Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• -workers found a reversal of enantioselectivity that can be controlled by choice of solvent, which they rationalized by invoking a solvent induced change in ion-pairs [6]. In another study by Agbossou-Niedercorn, Michon, and co-workers, they found that chiral alcohols do not impact enantioselectivity [7

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• excellent yield and enantioselectivity. Keywords: asymmetric organocatalysis; chiral Brønsted acid; 3,3-difluoroindoline; Hantzsch ester; transfer hydrogenation; Introduction The introduction of fluoro atoms into organic molecules can alter their lipophilicity, solubility, metabolic stability, and

• relatively strict reaction conditions (up to 150 bar H2). In 2022, Liu’s group reported an asymmetric hydrogenation of 3H-indoles catalyzed by a chiral Mn complex, which showed good yield and enantioselectivity [25]. In addition to metal catalysis for the enantioselective reduction, asymmetric

• , synthesized in situ from a chiral boron phosphate complex with water, for asymmetric indole reduction (Scheme 1b) [30]. The mild reaction conditions, low catalyst loading, and high enantioselectivity rendered this transformation an attractive approach to synthesize optically active indolines. However, these

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• diastereoselectivity ratio with exo/endo21/20 = 1.9 nearly doubled. The same was true for the enantioselectivity, which increased from 23% ee for control 20 to 55% ee for anion–π catalyst 21. These results were in support that stabilization of the intrinsically disfavored exo transition state VII on the polarizable

• surface of carbon allotropes can increase diastereo- and enantioselectivity of Diels–Alder reactions. The direct formation of 1,3-nonadjacent stereocenters is a topic of concern in asymmetric catalysis [67]. To explore compatibility with anion–π catalysis, the addition of ethyl 2-cyano-2-phenylacetate (28

• ) to 2-chloroacrylonitrile (29) was selected (Figure 5) [68]. In the presence of 5 mol % of the best fullerene catalyst 21, conversion into dicyanide 30 reached 72% within 5 days at ambient temperature [67]. While enantioselectivity was negligible, dr 5.3:1 was the best diastereoselectivity among all

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• ). Based on the literature [36], Meldrum’s acid has a low solubility in non-polar solvents, resulting in diminished enantioselectivity. Furthermore, in our case, the application of polar solvents would not be favorable due to the low solubility of the lipophilic organocatalyst in these solvents

• ) [37]. In a similar manner as the former Michael addition, a solvent screening was carried out in the previously well-established four solvents: CPME, 2-MeTHF, anisole, and toluene (Table 4, entries 1–4). Based on the solvent screening, high yields and good enantioselectivity can be achieved in anisole

• and toluene, while using 2-MeTHF drastically decreased the enantioselectivity. From the perspective of green chemistry, anisole would be more favorable, but toluene is also a distinctly better alternative to the other solvents (e.g., DCM) commonly used in Michael additions. Another critical aspect

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• , resulting in good to excellent yields and enantioselectivity. This groundbreaking work opened up new possibilities for the practical application of photoredox catalysis in large-scale industrial processes, as it provided a more accessible and cost-effective catalyst system that could be readily utilized for

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• sulfur reagents resulted in thiolated products 92 up to 99% ee, in the presence of quinidine as the organocatalyst (Scheme 38) [72]. For the study of enantioselectivity of products, different N-substituted oxindoles with H, Me, phenyl, and benzyl groups were investigated. As the size of N-protecting

• groups increased, the percentage of enantioselectivity decreased, where in the case of NH-oxindoles, the product was achieved with only 6% ee. Another sulfenylation at the 3-position of unprotected oxindoles with N-(phenylthio)phthalimide was reported by Feng et al. [73]. A chiral N,N′-dioxide-Sc(OTf)3

• with N-(arylthio)phthalimide 14 and N-chlorophthalimide (96) under phase-transfer conditions was developed by Maruoka and co-workers (Scheme 39) [74]. The presence of chiral bifunctional catalysts C and D with the amide, or sulfonamide moieties could improve the enantioselectivity. Also, the

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• . The hydrosilylation of aryl, alkyl, and cyclic ketones could be accomplished with excellent yields (Scheme 35) [48]. In 2011, Gawley and co-worker reported an excellent reactivity and enantioselectivity of a C2-symmetric NHC–Cu(I) complex for the catalytic hydrosilylation of a variety of carbonyl

• enantioselectivity, using NHC–Cu(I) complexes generated in situ from chiral imidazolium salts containing possible chelating functional group(s). For example, the conjugate addition of Grignard reagents to 3-methyl- and 3-ethylcyclohexenones in the presence of the C2-symmetric chiral NHC–copper complex catalyst

