Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• catalyst worked well for various (Z)-isomer substrates. Opposite enantiomers were obtained from (Z)- and (E)-isomers, with a higher enantiomeric excess from the (Z)-isomer. Keywords: catalyst; chiral NHC; conjugate reduction; copper catalysis; enantioselective reaction; Introduction Since the leading

• ligand on the copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with hydrosilanes, placing a focus on (Z)-isomer substrates, which generally gave slightly lower enantiomeric excess with the chiral bisphosphines compared to the (E)-isomer substrates. Results and Discussion

[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

• 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

• pseudorotation. This, in turn, should have led to a remarkable deterioration of the enantiomeric excess of the product. The same might be postulated for the rearrangement of alkenylphosphine sulfide 65, which should form a pentavalent intermediate equally well. In the next step, the enantiomerically enriched β

• 67, and S-acylated γ-mercaptoalkylphosphine oxide 68. Compound 66 was obtained with complete stereoselectivity, whereas the enantiomeric excess of both 67 and 68 was higher, 78% ee and 76% ee, respectively. The phosphine sulfides (SP)-19 and (SP)-20 underwent rearrangement to the corresponding chiral

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

• cathode in an undivided cell in the presence of cinchonidine alkaloid as the source of chirality [30]. They modified the electrolysis conditions using a mixture of CH3CN/H2O and tetraethylammonium iodide as the supporting electrolyte and achieved a slight improvement in the enantiomeric excess (Scheme 7

• of 38 to the corresponding sulfoxide 39 with excellent chemical yield although the value of enantiomeric excess was considerably low (Scheme 16) [46]. A few years later, Komori and Nonaka, in two consecutive reports, established a modified method for the asymmetric electrochemical oxidation of alkyl

• aryl sulfides 40 to their corresponding sulfoxides 41 using poly(amino acid)-coated platinum electrodes with moderate yield and good to excellent enantiomeric excess (Scheme 17) [47][48]. Osa and co-workers, in 1994, made an important contribution in the area by developing an enantioselective method

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• a palladium catalyst (Scheme 9). Under these conditions, the fluorination of ethyl 2-cyano-2-phenylacetate afforded the product with highest enantiomeric excess (93%). In 2013, Kim’s group [46] described an enantioselective electrophilic fluorination of α-chloro-β-keto phosphonates with up to 95% ee

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• degassed by the freeze-pump-thaw method, the catalysis was performed under inert gas conditions (Argon), and the chemical conversions and yields were determined by 1H NMR spectroscopy (see Supporting Information File 1). The enantiomeric excess of the product 14 was determined after conversion with (2S,4S

• )-(+)-pentanediol into diastereomers and by integration of the corresponding signals in the 1H NMR spectrum. In all experiments with NDI 1 the enantiomeric excess exceeded a value of 78%; in all experiments with cNDI 6 the enantiomeric excess was higher than 81%. This parameter is omitted for clarity in the

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• significantly more slowly to the sulfone. When the substrate was (p-OMe)PhSCF2CH3, then the resultant (demethylated) phenol sulfoxide had an enantiomeric excess of 60%, and when the substrate was the β-substituted-SCF2CH3 naphthalene, then the enantiomeric excess of the resultant sulfoxide was 54%. There was no

• we could not determine the absolute stereochemistry of the predominant enantiomer, it was clear from the assay that there was a significant enantiomeric ratio (4:1) of 6 which translates to a 60% enantiomeric excess (ee, see Supporting Information File 1). We note that there have been chemical

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

• phase (Figure 1). This simple procedure was successfully used for the semi-preparative separation of 156 mg of (rac)-1. It was possible to separate more than 25 mg substance per injection giving both enantiomers of 1 in an enantiomeric excess of >99%. Electronic circular dichroism spectra (ECD) were

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• chromatography on silica gel using n-hexane/EtOAc as eluent. Enantiomeric excess (ee) was determined by chiral HPLC analysis through comparison with the authentic racemic material. Assignment of the stereoisomers was performed by comparison with literature data. Synthesis and characterization Prolyl pseudo

• flash column chromatography (EtOAc/hexane 1:9, v/v). The spectroscopic data are in agreement with the published data [15]. The enantiomeric excess was determined by chiral-stationary phase HPLC (Chiralpak OD-H, hexane/iPrOH 99:1, v/v, 25 °C) at 1.00 mL/min, UV detection at 210 nm: tR: (syn, major

