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

• facial selection by the catalyst is required: (i) regioselectivity when R1 is different to H and enantioselectivity when R1 is equal to H (left or right) and (ii) diastereotopic face selection (top or bottom) as described in Scheme 2. Since the pioneering addition of a carbon–metal bond (carbometalation

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

• vinyl acetate in diisopropyl ether (DIP) was attempted. However, the yield and enantioselectivity of the desired alcohol (S)-4 were very poor (Table 1, entry 1). Also the acetylation of (±)-4 with vinyl acetate in diisopropyl ether using Candida rugosa lipase (CRL) and Pseudomonas fluorescens lipase

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• crucial for the intramolecular cyclopropanation reaction in a water/ether biphasic medium. The water-soluble catalyst could be reused at least six times with little loss in yield and enantioselectivity. Keywords: asymmetric synthesis; carbene transfer; cyclopropanation; diazoester; intramolecular

• diazoacetate could be cyclopropanated affording the corresponding lactone with low yield and good enantioselectivity (Table 1, entry 1). In case of the diazo compound derived from cinnamyl diazoacetate the corresponding lactone was obtained in high yield with high enantioselectivity (Table 1, entry 2). A

• spirocyclopropanation product and a functionalized cyclopropane were obtained with high enantioselectivities (Table 1, entries 3 and 4). N-Benzyl-diazoacetamide underwent the asymmetric cyclopropanation reaction affording the corresponding lactam in moderate yield and moderate enantioselectivity (Table 1, entry 5

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• excellent enantioselectivity (Scheme 36) [116]. This transformation merged a stereocontrolled radical pattern with a classical ionic process in a cascade sequence. In 2018, Orellana et al. developed the Ag(II)-catalyzed ring-opening and functionalization of cyclopropanols 91 with electron-poor aromatic

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

• excess starting from a commercial substrate. The reaction was carried out by using different commercially available immobilized enzymes, evaluating the catalytic activity and the enantioselectivity under different experimental conditions. Re-use of the most efficient enzyme was performed both in batch

• commercial free form or isolated from bacterial sources, both in kinetic resolution starting from the corresponding racemic amine and in asymmetric synthesis starting from the corresponding ketone. The first method, although it proceeds with high enantioselectivity, is a kinetic resolution and as a

• described [25]. However, the enzyme used in this study is not commercially available and no enantioselectivity of the reaction has been reported. Herein, we describe the use of several immobilized ω-transaminases in the asymmetric transamination of the selected substrate 1-Boc-3-piperidone. Selected

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

• reported on the first example of a helically chiral Hoveyda-type metathesis complex. This catalyst, bearing a mesityl and a helicene as the aryl groups, was preliminary examined in some model asymmetric metathesis transformations and showed promising levels of enantioselectivity. Further studies on the

• with the more encumbered and electron-donating 1,2-di-tert-butyl units was made with the hope to enhance reactivity and enantioselectivity in Grubbs-type olefin metathesis catalysts. Moreover, in order to reduce the whole ligand’s bulkiness which could have hampered attempts to prepare the catalyst

• [55] (Table 6). The size of the ring formed was found to have a crucial influence on the enantioselectivity of the reaction with the enantiomeric excesses decreasing when passing from five to six and seven-membered rings (Table 6, entries 1, 4 and 7). The use of halide additives such as NaBr and NaI

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• beneficial chelation effect was observed by Buchwald [28][29]. The origin of the enantioselectivity during the selectivity-determining step of the coupling of tolylboronic acid with naphthylphosphonate bromide was proposed by additional O-chelation. Previously, we also observed additional N-chelation during

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• the presence of Co(acac)3 and phosphoramidite ligand L afforded alkylated products 33 in high yields and enantioselectivity. A wide range of indoles and styrenes were well tolerated to form the corresponding alkyl products 33 in a branched selective manner. In addition to the directing group

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• enantioselectivity [1][2]. Probably the most effective approach in stereoselective synthesis is enantioselective catalysis, because cheap prochiral starting materials can be converted into chiral enantiopure products and no undesirable side products are formed [3][4]. Therefore, the development of new ligands is

• of tested solvents. Promising enantiomeric ratios ranging from 76:24 to 84:16 were obtained. For the tested solvents it seems that the solvent just has a small influence on the enantioselectivity. Interestingly, in diethyl ether 5b showed the smallest excess of (R)-16 (entry 3, Table 3) whereas 5i

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• reactions in aqueous solution with excellent enantioselectivity [35]. As part of our ongoing studies to develop novel types of organocatalysts for asymmetric catalysis, in this study, we aimed to synthesize novel upper rim-functionalized calix[4]thiourea cyclohexanediamine derivatives to catalyze asymmetric

