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

• by a dipolar resonance structure containing the 2-fluoroallyl cation and fluoride anion (Scheme 39). A subsequent comparison of the rates of racemization with those of epimerization confirmed experimentally the preference for coupled disrotatory motions in the opening and closing of 2,3-dialkyl-1,1

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• solvent screening showed that the target product could be obtained in 95% ee catalyzed by 3 in CHCl3 (Table 1, entry 4). However, acidic and basic additives [23][24] resulted in a decrease of the enantioselectivity (Table 1, entries 10–12), or even to racemization in the case of TFA (Table 1, entry 13

• explains that more polar or protic solvents and strong acidic additives also destroyed the H-bondings resulting in decreased enantioselectivities or even racemization (Table 1, entries 7 and 13). Conclusion In summary, a new phosphoric acid bearing two free hydroxy groups was synthesized based on a highly

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• , 101c, and 107 [60][61] (Scheme 23). Following the previous method, the chiral auxiliary 108 was readily cleaved under mild acidic conditions to afford the hydrochloride salt of 3,4,5-trifluoro-Phe 109 in 86% yield and 95% ee, indicating very low racemization [62] (Scheme 24). 1.10. PAM enzymatic

• with LiBH4 resulted in alcohol 124 which was oxidized by Dess–Martin periodinane to give (S)-(−)-2-fluoro-2-phenylacetaldehyde (125). This aldehyde is prone to racemization and decomposition and therefore was directly converted to the arylidene derivative 127, by treatment with p-toluenesulfinamide

• 148 in variable yields with partial racemization. Phthalimido and trifluoroacetyl N-terminal protecting groups (R1 = Phth or TFA) and unprotected C-terminal derivatives (R2 = H) provided the most efficient outcomes (80 and 67% yield, respectively). An N-acetyl group was also suitable as protecting

Bipyrrole boomerangs via Pd-mediated tandem cyclization–oxygenation. Controlling reaction selectivity and electronic properties

• Liliia Moshniaha,
• Marika Żyła-Karwowska,
• Joanna Cybińska,
• Piotr J. Chmielewski,
• Ludovic Favereau and
• Marcin Stępień

Beilstein J. Org. Chem. 2020, 16, 895–903, doi:10.3762/bjoc.16.81

• of cNMI3O could not be separated, presumably because of very rapid racemization. The half-life time of cNDA3O enantiomers (ca. 0.54 min) was too short to record their CD spectra, but was long enough for a kinetics study (Supporting Information File 1, Figures S8 and S9). Enantioenriched samples of

• measurements, without any significant loss of the unpolarized emission intensity. This behavior, which precluded a quantitative analysis of the CPL properties, may be attributed to a photoinduced racemization process. The differences in configurational stability of boomerangs are reproduced by DFT calculations

• emitters, provided that their helicene-like twist is further stabilized against racemization. Efforts to achieve this goal are currently ongoing in our laboratory. DFT-Optimized structures (B3LYP/6-31G(d,p)) of cNDA2O and cNMI3H. Absorption and emission spectra of cNMI2H (top) and cNMI3H (bottom) measured

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• ’-binaphthyl backbone as precursors for the dehydrogenative coupling reaction (Scheme 2). In general, functionalization of the BINOL hydroxy groups should be performed at temperatures below 80 °C to prevent racemization [40][41]. 6,6’-Di-tert-butyl-1,1’-bi-2-naphthol (1) was treated with 2,6-difluoropyridine

[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

• for β-hydroxyalkylphosphine oxides [56][57], this led to the formation of cyclic phosphine oxides 3 and 26 rather than phosphine sulfides. It may be assumed that hydrolysis of the P=S bond occurred under these reaction conditions and, probably, racemization of the phosphorus center in the case of

• appeared to be quite low due to the significant racemization of the phosphorus center under the applied conditions. On the other hand, the treatment of (SP)-60 with Lewis acid led to the formation of chiral γ-mercaptoalkylphosphine oxide 46 in good yield and with only slight decrease in enantiomeric excess

• migration may have been a stereospecific process. What was more striking, the complete racemization of (SP)-65 and the extended racemization of (SP)-17 occurred under the reaction conditions. This suggested that the rearrangement may have proceeded either via two different pathways, or one of the reaction

