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

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• -carbonyl-based Michael acceptors. Results and Discussion Synthesis During our endeavors to identify potent Lewis-base catalysts for the oxa-Michael reaction [13][14], the triarylphosphine 1 was tested in a model reaction (2 equiv allyl alcohol, 1 equiv acrylonitrile, 0.05 equiv 1). However, no conversion

• 3.09 ppm, respectively, and two novel signals for tertiary butyl groups. Accordingly, we reasoned that the phosphine has reacted presumably with acrylonitrile forming a stable species not suited to catalyze the oxa-Michael reaction. In order to identify this compound, we reacted 1 with acrylonitrile or

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

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

• alcohols without a significant change in yield or selectivity. Interestingly, in the absence of the base, the reaction led to fused dioxane derivatives (Scheme 43B). This can be explained by a borylation/oxidation/oxa-Michael tandem sequence instead of the C-Michael addition. The role of the base was

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

• The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut–Currier (RC) dimerization. The other key steps of the synthesis are oxa-Michael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the

• nonetheless, they exhibited very limited growth suppression activity. Keywords: dimerization; incarviditone; incarvilleatone; oxa-Michael; Rauhut–Currier; Introduction (±)-Incarvilleatone (1) is a dimeric cyclohexylethanoid isolated by Zhang and co-workers [1] in racemic form from the Chinese plant

• products (±)-incarvilleatone (1) and (±)-incarviditone (2) could be obtained from the RC product 4 by using oxa-Michael and aldol reactions [3][4]. The RC product 4 in turn can be obtained from a monomeric Michael acceptor, i.e., (±)-rengyolone (3). The Michael acceptor for the intermolecular Rauhut

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

• , United Kingdom 10.3762/bjoc.18.151 Abstract The reactions of aromatic aldehydes and levoglucosenone promoted by methoxide gives bridged α,β-unsaturated ketones, formed by a series of oxa-Michael-initiated cascade reactions in yields of up to 91% (14 examples). A complex series of equilibria operate

• during the reaction, and the formation of the bridged species is thermodynamically favored, except in the case of 5-methylfurfural and pyrrole-2-carboxaldehyde. This is the first report detailing this type of aldol/Michael cascade involving oxa-Michael initiation. Keywords: cascade reactions; green

• chemistry; levoglucosenone; oxa-Michael reaction; Introduction (−)-Levoglucosenone (1) is formed from the acid-catalyzed pyrolysis of cellulose along with minor amounts of furfural and 5-methylfurfural [1][2][3]. It has emerged as a promising starting material for enantioselective synthesis from materials

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• intensities of Hb-3, H-5, and Hab-15, indicating that the carboxyl moiety was α-orientated. Biosynthetically, compound 2 might be derived from compound 4 or compound 5 by oxa-Michael reaction of 7-OH to the α,β-unsaturated carboxylic acid moiety to form a tetrahydrofuran unit followed by ring opening of the

• lactone moiety and demethylation, respectively (Figure 4). Subsequent dehydration would afford compound 2 with an α,β-unsaturated carboxylic acid moiety. Alternatively, the ring opening of compound 4 and demethylation of compound 5 would occur prior to the oxa-Michael reaction. Accordingly, the absolute

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

• to its potential of making a vast variety of organic compounds particularly of pharmacological importance accessible. Over the years, its many versions known as aza-Michael, thio-Michael, oxa-Michael, phospha-Michael, etc. have been developed and well exploited for their synthetic applications [3][4

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

• triphenylphosphine (TPP) in catalyzing oxa-Michael additions. A matrix consisting of three differently strong Michael acceptors and four alcohols of varying acidity was used to assess the activity of the three catalysts. All test reactions were performed with 1 mol % catalyst loading, under solvent-free conditions

• stability of the phosphines was also evaluated and the most electron-rich TMTPP was found to be only slightly more sensitive to oxidation than TPP. Finally, the catalysts were employed in the oxa-Michael polymerization of 2-hydroxyethyl acrylate. With TMTPP polymers characterized by number average molar

• -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

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• products [1][2][3][4][5][6][7][8]. Prins and related cyclization reactions [9][10], hetero-Diels–Alder cyclization [11], cyclization onto epoxides [12], Petasis–Ferrier rearrangement [13], intramolecular oxa-Michael reactions [14], cyclization through oxidative C–H bond functionalization [15], ring-closing

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

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• oxa-Michael additions of 2’-hydroxychalcones [9][10], or through condensation cyclization reactions of o-hydroxyacetophenones with ketones/aldehydes [11][12], in addition to other alternative transformations [13][14]. Moreover, radical cascade cyclizations of o-allyloxybenzaldehydes by employing

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

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

• hydrolysis of the bisdioxines proceeds through the addition of water to a C=C double bond and results in a second transannular oxa-Michael-type reaction and generation of tetraoxaadamantanes 5. This reaction is decarboxylative when free carboxylic acid functions are present in the bisdioxines, thus forming

• 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

• -type double bonds in the bisdioxines under acidic conditions generates a tertiary alcohol, which again undergoes a transannular oxa-Michael-type ring closure forming a tetraoxaadamantane. Free carboxylic acid functions are decarboxylated in this process (Scheme 7), but amide and ester functions are

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

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• intermolecular aza-benzoin reaction is followed by an intramolecular oxa-Michael reaction to form the observed product (Scheme 28). Enders reported a cascade reaction which is initiated by an NHC-catalysed aza-benzoin condensation between various aldehydes and nitrosobenzenes to generate the hydroxamic acids 47

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• enantioselective intramolecular oxa-Michael reaction of an α,β-unsaturated amide mediated by a newly developed benzothiadiazine catalyst. The Weinreb amide moiety and bromo substituent of the Michael adduct were utilized for the C–C bond formations to construct the scaffold. All four contiguous stereocenters of

• the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face. Keywords: bifunctional catalysis; hydrogen bonding; organocatalyst; oxa-Michael; prostacyclin; Introduction Prostacyclin (PGI2, Figure 1) is a physiologically active

• few asymmetric syntheses relying on the optical resolution of racemic intermediates [16][17][18][23]. Herein we report the first catalytic asymmetric synthesis of the key intermediate 2 through organocatalyzed-enantioselective intramolecular oxa-Michael reaction [24][25][26]. Results and Discussion

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

• using them as nucleophilic partners in oxa-Michael additions and the Mitsunobu reaction. The reactions proceed in moderate to excellent yields on a range of substrates containing useful functionality. The reactions serve as practical and valuable synthetic methods to construct complex 2-pyronyl ethers

• , 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

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

• these one-pot enantioselective syntheses. Wherever possible, working mechanistic models are presented. This review work is systematized under the headings (1) Organocatalytic oxa-Michael reactions to access functionalized chromenes; (2) Organocatalytic thio-Michael reactions to access functionalized

• organocatalysts with their percentage of conversion (% yield) and enantiomeric excess (ee) is presented in tabular form, and the best catalyst is used for the given individual scheme. Review 1 Organocatalytic oxa-Michael additions to access functionalized chromenes 1.1. Reactions of 2-hydroxybenzaldehydes with

• acyclic/cyclic α,β-unsaturated compounds The racemic synthesis of 2H-chromene was reported by Bräse et al. in 2005 [39][40]. A strategy based on the organocatalytic enantioselective synthesis of chiral 2H-chromenes through tandem-oxa-Michael–aldol sequence was first reported by Arvidsson et al. [41] in