnamaldehyde, followed by a tandem Horner–Wadsworth–Emmons/oxa Michael addition. Keywords: bioinspired synthesis; catalysis; katsumadain A; natural product

• the way for their application in further biomedical investigations. Biosynthetically, katsumadain A is assumed to be derived from styryl-2-pyranone 3 and alnustone (4) [9] through a 1,6-conjugate addition/oxa-Michael addition cascade reaction (path a, Scheme 1). Indeed, both 3 and 4 are known natural

• strategy was designed as a fallback, in which katsumadain A could be accessed from the lactol 5a and phosphonate 6 via a tandem Horner–Wadsworth–Emmons (HWE)/oxa-Michael addition reaction [16]. In turn, 5a could be derived from 3 and cinnamaldehyde (7) by an organocatalytic enantioselective 1,4-conjugate

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• observation of a trace of intermediate, only one enantiomer was observed in this reaction, probably due to the first oxa-Michael addition, which is known to proceed with high diastereo- and enantioselectivity, and the resulting product presumably directs the stereochemistry of the subsequent reactions. This

• -Michael addition followed by aza-Baylis–Hillman reaction by means of an iminium-allenamine activation strategy. Later on, the same authors [49] in 2011 reported a similar tandem reaction (abnormal Baylis–Hillman) between 2-alkynals 5 and salicylaldehyde derivatives 1 catalyzed by proline derivatives

• 7 (Michael donor) with 2-alkynals 5 using diarylprolinolether Ia as organocatalyst (Scheme 7). The reactions were carried out in toluene at room temperature and completed within 2 h, giving high yield (>97%) and excellent enantioselectivity (99%). Mechanistically the reaction proceeded through oxa