Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• 50 mmol scale [60]. Little racemization (<7%) of 77 occurred during the reaction. The simplicity of the Kropp protocol resulted in a report in the journal of chemical education [61]. Similar work was reported by Delaude and co-workers [62]. They studied a series of zeolites for the hydrochlorination

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• isomerization and photochemical (only for 13a) isomerization [46]. Compounds 13 showed intrinsic planar chirality and their enantiomers could be separated by HPLC. Notably, upon thermal and photochemical isomerization of these compounds, no Z-isomers were detected and only the racemization took place. Such

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• in the visible region were evident in their CD spectra. Using the Arrhenius and Eyring formalisms, the kinetic parameters for the thermal racemization of 57 and 58 were obtained. The activation free enthalpy (ΔG‡) for the racemization of 57 (ΔG‡298 K = 24.8 kcal mol−1) was ≈1.5 kcal mol−1 larger than

• determined the absolute configurations of these atropisomers through the X-ray crystallographic analyses of (Sa)-59 and (Ra)-60. Surprisingly, heating the enantiomers of 69 and 60 at 80 °C for 3 h resulted in negligible thermally induced racemization. Meanwhile, in O2-free toluene solution under illumination

• , the racemization was observed at 80 °C. Torres et al. performed detailed theoretical calculations and showed that the racemization observed in 59 and 60 is caused by triplet-state photogeneration, which leads to the rotation around the sterically hindered buta-1,3-diene chiral axis [132]. In fact, the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• has been used to cure a liquid isoprene polymer in precise digital light processing 3D printing [105]. Recently, Kanbayashi et al. reported that thiol–ene chemistry would not cause racemization of an asymmetric center linked to a pendant vinyl group, which can be particularly valuable for

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• reacted immediately (one-pot procedure) with sodium borohydride to give 4.4. It must be noted that this sequence does not induce racemization and that 4.4 can be stored for months with 0.5% of solid KOH acting as a stabilizer [72]. Then, 4.4 was alkylated with stearyl tosylate to produce 4.5. The two

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• chiral nanographenes. Keywords: chiral nanographene; helicene; racemization barrier; Scholl reaction; single-crystal X-ray diffractometry; Introduction Graphene, an allotrope of carbon, has captured widespread attention since it was first experimentally demonstrated as a monolayer of carbon atoms [1

• determined for the enantiopure helicenes. For compound 12, the racemization barrier was 24.8 kcal mol−1 at 298 K, which provides a racemization half-life (t1/2) of 24.4 h. For compounds 11 and 13, neither racemization nor decomposition was observed by chiral HPLC after heating hexadecane solutions of each

• compound at 200 °C for 5 h, which gives a lower limit to the barrier of racemization of ΔG > 38.3 kcal mol−1 at 473 K. The circularly polarized luminescence (CPL) of these structures were also evaluated with the luminescence dissymmetry factors (glum) values of 4 × 10−4 for compound 11 and 7 × 10−4 for

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• chirality which exhibits no racemization under action of strong bases [29]. The chiral N–H-containing rimantadine-based ligand (L6) is highly lipophilic and it was successfully used for the kinetic resolution of unprotected racemic amino acids [30]. The examples mentioned above show that the metal–Schiff

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• rotation of the isolated products 43a–h did not show any racemization under the standard reaction conditions. Thereafter, imidazolium salts 45a–d, obtained from imidazole N-oxides 44a–d, provided the desired optically active 3-butoxyimidazole-2-thiones 47a–d in 66–83% yield using triethylamine in pyridine

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• . Ultimately, enantiomeric purities of >99% ee were reached for both 6a and 6b (Figure S4, Supporting Information File 1). The compounds were subsequently converted into the diphosphates. To exclude partial racemization during this conversion, small samples of each enantiomer of 2-Me-LPP were dephosphorylated

• available, and their conversion into the enantiomers of 2-Me-LPP proceeds without noticeable racemization, leading to materials of >99% ee. Incubation of both pure enantiomers revealed that (R)-2-Me-LPP is the on-pathway intermediate towards 1, while its formation from (S)-2-Me-LPP may be explained through

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• yield when HATU/DIPEA as the coupling reagent was used (Table 1, entry 2). Only trace product could be detected with EEDQ (Table 1, entry 4). Further screening did not give better results (Table 1, entries 5 and 6). The purity of tripeptide 7 was determined by HPLC and no racemization was observed

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

• good yields (24 to >99%) with poor to moderate ee (9 to 55%). A complete reversal of stereoselectivity was observed on introducing a benzoyl group in cinchonine and cinchonidine. It was demonstrated that racemization occurred in suitable solvents under mild conditions due to retro-MR of the initially

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• enantioselective synthetic strategies towards 2,3-dihydroquinazolinone derivatives has drawn the attention of organic chemists for a long time [14][15][16][17][18], even though the aminal stereocenter is sensitive to racemization [12]. The well-established and straightforward approach in the asymmetric

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• alkynylations of bioactive structural motifs are rare [63]. In 2017, the Ackermann group disclosed a late-stage Mn(I)-catalyzed C–H alkynylation of various complex peptide scaffolds [64]. As shown in Scheme 9, manganese(I) catalysis remarkably resulted in racemization-free alkynylation, representing a step

• ]. Based on an initial optimization study, manganese(I) pentacarbonyl bromide was deemed as the optimal catalyst, enabling a robust racemization-free allylation process. In addition to tryptophan-containing peptides, diazepam and nucleoside analogues were found to be viable allylation substrates, affording

• , a natural product scaffold, was transformed into glycosylated tryptophan 31f. It is noteworthy that this manganese(I)-catalyzed glycoconjugation method avoids racemization. Furthermore, manganese-catalyzed allylative linchpin C–H glycosylation was investigated using structurally sophisticated

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

• major drawbacks identified with the Prins cyclization are the racemization due to competing oxonia-Cope rearrangement and side-chain exchange. Willis and co-workers studied the reactivity of the Prins reaction of different aryl group-substituted homoallylic alcohols 18 with propanal in the presence of a

• % yield and <5% ee. The poor enantiomeric excess of the product 23 indicates that the racemization takes place during the course of the reaction. It was explained that the reason for the loss of optical purity was due to the formation of a benzylic cation, which is stabilized by the electron-rich aromatic

• propanal, which proceeded with high selectivity to give the corresponding THP 28 (79% ee, 32% yield) along with some recovered starting material (47%), as shown in Scheme 6. Partial racemization was also reported at the same time by reversible 2-oxonia-Cope rearrangement and via side-chain exchange [31][32

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• , indicating a racemization during the reaction process. The less polar isomer with R-configuration [31][32] at C2 showed a complete loss of β-lactamase inhibition activity as compared to the more polar isomer. Therefore, the less polar isomer was discarded while saving the more polar S-isomer, (relative ratio

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• followed by oxidation. The corresponding phosphinyl depsipeptides 107 were generated and further oxidized into phosphonyl depsipeptides 108 (Scheme 17) [32]. The protected phosphonodepsidipeptides 111 were prepared without racemization from N-Cbz-protected α-aminoalkylphosphonic monomethyl (12h) or benzyl

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• occurred with 41% inversion (and 59% racemization, i.e., product 23f was obtained with an enantiomeric ratio of ca. 70:30 in favor of the (S)-enantiomer), while complete racemization was observed in more ionizing TFA or HFIP as the solvent (Figure 5b) [48]. These observations are in agreement with a

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