Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• followed by lactonization to Int-21 and Int-22 (Scheme 11c). Chi and co-workers showed that desymmetrization of urazoles can lead to axially chiral derivatives [31]. The NHC-catalyzed (3 + 2) annulation between α,β-unsaturated aldehydes 36 and urazoles 37 generates atropoisomers 38 with a C–N stereogenic

• benzofuran-3-carbaldehydes 50 (Scheme 16). Another demonstration of the atroposelective formation of compounds with a C–N stereogenic axis was developed by Jindal, Mukherjee, Biju, and co-workers [36]. The authors developed an NHC-catalyzed desymmetrization of N-aryl maleimides 53, which afforded a range of

• -Breslow-type intermediates with the chiral NHC-catalyst and subsequent deprotonation toward the nitrile product. Zhang, Wang, Ye, and co-workers utilized NHC-catalysis for the atroposelective synthesis of axially chiral diaryl ethers 59 and 61 [38]. This transformation was realized via desymmetrization of

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• , Ballester and co-workers reported on the preparation of an octapyridinium-based water-soluble superaryl-extended calix[4]pyrrole molecular container and used it as a capsule for desymmetrization reactions [41], where the reported compound acts both as sequestering and supramolecular protecting group. All of

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• observed (Table 3, entries 9 and 10). 4-Pyridylboronic acid pinacol ester (25) was also attempted; however, no product was formed. Vinylboronic acid ester 22, was also explored as a substrate, with multiple porphyrin products being observed by TLC and by 1H NMR. Desymmetrization of the porphyrin was also

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• terazosin and prazosin were successfully synthesized. Oliveira Jr. et al. developed a new methodology for the asymmetric synthesis of β-aryl-γ-lactam derivatives with very good yield and enantioselectivity [16]. This was achieved through a palladium-catalyzed Heck–Matsuda desymmetrization of N-protected 2,5

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• was shown that subsequent ring opening can be triggered by the addition of electron-deficient ketones or boronic acids, which resembles a novel strategy for azetidinol desymmetrization. The nature of the protecting group was found to be critical for the two-step process to be effective, which resulted

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• potentially useful molecules. Keywords: Cannizzaro reaction; crossed-Cannizzaro; desymmetrization; Lewis acid catalyst; natural products; Introduction The synthesis of functionalized molecules with structural complexity has always been a challenge to synthetic chemists. The Cannizzaro reaction, in its

• -transfer catalyst in the presence of KOH as the base. Canipelle et al. [28] put forward an improved Cannizzaro disproportionation of 4-biphenylcarboxaldehyde into the corresponding alcohol and carboxylic acid products employing cyclodextrins as the phase-transfer agent. A Cannizzaro desymmetrization

• methodologies, such as Lewis acid catalysis, desymmetrization of symmetrical dialdehydes, synthesis of natural products, and building blocks. These modifications constitute the main highlight of this review. The use of modern technology and newer strategies aiming towards industrial benefit is the goal for the

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

• commercial drug baclofen as hydrochloride. Keywords: desymmetrization; enantioselective Heck–Matsuda reaction; lactam synthesis; N,N-ligands; palladium; Introduction Desymmetrization reactions consist in the modification of a molecule with the loss of one or more symmetry elements, such as those which

• complexity in a synthetic route. The palladium-catalyzed coupling of arenediazonium salts with olefins, the Heck–Matsuda reaction, has been instrumental in this strategy involving the desymmetrization of cyclic systems [3], especially five-membered substrates [4][5][6][7]. As we have demonstrated previously

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

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

• . presented their work on the asymmetric desymmetrization of cyclopentene-1,3-diones 5 (Scheme 3) [23]. Following the Cu(OTf)2-catalyzed conjugate addition of R2Zn, the enolate 6 was trapped by several aromatic aldehydes 7. These complex chiral cyclopentane derivatives 8 bearing all-carbon quaternary

• enantioselective tandem borylation/intramolecular aldol cyclization procedure (Scheme 37) [78]. The desymmetrization process of cyclic diones 147 gave the densely functionalized bicyclic products 148 with four contiguous stereocenters usually in a highly diastereoselective fashion. Presumably, the difference in

• desymmetrization step during which the chiral enolate attacks (Si-face) the prochiral cyclohexadienone ring via a chair-like transition state. The reaction requires an excess amount of base, resulting in the formation of a more favorable lithium enolate. Subsequent oxidation of the boronates gave the corresponding