• use of an azolium salt with a sterically bulky alkyl substituent such as N-CHRR (e.g., NCHPh2 in 123) on the azolium ring results in a marked increase in the enantioselectivity of the ACA reaction. Thus, a new functionalized azolium salt 123 was prepared and used in combination with Cu(OTf)2 as

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• dihydropyrans (DHPs) and aldehydes in the presence of Zn(II) (Scheme 37) [102]. The method has good enantioselectivity and functional group tolerance and provides a practical and economical route towards a series of enantiopure α-substituted DHPs through CDC, through an in situ NaBH4 reduction two-step sequence

• may provide completely new insights into this issue. In addition, CDC reactions involving ether α-C(sp3)–H bonds are rarely enantioselective, although examples of enantioselectivity have been reported for some similar CDC reactions of amines, and future developments will undoubtedly bridge this

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• enantioselectivity. Keywords: acetaldehyde; acetaldehyde dimethyl acetal; cascade reaction; multicomponent reaction; organocatalysis; Introduction Multicomponent reactions (MCRs) are chemical processes that involve three or more compounds, in which the product contains all the atoms of the reagents, except for

• nitroalkene derivatives with low reagent excess and high enantioselectivity; this reaction represents the first step in the Enders triple cascade catalytic cycle. The use of acetaldehyde in a two-component cascade reaction was previously reported by Enders [27]; however, the scope of this reaction is limited

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• ) azide complex, reducing the iron catalyst back to the starting Fe(II) state. Organic azides can be formed in moderate to high enantioselectivity using this approach; however, the scope is largely limited to benzylic products, a result in line with Groves’ finding that benzylic acid substrates perform

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -substituted indoles. The authors also tried the reaction with C3-substituted indoles to functionalize the C2 position. However, a very low enantioselectivity was achieved in the latter case (Scheme 10) [35]. Lin and co-workers designed a planar chiral phosphoric acid containing a [2.2]paracyclophane moiety

• yields and enantioselectivity. The catalyst P13 was an even far superior catalyst than conventional BINOL and SPINOL-derived phosphoric acids. The substrate scope was investigated by varying substituents in the carbocyclic ring of indole 4. Changing the β-aryl and α-substituents in the styryl-derived

• as the nucleophile. This reaction afforded (bis(indolyl)methyl)benzenesulfonamide derivatives 43 but no promising enantioselectivity was achieved for most of the products (Scheme 12) [37]. In 2019, You, Yuan and co-workers reported another enantioefficient aza-Friedel–Crafts reaction between N

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• derivatives using HBF4 or CF3SO3H (see Supporting Information File 1 for more details). The corresponding tandem products were isolated in medium to good yields as mixtures of diastereomers and high enantiomeric purities were recorded for selected tandem products. The enantioselectivity of this reaction is

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• imines 25 (Scheme 6). The authors also demonstrated the enantioselective aminoalkylation, using chiral diamines as ligands. The introduction of chiral diamines in the metal complex produced the aminoalkylated products enantioselectivity with good ratio of enantiomeric excess. The plausible mechanism

• containing bioactive molecules (Scheme 10). To attain enantioselectivity a chiral phosphine oxide (43)-ligated Ni–Al bimetallic catalyst was used that was critical in improving the reactivity and controlling the selectivity of the reaction. Further, based on deuterium labelling experiments, KIE studies, and

• elimination delivers the desired product 44 via the intermediate 49 (Scheme 10b). It was proposed that the enantioselectivity was mainly due to the C–C reductive elimination of the R-pathway, which is lower in energy than the S-pathway. Remote C–H alkylation Several remarkable studies have been reported for

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• enantioselectivity of the three-component coupling of glyoxylic acid (employed as its solid, easy-to-handle monohydrate) with 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonylamide, and an arylboronic acid was significantly affected by the nature of the boronic acid. Whereas the reaction with phenylboronic acid

• afforded the Pbf-protected [23] phenylglycine derivative 10a in high yield and enantioselectivity, an almost racemic mixture of 10b was obtained from the corresponding (p-methoxyphenyl)boronic acid (2b, Scheme 2a). This decrease in enantioselectivity can be attributed to a faster racemic background

• increase in enantioselectivity. Decreasing the arylboronic acid to active catalyst ratio could be one possible opportunity to decrease the rate of the background reaction. Thus, we envisioned that this could be achieved by the slow generation of small amounts of the boronic acid from a suitable precursor