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• of GPP and GGPP, respectively. Compounds known to also originate from non-enzymatic hydrolysis are labelled with an asterisk. The enantiomeric excess values were determined based on GC analysis on a chiral phase. EI mass spectrum of 1 arising from an incubation of (2-2H)GPP and IPP with FPPS and HcS

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• evaluated in several enantioselective reactions, specifically in the asymmetric allylic amination (AAA), which showed a promising enantiomeric excess of up to 75% ee. Furthermore, a new disubstituted α-CD catalyst was prepared as a pure AD regioisomer and also tested in the AAA. Our results indicate that (i

• lower enantiomeric excess (54% ee). Conversely, Shen et al. [18] performed an aldol reaction in a buffer using L- and D-proline-derived CDs connected through a pyrrolidine skeleton as catalysts and observed 94% ee. More recently, Liu et al. [19] reported the excellent enantioselectivity of 99% ee in an

• alkaloids have never been prepared and tested in asymmetric organocatalysis. Thus, in this study, we investigated methods for attaching cinchona alkaloids to CD skeletons, and we assessed the enantiomeric excess of the resulting CD derivatives as organocatalysts in asymmetric reactions, specifically in the

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• epoxides, for which the maximum theoretical yield of the reaction is 50%. Here, however, the yield of the sn-1,3-protected monoacylglycerol was high, and consequently we expected the enantiomeric excess of the product to be low. This, assumption was confirmed by analysis of the sample by high-performance

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• bearing two adjacent quaternary stereogenic centers in a single pot operation. The simple preparation of enantiomerically enriched cyclopropene afforded the corresponding cyclopropanols in high enantiomeric excess. This transformation was then applied to unfunctionalized diversely substituted

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• chicken liver esterase proceeded with modest enantioselectivity [41][42]. Rhizopus arrhizus-mediated hydrolysis of the acetate furnished the enantiomerically pure alcohol (99% ee), however, the enantiomeric excess (ee) of the antipode acetate was very poor (5–9%) [43]. On the other hand, the Amano PS

• absolute configurations of (R)-5 and (S)-4 were assigned by comparison of the chiroptical data with those reported [45]. The stereochemical outcome of the reaction is consistent with Kazlauskas’ empirical rule [51]. The conversion (% c) and the enantiomeric excess (E) values were calculated according to

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• dichloromethane (DCM) and 1,2-dichloroethane (1,2-DCE) the reaction takes place but without any enantiomeric excess (ee) (Table 7, entries 2 and 3). In DCM the highest yield is isolated, but that is due to a fast background reaction [45]. With toluene as solvent, no background reaction is observed (Table 9, entry

• 9). To stabilize and improve the ion pair, polar solvents are tested as diethyl ether and dimethylformamide gave no conversion and starting material is obtained (Table 7, entries 4 and 5), acetonitrile and acetone increase the yield (Table 7, entries 6 and 7), but without any enantiomeric excess. In

• the yields and the enantiomeric excess. In a third reaction, the 1,4 addition of silyl keten acetals 11 to chromone 20 is investigated (Table 11, Scheme 8). Chromone 20 is first transformed to the oxonium ion pair 21. Catalyst BIFOXSi(OH)2 (9) binds the triflate anion via hydrogen bonding and leaves

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• and in a semi-continuous system. The selected biocatalyst showed good stability under the reaction conditions providing consistent results in terms of conversion and enantiomeric excess after several cycles. The reported results may be of practical interest in view of the development of this

• enantioselectivity (>99%) but longer reaction times were required to achieve high yields of up to 94% (Table 1, entries 6, 7, and 8). It should be noted that the TAs-IMB enzymes showed excellent enantioselectivities as demonstrated by the enantiomeric excess values which were all above 98%. Therefore, these results

• represent an improvement in the preparation of enantiomerically pure 2 compared with literature data [23]. Höhne et al. obtained only the (R)-enantiomer in 42% yield and 97% ee as a result of kinetic resolution of 1 using ω-transaminase and pyruvate as an amine acceptor. The enantiomeric excess in entries 9

