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

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• resolution [42][43][44][45][46][47], desymmetrization [48][49][50][51][52][53][54], de novo annulation [55][56][57][58][59][60][61], and point-to-axial chirality transfer [58][59] (for reviews, see references [31][62][63]), motivated us to expand on the utility of this class of small-molecule catalysts. We

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• Matthew A. Horwitz Elisabetta Massolo Jeffrey S. Johnson Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA 10.3762/bjoc.13.75 Abstract We report a desymmetrization of cyclohexadienones by intramolecular conjugate addition of a tethered dithiane

• ; desymmetrization; dithiane; iminophosphoranes; organocatalysis; phosphazenes; Findings Desymmetrization has become a well-developed strategy for the construction of complex molecular frameworks [1][2][3][4][5][6]. Cyclohexadienones are multipurpose synthetic building blocks that have found a central role in

• desymmetrization methodologies. The functional groups present in these symmetrical molecules allow for a wide array of downstream transformations and they are all formed through a single reaction from cheap and readily available aromatic feedstocks [7][8][9][10][11]. These substrates have been successfully

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• be prepared from optically inactive meso-tartaric acid through a two-step reaction sequence. It involves a complete desymmetrization during an acid-catalyzed reaction with (+)-camphor and methyl orthoformate and the subsequent treatment of the formed methyl diester with α-phosphonate carbanion

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• diastereocontrol (dr >98:2). Subsequent enzymatic desymmetrization [91] using lipase Amano AK gave the enantiomerically pure acetate 36 in 81% yield (ee >99%). A further three transformations then delivered cis-solamin A (29). Crucial to the success of this approach and its high efficiency is that it takes

• be solved in future investigations. To date there is only a single report on an enantioselective oxidative cyclization of a 1,5-diene using permanganate together with a chiral counter ion. Other strategies use either a chiral auxiliary, a subsequent desymmetrization or start from a chiral 5,6

• cyclization approach to cis-solamin A. Total synthesis of cis-solamin A using a Ru(VIII)-catalyzed oxidative cyclization and enzymatic desymmetrization as the key steps. Donohoe´s double oxidative cyclization approach to cis-sylvaticin. Permanganate-mediated approach to cis-sylvaticin by Brown and co-workers

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• the thiourea group interact with one or two carbonyl groups of phenylbutenoate 2 (Scheme 5). Another catalytic reaction catalyzed by a primary amine-thiourea that leads to multiple chiral centers is the asymmetric desymmetrization of 4,4-disubstituted cyclohexadienones 5, using the Michael addition of

• prochiral ketones 35 or 36, catalyzed by a primary amine-thiourea 37 developed by Jacobsen. The proposed pathway is based on desymmetrization of 35 or 36 by an intramolecular Michael addition of the corresponding enamines to an α,β-unsaturated ester, to yield bicyclic or spiro-bicyclic products 38 and 39

• the stereochemical outcome of the reaction. The same year, two different groups utilized thiourea catalyst 57 to catalyze the desymmetrization of meso anhydrides 58 and 59 through a methanolysis reaction (Scheme 20 and Scheme 21). Chin, Song and co-workers utilized the catalyst in 5–10 mol % catalyst

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• reaction, the trifluoroacetamido moiety present in the ortho position of the aryl halides plays an important role in enantiocontrol (Scheme 15). Copper-catalyzed asymmetric aryl C–N coupling through desymmetrization and kinetic resolution strategies In the past, the asymmetric version of aryl C–N/O/S

• system through an “indirect” way, either by asymmetric desymmetrization or kinetic resolution [40][41][42][43][44]. In most cases, the enantioselectivities were not satisfactory. Recently, a copper catalytic system became another option toward asymmetric N-arylation reactions in term of improving

• enantioselectivity and efficiency. In 2012, Cai et al. [45] developed the first copper-catalyzed asymmetric intramolecular Ullmann C–N coupling reaction through a desymmetrization strategy. The reaction lead to the enantioselective formation of indolines and tetrahydroquinolines in high yields and up to >99% ee