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

• using acyclic enones 14 [27]. Their tandem conjugate addition/Mannich reaction methodology offers access to various non-cyclic β-aminoketones 16 with multiple contiguous stereocenters in high diastereo- and enantioselectivity (Scheme 5a). Additionally, chiral isoindolinones 18 and 2,3,4-trisubstituted

• three-step reaction sequence resulting in trisubstituted nitropyrrolidinones 24 with exceptional enantioselectivity (Scheme 6B). In contrast to conjugate additions to nitroolefins, these activated alkenes can also be utilized in the enolate trapping step. In the last decade, several highly

• (diallylation) because the strongly basic R2Zn can form the enolate from the monoallylated product 32. Therefore, using only 1 equiv of dialkylzinc, the desired allylated products 32 were isolated in good yields and excellent diastereo- and enantioselectivity. Soon after, Jarugumilli et al. investigated the

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

• -Cl [21], 3,4-di-Cl [21][22], 2/3/4-F [23]) were inserted in the N-benzyl moiety as well as in the aromatic rings of the benzophenone fragment [24][25][26] (selected examples are given in Scheme 1). Insertion of halogen atoms increased enantioselectivity, e.g., in alkylation reactions [27][28

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• noted decreasing the steric bulk of the amide moiety of the substrate from isopropyl to ethyl to methyl decreased the enantioselectivity of the reaction. Carbon- and nitrogen-bridging bicyclic alkenes were also identified as competent substrates. In this respect, norbornadiene was found to give the

• desired carboaminated product in slightly diminished yields while azabicyclic alkenes generated the targeted products in excellent yield, albeit with slightly reduced enantioselectivity. To showcase the synthetic capabilities of this methodology, the authors synthesized the non-natural amino acid

• reduced yield and enantioselectivity. Bridgehead-substituted, non-benzo-fused oxabicycles, as well as azabicyclic alkenes failed to produce the desired product. When the benzo-fused moiety was unsymmetrically substituted, little regioselectivity was observed. Based on X-ray crystallographic data for their

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• alkenes under chiral BINOL-derived Brønsted acid catalysis has been studied by Houk and Rueping in 2014 [33]. These authors established the origin of the enantioselectivity and the differences between the catalyzed and uncatalyzed reactions, suggesting that the catalyzed reaction is, actually, a so-called

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• gave the corresponding epoxide 51 in low enantioselectivity and only 44% yield. The subsequent deprotection reaction led to compound 1 in 86% yield (Scheme 9). Besides the low enantioselectivity, the authors observed that the optical rotation value of the synthesized compound ([α]D +36.9, c 0.55, CHCl3

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• achieved. When AgOTf was replaced with silver (R)-BINOL phosphate, the asymmetric allylation proceeded in a moderate yield (60%) and enantioselectivity (40% ee). The structure of the ‘GaIOTf’ species was explored in more detail by Slattery, and a monovalent [GaI(18-crown-6)OTf] complex was isolated and

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• of each strategy, as well as the challenges remaining to be tackled. Keywords: enantioselectivity; grayananes; oxidation; 1,2-shift; total synthesis; Introduction The Ericaceae are a large plant family, with over 4250 known species all around the world [1]. While Ericaceae’s toxicity has been known

• structure of grayananes. Nevertheless, this approach is somehow lower yielding than the previous ones. Regarding enantioselectivity, both Newhouse’s and Luo’s syntheses rely on an enantioenriched precursor obtained in 86% ee. On the other hand, while Ding’s syntheses were performed in racemic form, the

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• electrophile and the nucleophile with the specific preorganization of the substrates by the catalyst is crucial for high enantioselectivity [67] (as in example A in Scheme 4). However, in example B the transition state without specific interactions between the sulfide and the catalyst is proposed. In this case

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• ]. Based on the fact that the cis-configuration between the sulfur and the pivalate was absolutely required for enantioselectivity, an interaction between both the sulfur and pivalate carbonyl oxygen with the hydrogen of Hantzsch ester's NH was proposed (Scheme 5). Thus, rather weak interactions might

• still be important in the assembly of a ternary complex and the enantioselectivity of the reaction. The evaluation of the catalysts is shown in Table 1. CPA 4 was completely ineffective at inducing chirality (Table 1, entry 1) and catalyst 2 was not much better (entry 2). Catalyst 3 on the other hand

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• tetraaminobisthiourea chiral macrocycles as catalysts in decarboxylative Mannich reactions. Low macrocycle loading was used to catalyze the decarboxylative addition of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. It was reported that effective activation