Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• (Scheme 3a). Based on the well accepted metathesis reaction of Cu(I) alkoxides with B2pin2 and the reactivity of the resulting Cu–Bpin complex towards α,β-unsaturated esters and hydrocarbons [8][9][10][11][12][13][14][15], we hypothesized that the first step of the reaction may deal with the insertion of

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• that α,β-unsaturated esters could potentially also undergo energy transfer in the presence of high energy sensitizers [59][60], the system 4e with two ester components was also designed. The reaction proceeded cleanly to the cycloadduct, indicating sensitization of the acrylate is also operational

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• lengths and angles fall within the expected range for similar compounds [31]. Later, the β-sulfinyl esters 4 were prepared by Michael addition reaction of thiols and α,β-unsaturated esters [32], followed by oxidation of the corresponding sulfides 3 using two different oxidizing agents (oxone and m-CPBA

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• leads to the formation of the target product 139. Later, iron-catalyzed three-component reactions of α,β-unsaturated carbonyl compounds 140, aldehydes 141, and TBHP leading to α-ester-β-keto peroxides 142 have been developed (Scheme 45b) [106][107][108]. Radical coupling of arylaldehydes 144 with α,β

• -unsaturated esters 143 and TBHP to afford α-peroxy-γ-diketones 145 was also disclosed under the catalysis of dirhodium(II) complex Rh2(esp)2 (esp = α,α,α′,α′-tetramethyl-1,3-benzenedipropanoate) (Scheme 45c) [109]. A three-component radical coupling reaction has been established for the assembly of β

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• mainly afford 2-substituted 3-hydroxyesters usually in a highly anti selective manner. Keywords: α,β-unsaturated esters; epoxyesters; fluorine; Grignard-based cuprates; nucleophiles; Introduction Fluorine-containing compounds have been utilized in diverse fields due to their special character

• t-BuO2Li reagent [31], we speculated that NaClO·5H2O would similarly work for the corresponding Z-1 with retention of stereochemistry. The procedure found here was also applied to the three representative CF3-containing α,β-unsaturated esters,1h–j [42] with different substitution patterns (Scheme 2

• spectra for the compounds 11a and 11a-D. Expectation of the regio- as well as stereoselective reactions of 2. Attempts of the present epoxidation to other α,β-unsaturated esters, 1h–j. Introduction of additional halogen atoms at the 2-position of the compound 2b. Clarification of the stereochemistry of

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol-type reactions, and reductive Mannich-type reactions using RhCl(PPh3)3 with Et2Zn [41][42][43][44][45][46][47]. The rhodium-catalyzed reductive aldol reaction of α,β-unsaturated esters with aldehydes or ketones gives aldol-type products in good to excellent yields (Scheme 1) [43][44]. In addition

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• full agonists (54 and 55, Scheme 20A) [139]. Ackermann and co-workers presented a manganese(I)-catalyzed C–H allylation, installing α,β-unsaturated esters in peptide analogues bearing indole motifs (Scheme 22B) [140]. Starting with tryptophan, the enantioselective allylation reaction afforded the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• major advantages of 17 over 12 are that the bromo derivative 17 is stable at room temperature and requires a lower temperature than 12 to decompose to difluorocarbene. By the use of BrCF2COONa in diglyme at 150 °C, various alkyl- and aryl-substituted alkenes, allyl alcohol esters, α,β-unsaturated esters

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• verified by mass spectrometric fragments missing 2 amu compared to saturated analogs (see Supporting Information File 1, Figure S5) [36]. Hydroxy and α,β-unsaturated esters were not observed during GC of synthetic samples, making an artificial formation during chromatography unlikely. In addition to the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ketones, a 1,4-addition product was formed through a transient copper enolate, 157. With α,β-unsaturated esters, however, a carbon enolate, 160, is the intermediate. In order to maintain a catalytic cycle, iPrOH could be added to regenerate the active Cu species (Scheme 28). This study again proofed that

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• , Sapporo, Hokkaido 001-0021, Japan 10.3762/bjoc.16.50 Abstract A chiral phenol–NHC ligand enabled the copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters. The phenol moiety of the chiral NHC ligand played a critical role in producing the enantiomerically enriched products. The

• generated copper hydride in situ, has successfully been utilized for enantioselective reactions with β,β-disubstituted α,β-unsaturated carbonyl compounds [4][5][6][7][8][9][10][11]. The pioneering work of Buchwald and co-workers on the enantioselective conjugate reduction of α,β-unsaturated esters using a

• ligand on the copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with hydrosilanes, placing a focus on (Z)-isomer substrates, which generally gave slightly lower enantiomeric excess with the chiral bisphosphines compared to the (E)-isomer substrates. Results and Discussion

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• report the ECA of Grignard reagents to α,β-unsaturated thioesters [25]. Advantageously, the latter were also readily accessible but significantly more reactive than α,β-unsaturated esters. Indeed, the thioester fragments featured a reduced electron delocalization compared to oxoesters, which resulted in

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• acids. In 2014, a Cu(I/II)-catalyzed α-trifluoromethylation of α,β-unsaturated carbonyl compounds were unfolded by the Bi group (Scheme 77) [140]. The reaction was applied to a broad range of carbonyl compounds, including enones, α,β-unsaturated esters, thioesters, and amides. Notably, the authors