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

• Morgan Cormier Florian Hernvann Michael De Paolis COBRA, Normandie University, 76000 Rouen, France 10.3762/bjoc.18.183 Abstract A convergent approach to the skeleton of tridachiapyrone B is described taking advantage of the desymmetrization of α,α’-dimethoxy-γ-pyrone leading to α-crotyl-α

• -pyrone by desymmetrization of α,α’-dimethoxy-γ-pyrone 2 through the addition of hindered nucleophiles to construct the vicinal quaternary carbon. In a subsequent and potentially enantioselective desymmetrization step, compound 5 would be converted into trichiachiapyrone B by 1,4-addition of the side

• yield was actually noted with (PhSe)2 as electrophile, 5 being obtained in 62% yield, enabling thus an evaluation of the next desymmetrization step. An overview of the scientific literature revealed that, while the asymmetric desymmetrization of prochiral 2,5-cyclohexadienones is a rich topic of

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• desymmetrization of the molecule caused by a partial and reversible self-inclusion of the triazole moiety into the CD cavity, as was previously studied in detail for the CD dimers prepared by CuAAC reaction [15]. Although such self-inclusion was not prominent for dimers based on the short propargyl ether linker

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

• thread also leads to a desymmetrization of the BINOL-based macrocycle (loss of C2 symmetry), as seen by 13C NMR spectroscopy. Stoddart and co-workers also used their π–π-recognition approach for the synthesis of BINOL-containing cationic catenanes [47][48]. They employed BINOL-based macrocycles

• desymmetrization of meso-1,2-diols [58]. The [2]rotaxane (R)-42 was synthesized by interaction of the ammonium salt 41 with the BINOL-based macrocycle (R)-12 and end-capping with 3,5-di-tert-butylbenzoic acid (see Figure 10). In the asymmetric desymmetrization reaction of meso-hydrobenzoin, rotaxane (R)-42 gave

• desymmetrization reaction of meso-1,2-diols with rotaxane (R)-42. Synthesis of Niemeyer´s axially chiral [2]catenane (S,S)-47. Results for the enantioselective transfer hydrogenation of 2-phenylquinoline with catalysts (S,S)-47, (S)-48, and (S)-49. Synthesis of Niemeyer´s chiral [2]rotaxanes (S)-56/57. Results for

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• greatly differ, as described by Allen and co-workers in their 2007 report on rhodium-catalyzed cyclodimerization reactions [59]. Moreover, desymmetrization of OBD produces more unique sites of reactivity allowing for the production of regioisomeric products. In 2019, Deng et al. described syn

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

• central chirality information to the axial chirality to give the chiral biaryldiols (Scheme 3) [14]. In 2013, Akiyama and co-workers described the enantioselective preparation of multisubstituted biaryls by the desymmetrization strategy, which was further enhanced by the subsequent asymmetric reaction

• (kinetic resolution) in the presence of chiral phosphoric acid CPA 3. In this work, various EWG- and EDG-containing substrates were incorporated, and chiral biaryls 10 were obtained with good to excellent selectivities of 81–93% ee by desymmetrization and 63–96% ee by kinetic resolution. The subsequent

• discovered in 2019 a highly effective approach using organocatalytic atroposelective desymmetrization and kinetic resolution to obtain enantioenriched axially chiral arylpyrroles. The axially chiral arylpyrroles 73 were prepared in high yields (up to 99%) and with excellent enantioselectivities (up to 98% ee

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• , desymmetrization of 86 was achieved under Sharpless epoxidation conditions employing a t-BuOOH/(+)-DIPT/Ti(O-iPr)4 system to give epoxide 85 (63%), which was subsequently protected as PMB ether 84 in 86% yield (Scheme 10). In parallel, the same precursor 86 was subjected to another Sharpless epoxidation using

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• example utilizing this strategy was provided by Jacobsen and co-workers for the desymmetrization of meso-aziridines 29. In their work, the bifunctional phosphinothiourea catalyst 31 promoted the C–N bond cleavage by hydrochloric acid upon initial protonation (Scheme 7) [55]. Subsequently, the catalyst

• -bound chloride anion performs a SN2-type attack on the coordinated benzoyl-protected aziridine, which leads to a formal addition of HCl. This concept was further developed and successfully employed by Ooi in the desymmetrization of meso-aziridines 32 with TMSX as chloride and bromide with similar

• performances as nucleophile precursors using a triazolium-amide chiral catalyst 34 [21] (Scheme 8a), as well as by Jacobsen in the desymmetrization of oxetanes 35 using TMSBr and squaramide 37 as catalyst [56] (Scheme 8b). For the latter, a more detailed mechanistic study was recently provided [57]. The