• economy. Next, the effect of solvents on the reaction catalyzed by 2 was investigated and the results are summarized in Table 1. The results revealed that both the yield and the enantioselectivity were highly dependent on the solvents. Poor yields, lower enantioselectivities and long reaction time (48 h

• ) were observed when the reactions were performed in organic solvents or without any solvent (Table 1, entries 6–14). Interestingly, using toluene as the solvent afforded a higher enantioselectivity (90% ee) with a low yield (62%, Table 1, entry 5), while H2O as the solvent gave higher yields (99% yield

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• afford the diacetoxylation products in moderate yields and enantioselectivity when using Selectfluor as a terminal oxidant (Scheme 6). Diamination of alkenes The diamination of alkenes is attractive due to the significance of diamino moieties in diverse fields of the biomedicinal and pharmaceutical

• ratio of amines and HF was important for obtaining reasonable yields. Indeed, excellent 19F NMR yields albeit lower isolated yields were obtained in this reaction (Scheme 12). In an attempt to induce enantioselectivity, the chiral aryl iodide derivative 39 only gave a moderate enantioselectivity (22% ee

• , the cinnamamide 41i could be transformed to the corresponding difluorination product 42i with excellent enantioselectivity and high stereoselectivity, albeit in moderate yields (Scheme 14, top) [64]. Inspired by the propensity for such anchimeric assistance in these reactions, an enantio- and

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

• retarded the reaction due to their tight coordination to the catalyst whilst non-polar solvents such as cyclohexane resulted in poor enantioselectivity probably due to coordination of the product β-hydroxy sulfide. The protocol was, however, limited to unsubstituted cyclohexene oxide, and as its greatest

• -oxazaborolidine-catalyzed asymmetric borane reduction of β-keto sulfides 68 for the synthesis of β-hydroxy sulfides with high enantiomeric purity (Scheme 20) [54][55]. The enantioselectivity was highly dependent on the nature and bulkiness of the substituents on both ends of the carbonyl group. While the

• reduction of aromatic β-keto sulfides provided excellent enantioselectivity, the reduction of the corresponding alkyl β-keto sulfides gave low enantioselectivity. Ruano and co-workers reported the asymmetric synthesis of β-hydroxy sulfides via connectivity of a suitably substituted benzylic carbanion with

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• product 5a in 86% yield up to 35% ee (Scheme 4). In order to assess the effect of the calixarene backbone on the catalytic activity and enantioselectivity, they also performed the reaction in the presence of a chiral monoamide and an achiral calix[4]arene-tetramide. The results obtained in the presence of

• the Henry (nitroaldol) reaction between 4-nitrobenzaldehyde (21) and nitromethane (22, Scheme 6). Excellent yields (up to 99%) were obtained in CH3CN and THF when H2O was added. The best enantioselectivity (7.5%) was achieved in a mixed protic solvent (EtOH/H2O, 3:1, v/v) with a yield of 54% when 5

• asymmetric Tsuji–Trost allylic alkylation of 1,3-diphenylprop-2-enyl acetate (33) with dimethyl malonate (34, Scheme 9). Both, good catalytic activity and enantioselectivity (ee values up to 86%) were obtained with the potassium cation. This was due to the more strongly interaction of the dimethyl malonate

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• high yields (89–99%) and enantioselectivities (92–99% ee). A lower yield (78%) albeit combined with a high enantioselectivity (94% ee) was obtained in the reaction of a dihalogenated isatin imine (R1 = 4,7-Cl2). The scope of the process was also extended to 1,3-dicarbonyl compounds other than

• symmetrical pentane-2,4-dione, such as 1,3-diphenylpropane-1,3-dione (R2 = R3 = Ph), that also led by reaction with the unsubstituted isatin imine (R1 = H) to the corresponding product in high yield (93%) and enantioselectivity (96% ee). Furthermore, unsymmetrical 1,3-dicarbonyl compounds, such as methyl

• good yields (42–81%), low to moderate diastereoselectivities (4–44% de), and low to excellent enantioselectivities (15–96% ee) for the major diastereomers formed (Scheme 4). In general, most of the isatin imines underwent the reaction smoothly with a good level of enantioselectivity (88–96% ee) and

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• enantioselectivity [24]. Later, Kita et al. used chiral tartaric acid derivatives to synthesize chiral I(V) reagents 2 from PhIO2. This represented the first example of the catalytic use of chiral hypervalent reagents in the oxidation of sulfides to sulfoxides with decent enantioselectivities (ees, Scheme 2a). The