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• imides and no racemization was observed during the reaction (Scheme 50). In 2000, Pilli and co-workers published a vinylogous Mannich addition of silyloxyfuran to chiral N-acyliminium ions generated in situ from 157 which had been obtained from the anodic oxidation of 156 bearing a cyclohexyl-based

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• racemization, alternative three-carbon chirons would be of great value in enantioselective syntheses of natural compounds and/or drugs. This review article summarizes applications of N-(1-phenylethyl)aziridine-2-carboxylates, -carbaldehydes and -methanols in syntheses of approved drugs and potential

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• and 10.0 min, respectively, demonstrating that P5A-DPA was the racemic mixture of Rp and Sp configuration. The two fractions were collected separately and re-injected into the chiral column to confirm the enantiomeric purity and to check if racemization of the enantiomers takes place in solution at

• room temperature. In both cases, only the original peak was detected and the peak for the antipodal enantiomer was not detected, indicating that no racemization of the enantiomer of P5A-DPA takes place at room temperature (Figure 3b and c). P5A-Py showed a similar phenomenon (Figure S22a,b and c

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• achieved via high-performance liquid chromatography (HPLC) on a chiral stationary phase. This approach is a promising alternative to the previously reported resolution through formation of diastereomeric esters because it involves fewer synthetic steps and is less prone to thermal (re)racemization. During

• these studies an intermediate saddle conformer could also be isolated and characterized by 1H and 13C NMR spectroscopy. The HPLC separation method was further developed in order to allow investigations on the racemization behavior of the cyclotriveratrylene derivative. Keywords: chiral resolution

• ; cyclotriveratrylenes; HPLC; macrocycles; racemization; saddle isomer; Introduction Cyclotriveratrylenes (CTVs) [1][2][3][4][5][6][7][8] are cyclic bowl-shaped molecules and belong to the most studied concave host molecules in supramolecular chemistry besides, e.g., calixarenes and resorcinarenes [9], cyclodextrins

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• solution, but also as a result of dynamic equilibrium between the Michael/retro-Michael products. This assumption is confirmed by a partial racemization of sulfones 8 at a prolonged storage, passing both the stereocenter at position 2 and the stereocenter at the position 3 (according to the HPLC data

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• isocyanide 57 and acetic acid, followed by reaction of the resulting formamide with triphosgene (Scheme 12). Compound 58 was obtained as a 78:22 diastereomeric ratio without any racemization of the pre-existing stereocenter and then used in the key step Ugi-type 3CR with cyclic imine 59 (generated in situ

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• ). For the synthesis of organozinc homoenolate 8, the MnBr2/CuCl-catalyzed reaction of diethylzinc with β-bromopropionic acid ester 19 in DMPU proved to be the best choice [42]. Racemization was avoided. The PMP protecting group was removed (CAN) affording methyl ester 7 (82%, Scheme 3). For comparison

• . Boc protection yielded N-Boc-D-3-iodotyrosine (21), which underwent three-fold methylation to N-methyl-O-methyliodotyrosine methyl ester 22 (82% yield, er 4:1, CHIRALPAK® IA, hexane/iPrOH 9:1). Partial racemization of 21 could not be suppressed since a slight excess of base was always necessary

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• )-2 and (2S,3S)-2 in several steps including hydroxymethyl to carboxyl oxidations (Scheme 2) [50]. N-Fmoc protection of the amino group in L-serine together with transformation of the carboxylic function into an orthoester allow for the racemization-free oxidation to aldehyde 10, which was immediately

• acid [(2S,3S,4R)-4] was obtained as the hydrochloride. To avoid racemization at Cα in sensitive amino acids the carboxy group was frequently masked as an orthoester. To illustrate this strategy dihydroxylation of the orthoester 92 (derived from L-pyroglutamic acid [97]) was performed to afford a single

• decomposition of this stereoisomer including racemization at Cα. From pentose via 2,3-aziridino-γ-lactone In the so called “2,3-aziridino-γ-lactone methodology” [18][99][100] ribose (or lyxose) is used as a starting material [101][102] which is transformed into the lactone 95 in several steps [99]. Boron

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• and phosphine oxide. The oxocarbenium ion would then react with the NuO− anion in a SN1 mechanism. While this would lead to racemization under normal circumstances, in most carbohydrates, participation effects of neighboring groups in the vicinity (typically at the 2-position of the sugar ring) affect