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• of cyclopentene-1,4-diol that was obtained by the enzymatic desymmetrization of the corresponding diacetate, an enyne metathesis precursor was accessed by a Mitsunobu-type coupling reaction with propargylic amide. The ring-rearrangement metathesis (RRM) of this enyne precursor was carried out using

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• stereoselective manner, given that corresponding chiral substrates were used for the cyclization. The chiral compounds suitable for cyclization could be obtained by desymmetrization of phosphine sulfides (Scheme 3) [58]. In order to gain insight into the cationic cyclization of β-hydroxyalkylphosphine sulfides, a

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• , respectively), in agreement with the NMR findings (see Section 4 in the Supporting Information File 1). The apparent desymmetrization of 2 is not manifested by multiplication of signals due to H1 and H4, which can be attributed to the dynamic fluctuations of the cage in solution. We have previously noted that

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• spectroscopy (see Figure S1 in Supporting Information File 1). These results show that “desymmetrization” of DAEs still represents a real synthetic challenge. Diiodides 5 and 8 provide the possibility [9][10] to obtain symmetric DAEs, and monoiodides 4 and 7 allow for a short and straightforward approach

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• employment of halide additives had always a beneficial effect on the enantioselectivity [55]. The product ring size dependence observed in the desymmetrization of 166, 168 and 170 with 164 was explained considering that an NHC rotation is possible during the catalytic cycle and that 166, 168 and 170 should

• and 172 in the desymmetrization of 166 and 170 were comparable. This suggested that the reaction occurs faster when the N-methyl group is syn to the ruthenium–carbene than when the N-aryl group is located syn to the ruthenium–carbene moiety. In order to try suppressing the NHC rotation during the

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• ranged from –78 °C to room temperature. The use of amines, alcohols as well as alkyl and arylthiols as nucleophiles failed to provide the corresponding products. A year later, Antilla and co-workers found lithium-binol phosphate 64 to be an efficient catalyst for the desymmetrization of meso-epoxides

• ) with MS 4 Å. Asymmetric ring opening of meso-epoxides by p-xylenedithiol catalyzed by a (S,S)-(salen)Cr complex. Desymmetrization of meso-epoxide with thiophenol derivatives. Enantioselective ring-opening reaction of meso-epoxides with ArSH catalyzed by a C2-symmetric chiral bipyridyldiol–titanium

• complex. Enantioselective ring-opening reaction of stilbene oxides with ArSH catalyzed by a C2-symmetric chiral bipyridyldiol–titanium complex. Asymmetric desymmetrization of meso-epoxides using BINOL-based Brønsted acid catalysts. Lithium-BINOL-phosphate-catalyzed desymmetrization of meso-epoxides with

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• )-GABOB. Keywords: alcoholysis desymmetrization; bifunctional organocatalysis; chloramphenicol base; Introduction Over the past decade, remarkable advances in the utilization of natural products as chiral structural motifs for the design of bifunctional organocatalysts have been achieved. A high

• desired bifunctional Brønsted acid/base reactivity for enantioselective desymmetrization of anhydrides [48][49]. Results and Discussion A series of new chloramphenicol based-amide bifunctional catalysts 7a–q (Scheme 1) were synthesized from the appropriate optically pure (1R,2R)-diamine 6, prepared via

• desymmetrization of meso-cyclic anhydrides. This method proved to be generally applicable on various anhydrides or alcohols to generate the desired monoesters in good yield and enantioselectivity. The application of this method to the synthesis of (S)-GABOB demonstrated the great synthetic potential for

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• enabled the quantitative synthesis of (thio)ureas and guanidines without using bulk solvents and the generation of byproducts, but it has also been established as a means to develop "click-type" chemistry for these classes of compounds and the concept of small molecule desymmetrization. Moreover

• of para-phenylenediamine (p-pda) where steric hindrance is absent, the desymmetrization was more challenging. It was only achieved in 97% 21a in the reaction with less reactive 4-methoxyphenyl isothiocyanate under NaCl dilution and LAG using ethyl acetate. When highly reactive 4-nitrophenyl

• -thiourea 21a with 4-chloro- and 4-nitrophenyl isothiocyanates. This study demonstrated that solid-state ball milling can efficiently be employed for desymmetrization of ortho- and para-phenylenediamines, enabling selective functionalization of small symmetrical molecules through the extension of molecular