• sulfides to sulfoxides with good yields but with poor enantioselectivity (Scheme 2b) [27]. Later, Zhdankin et al. synthesized different classes of chiral I(V) reagents 4 based on various amino acids as sources of chirality. The oxidation of the readily available 2-iodobenzamides (synthesized from amino

• with excellent enantioselectivity (Scheme 2d). Another class of chiral I(V) reagents 6 was synthesized by Wirth et al. who synthesized the desired compounds through esterification between chiral alcohols and the I(I)-substituted aromatic acids followed by oxidation with dimethyldioxirane (Scheme 2e

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• performing catalytic reactions with high enantioselectivity and efficiency [13][14]. As a result, a wide range of chiral catalysts have been established [15][16]. Chiral catalysts are, however, not only incompatible with aqueous solutions, but also expensive due to the structural complexity of the ligands

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• are utilised. The employment of a variety of different ligands such as phosphines, amines and carbenes allows precise tuning of the properties of homogeneous Pd catalysts, which led to significant improvements in turn over number (TON), reaction rates, enantioselectivity as well as catalyst robustness

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

• ) groups in good-to-high yields and enantioselectivities. Axial backbones and substituents on phosphorus atoms of chiral phosphine ligands critically influence the enantioselectivity. Moreover, the methylation of simple perfluoroalkylated ketones is found to be facilitated by only chiral phosphines without

• have so far been reported [7][28][29][30]. In 2007, Gosselin and Britton et al. reported that treatment of ethyl trifluoropyruvate (1a) with (R)-BINOL-mediated organozincate as a chiral methylating regent provided the corresponding methylated tertiary alcohol 2a in moderate enantioselectivity (Scheme 1

• , reaction 1) [31]. Kinetic resolution of racemic α-trifluoromethylated tertiary alcohols 2a by an enzyme is also reported to give the corresponding alcohols 2a in high enantioselectivity (Scheme 1, reaction 2) [32]. However, there has been no report for catalytic asymmetric methylation of trifluoropyruvate

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• successfully developed a rhodium-catalyzed asymmetric arylation process leading to triarylmethanes 25. With the application of mild reaction conditions (40 °C, 15 h), a high enantioselectivity (≥90% ee) was reached with good to excellent yields. (Scheme 2). Starting from 2-naphthol, 2,2-disubstituted 3

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• yet sufficiently understood, if properties like solvent or temperature stability need to be optimized, or regio-, chemo- or enantioselectivity and substrate specificity shall be changed. Thus, the optimization and variation of proteins, in particular of enzymes, by random mutagenesis and subsequent

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• based on the use of chiral substrates and enantioselective catalytic procedures. Keywords: asymmetric (aza)-Reformatsky reaction; asymmetric synthesis; chirality; diastereoselectivity; enantioselectivity; total synthesis; Introduction The Reformatsky reaction involves the formation of β

• alcohols and BINOL (1,1’-bi-2-naphthol) derivatives, ligand 53 was selected as optimal ligand when used at a stoichiometric amount in THF at −40 °C. As shown in Scheme 21, the corresponding fluorinated chiral β-amino alcohol 54 was formed in both moderate yield (60%) and enantioselectivity (37% ee

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

• bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of meso-cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of (S

• development of chiral bifunctional urea 1 [35], thiourea 2 and 3 [36][37], sulfonamide 4 [38][39][40] and squaramide 5 [38][39][40] catalysts derived from chloramphenicol base (Figure 1), which showed excellent reactivity and enantioselectivity for this asymmetric transformation. A typical example of the

• decreased the reactivity and enantioselectivity and required diluted concentrations with low temperatures [47]. With the new chloramphenicol base amide organocatalysts we envisioned that the presence of a bulky oxygen group could avoid the intermolecular aggregation of the catalyst, while keeping the

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

•  2, entries 3–5). By employing catalyst 9b, the reaction proceeded at −60 °C to give phthalide 1a in 51% yield with 12% ee (Table 2, entry 4). To improve the enantioselectivity of the present nucleophilic trifluorometylation/lactonization, we surveyed suitable conditions for the catalytic asymmetric

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• . These methods have often the drawback of generating mixtures of regioisomers. Future efforts will be focus on developing efficient and less expensive reagents, along with a better understanding of mechanisms, improving the regioselectivity and enantioselectivity in these trifluoromethylation processes

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• , followed by the intramolecular Wittig reaction gave the corresponding 3,6-dihydropyran derivatives 44 in yields of 34–56% and a high enantioselectivity of 95–98% (Scheme 30) [43]. Pyran derivatives are structural elements of many natural biologically active compounds [44][45][46][47]. 2.2.2. Reactions with