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• Information File 1 for full experimental details). Both derivatives 9 and 10 (Scheme 2) yielded α,β-unsaturated esters 12 and 13 after treatment with Martin sulfurane [16]. Reduction of compound 12 using NiCl2/NaBH4 in methanol as solvent yielded derivative 14 with excellent diastereomeric ratio (dr = 1:0.03

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• , respectively, were tolerated in the reaction. However, substrates such as 4-methoxystyrene or styrene did not yield the desired products. The same Rh-catalytic system proved to be applicable to the carboxylation of α,β-unsaturated esters 38 (Scheme 34). A variety of substrates 38a–f, including those containing

• -catalyzed C(sp2)–H carboxylation of 2-arylphenols 34. Hydrocarboxylation of styrene derivatives with CO2. Hydrocarboxylation of α,β-unsaturated esters with CO2. Asymmetric hydrocarboxylation of α,β-unsaturated esters with CO2. Proposed reaction mechanism for the Rh-catalyzed hydrocarboxylation of C–C double

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• examples, we showed that it is possible to extend the presented procedure to the reaction of dithiolanylium TFB with other Michael acceptors as, e.g., α,β-unsaturated esters 12a or 12b (yielding 13a and 13b, Scheme 5). The reaction proceeded under similar conditions as shown in Table 1 (the reaction

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• direct synthesis of β-lactams by reductive Mannich-type reactions [14][18][19][20][21]. We recently reported a reductive Mannich-type reaction using a combination of RhCl(PPh3)3 and Et2Zn to give the corresponding syn-β-lactams from α,β-unsaturated esters and imines in good to excellent yields together

• . However, some of the reactions using β-substituted α,β-unsaturated esters did not afford the products or gave the products in very low yield (Scheme 2). Herein, we report an expansion for our previous reductive Mannich-type reaction and mechanistic studies for the stereoselectivity of this reaction

• . The results from the reaction of the [RhCl(cod)]2 catalyst with various α,β-unsaturated esters are summarized in Table 1. Most of the synthesized β-lactams were obtained with dramatically improved yields, although the β,β-disubstituted α,β-unsaturated ester did not give the product owing to the

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• and methyl vinyl ketone and α,β-unsaturated esters [44]. Trost and co-workers orchestrated the only example of the enantioselective reaction of D–A cyclopropanes with C=C double bonds with Meldrum’s acid and alkylidenes or azlactone alkylidenes, catalyzed by the chiral Trost Pd(0)-complexes [45

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• hydrogen atom transfer are also included in this review. Review α,β-Unsaturated esters Lewis acids α,β-Unsaturated esters have been the most extensively studied class of electrophiles for conjugate addition–enantioselective protonation sequences. Esters are useful functional group handles for additional

• synthetic manipulations. Furthermore, enantioselective conjugate additions to α-amino-α,β-unsaturated esters provides rapid access to enantioenriched α-amino acid derivatives. However, α,β-unsaturated esters present some challenges; the transient enolate intermediate can adopt E- or Z-enolate geometries

• aldehydes and α,β-unsaturated esters (Scheme 8) [25][26]. Catalyzed by triazolium NHC-catalyst 35, electron-poor and neutral aromatic aldehydes reacted with methyl 2-acetamidoacrylate to access α-amino esters 34a with excellent enantioselectivity [25]. As expected, less electrophilic 4-methoxybenzaldehyde

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• doesn’t change after the addition of nitrostyrene. 1.2.2 α-Silyloxyenones as acceptors. Among Michael acceptors, simple α,β-unsaturated esters and amides still are challenging substrates in direct Michael additions and have only been employed in few successful Michael reactions, mainly due to their

Synthesis of α,β-unsaturated esters via a chemo-enzymatic chain elongation approach by combining carboxylic acid reduction and Wittig reaction

• Yitao Duan,
• Peiyuan Yao,
• Yuncheng Du,
• Jinhui Feng,
• Qiaqing Wu and
• Dunming Zhu

Beilstein J. Org. Chem. 2015, 11, 2245–2251, doi:10.3762/bjoc.11.243

• /bjoc.11.243 Abstract α,β-Unsaturated esters are versatile building blocks for organic synthesis and of significant importance for industrial applications. A great variety of synthetic methods have been developed, and quite a number of them use aldehydes as precursors. Herein we report a chemo-enzymatic

• chain elongation approach to access α,β-unsaturated esters by combining an enzymatic carboxylic acid reduction and Wittig reaction. Recently, we have found that Mycobacterium sp. was able to reduce phenylacetic acid (1a) to 2-phenyl-1-ethanol (1c) and two sequences in the Mycobacterium sp. genome had

• aromatic and aliphatic carboxylic acids, including ibuprofen. The Mycobacterium CAR catalyzed carboxylic acid reduction to give aldehydes, followed by a Wittig reaction to afford the products α,β-unsaturated esters with extension of two carbon atoms, demonstrating a new chemo-enzymatic method for 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

• and Michael addition, followed by a Wittig reaction [19][20]. Although the utility of the Bestmann ylide in the synthesis of acyclic α,β-unsaturated esters and dienamides has already been reported [11][13][16], its application to the synthesis of α,β,γ,δ-unsaturated esters (i.e., dienoates) remains