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

• use of any halide additive. The unsymmetrical NHC catalysts 164, 173 and 174 were also examined in the asymmetric synthesis of [7]helicene (180). Among them, complex 174 exhibited the highest degree of selectivity, leading to the desired product with an enantiomeric excess of 80% [56]. An extension of

Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes

• Yo Hiranoi and
• Koji Nakano

Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255

• stereochemistry of the copolymer prepared from enantiomerically pure (S)-PO. Because a ring opening at the methine carbon results in both a regioerror and the inversion of stereochemistry at the stereocenter, the enantiomeric excess (ee) of the repeating unit in the copolymer should reflect the regioregularity

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• performed in neat TFA for 5 min, the keto amides 5c–f were obtained in poor enantiomeric excess and the concomitantly formed pyrrolinones 6c–f were fully racemic. This again is in sharp contrast to analogues 9, which cyclise to 10 with excellent retention of configuration [34]. Higher enantiomeric ratios

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• . The reaction products 39 were isolated in good yields with more than 78% enantiomeric excess (Scheme 10). The active catalytic hypervalent iodine species was generated in situ by oxidation of optically active iodoarene 38 using mCPBA as an oxidant. 2.4. Application of spirolactones in natural products

• β-substituted 3-(methoxyphenyl)-N-methoxypropionamides 46 with [bis(trifluoroacetoxy)iodo]benzene (PIFA, 31) in dichloromethane (Scheme 14). The reactions were carried out at low temperature and spirolactams 47 were achieved in high yields with up to 96% enantiomeric excess. Furthermore, these

• oxidation of the chiral C2-symmetric iodoarene 85 that was playing the key role for the oxidative spirocyclization of phenols. In addition, N-methyl-N-(2-naphthyl)-2-naphthamides 87 were also cyclized to corresponding spiro compounds 88 in high yields and with upto 84% enantiomeric excess (Scheme 31

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• derivative was employed for the asymmetric dioxytosylation of styrene and its derivatives. The electrophilic addition of the hypervalent iodine(III) compound toward styrene proceeded with high enantioface selectivity to give 1-aryl-1,2-di(tosyloxy)ethane with an enantiomeric excess of 70–96% of the (S

• . [15][16][17] reported the dioxytosylation of styrene (1a, Scheme 1). Chiral hypervalent iodine reagents 2 bearing a 1-methoxyethyl side chain were used for enantiocontrol of the dioxytosylation, and the maximum enantiomeric excess (ee) of the product 3a reached 65%. Despite recent rapid progress in

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• under reduced pressure. The residue was purified by silica gel column chromatography to give p-nitrobenzoylated alcohol 2’. The enantiomeric excess was determined by chiral HPLC analysis. (S)-3-Ethoxy-1,1,1-trifluoro-2-methyl-3-oxopropan-2-yl 4-nitrobenzoate (2a’) The yield of alcohol 2a (86%) was

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• preparation of β-amino acids, especially protocols leading to products with high enantiomeric excess (ee), which are required to test the pharmacological activity of each enantiomer [11][12][13]. In this regard, several methods for the asymmetric synthesis of β-amino acids have been documented [14][15][16][17

• 2M2B was replaced with other LAG additives a lower yield was observed (Table 1, entries 4–6). Nevertheless, the enantioselectivity of the process is maintained (95% ee), except when hexane was used (Table 1, entry 7), where a higher yield was observed (60%) although with a lower enantiomeric excess (86

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• derivatives with good enantiomeric excess (ee) values, respectively. However, the utility of the reaction is limited to α,β-unsaturated aldehydes with aromatic/alkane substitutions and nitroolefins with aromatic substitutions. Additionally, Shao’s group (Scheme 1, reaction 1C) developed a one-pot thiourea

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• organocatalysts with the privileged pyrrolidine motif. When used in the asymmetric Michael addition of aldehydes to nitroolefins, diastereoselectivities of up to 93:7 and enantioselectivities of up to 85% enantiomeric excess for the syn-adduct were obtained in the presence of the most effective organocatalyst OC4

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• process. The stereochemistry of the adduct can be simply switched to the opposite enantiomer, by using the enantiomeric supported catalyst PS–(R)-pybox–calcium chloride. The enantiomeric excess of the products was about 96%. Two more steps consisting in a Pd-catalyzed hydrogenation reaction and a