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• presence of PPh3 [28]. In addition, the peptide coupling reaction proceeds without racemization in the absence of a racemization suppressant and iodosodilactone can be readily regenerated after the reaction. In order to further enhance the reactivity of iodosodilactone, we designed and synthesized a new

• ]. Compared with classical solution-phase peptide synthesis, the fast development of SPPS is mainly due to its short reaction time, high efficiency, low racemization, simple work-up and automation. In recent decades, various strategies, for example, native chemical ligation (NCL) [32] and serine/threonine

• ligation (STL) [33], have been reported to solve the problems occurred during the development of SPPS. Peptide synthesis in solution mediated by FPID/(4-MeOC6H4)3P is rapid (within 30 min) and efficient, at the same time the reactions proceed without racemization. Thus, it is possible and significant to

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• bearing an acrylamide group at the ortho-position of the benzene ring. Synthesis of parent chiral benzamides 6–8 The use of a stereoselective chiral auxiliary which could be incorporated and removed easily without racemization was crucial for the success of our strategy. These requirements prompted us to

• selective cleavage in mild acidic conditions without racemization (Scheme 4). Indeed, further cleavage of the α-methyl-para-methoxyphenyl chiral auxiliary in protected isoindolinones 4a–c, 4e and 5 resulted in the corresponding NH-free lactams 1a–c, 1e and 2 without any racemization (Scheme 4). A subsequent

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• , allowing a nucelophilic attack to occur from more trajectories, leading to a mixture of inversion (predominant) and retention products. (D) Fully solvated cation, where attack of the nucleophile can freely occur from either face, leading to racemization of the product in an SN1 reaction. We propose that

• (C) ion pairs. The partial racemization observed in Table 3 suggests that the solvent-separated ion-pair intermediate (C) is most likely the reactive species, as it would naturally lead to a partial racemization of the substrate stereocenter. When the activator was changed from HFIP to a mixed system

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• within a couple of days, even if stored at low temperature (4 °C). Therefore, the proline subunits easily undergo racemization under alkaline conditions. Binding properties of CAP Based on the previous results, we preliminarily tested the interaction of guests 1–12 with CAP−2. We observed that anions 1

• standard 1 M NaOH solution was added (i.e., 0.75 mL, 1.50 mL, 2.25 mL or 3.00 mL for CAP−1, CAP−2, CAP−3 and CAP−4, respectively). The suspension quickly turned into a clear solution, the volume of which was finally adjusted to 30 mL. The solution was used within few hours to avoid racemization of the L

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• -unsaturated imine are not reversible. Reversibility of the rearrangement would be fundamental for racemization of propargylamines, which is consequently improbable. However, even in the presence of strong bases like KOt-Bu or LDA, the propargylamide–allenylamide rearrangement could never be observed for

• approach. Electron-withdrawing substituents in the Cα-position induced an irreversible alkyne–allene-α,β-unsaturated imine rearrangement under mild basic conditions, which makes an alkaline racemization of propargylamines improbable. Altogether, a large set of propargylamines with various amino acid

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

• , racemization through bond rotation is negligible during further brominations [65]. Indeed, the rotational barrier of substrate 1a, calculated at the B3YLP/6-31G(d) level of theory, is only 7.6 kcal/mol; on the other hand, that of the monobrominated intermediate 1m is 19.0 kcal/mol (Scheme 5). However, this

• barriers of monobrominated compounds 1p and 1q (bearing methyl and isobutyl groups, respectively, on the amide moiety) are lower than that of 1m. Although racemization of 2b, the rotational barrier of which is 22.9 kcal/mol, was observed after a lot of months, it is enough slow to enable the immediate

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• an additional bromination reaction followed by Bagley’s modified Hantzsch condensation with the adequate thioamide to deliver the fully orthogonally-protected heterocyclic core of GE2270 along with avoiding racemization of stereogenic centers (Figure 1). Successfully applied last year by Yamagushi's

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• methanol [17] and cyclization was achieved under basic conditions using sodium ethoxide; the lactam was prone to racemization under strongly basic conditions, this was avoided by short reaction times with sodium ethoxide, and by avoiding strongly basic reaction conditions in subsequent steps. A key