Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• , it was not until 2016 that the first asymmetric aza-Piancatelli reaction was described. To control the absolute stereochemistry of the aza-Piancatelli rearrangement, Rueping [35], Sun [36], and Patil [37] independently demonstrated that chiral phosphoric acids can be used as an enantioselectivity

• optimization of the reaction conditions was required to achieve high enantioselectivity and good yield, with small variations to the catalyst architecture or solvent having dramatic effects on enantioselectivity or yield. Because of these challenges and our group’s ongoing interest in further developing the

• reaction of the furylcarbinol to generate the oxocarbenium intermediate. Second, by analogy to asymmetric induction in aza-Piancatelli reactions with chiral phosphoric acids, where enantioselectivity has generally been achieved by strategically installing bulky groups on the hydrogen-bonding catalysts, we

Enantioselective Diels–Alder reaction of anthracene by chiral tritylium catalysis

• Qichao Zhang,
• Jian Lv and
• Sanzhong Luo

Beilstein J. Org. Chem. 2019, 15, 1304–1312, doi:10.3762/bjoc.15.129

• , the enantioselectivity was low in most cases. In addition, the synthetic efforts to access these chiral cations were generally non-trivial which limited their further development. Recently, we developed a chiral ion-pair strategy for asymmetric carbocation catalysis, with chiral trityl phosphate as

• cycloadduct 5a in excellent enantioselectivity (97% ee), however, with only 9% yield (Table 1, entry 1). Subsequent efforts to improve the activity by enhancing the dissociation efficiency of latent carbocation through heating or photolysis did not lead to any improvement. We next investigated whether the

• anthracene (3a) and β,γ-unsaturated α-ketoester 4a. When TP was first treated with metal Lewis acid (Scheme 2a, and Table S1 in Supporting Information File 1), the reaction showed good reactivity but no enantioselectivity at all, indicating a strong background reaction (Table 1, entry 2). We next examined

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

• nitroalkenes in the presence of Ni(II) complexes with various chiral vicinal diamines was studied. This reaction provides convenient access to non-racemic 4-nitro-2-sulfonylbutan-1-ones with two stereocenters with high yield and excellent enantioselectivity (up to 99%). It has been established that the

• , which allows to obtain chiral cyclic sulfones with high enantioselectivity [10][11][12]. Also non-racemic cyclic sulfones can be obtained by the Diels–Alder reaction, catalyzed by chiral Lewis acids or organocatalysts. Rh- and Cu-catalyzed CH-insertion reactions occurring at moderate or high

• enantioselectivity are also known [13][14][15][16][17][18]. The studied methods for obtaining acyclic sulfones with stereogenic centers in the side chain are more limited. One of the most significant approaches to obtaining both cyclic and acyclic chiral sulfones is asymmetric hydrogenation in the presence of

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

• polyfurfuryl alcohol-supported catalysts for applications in heterogeneous enamine catalysis. The utilization of the polymer-supported catalysts in both batch and continuous-flow organocatalytic procedures proved moderate catalytic efficacy and enantioselectivity, but excellent diastereoselectivity in the

• diastereoselectivity remains constantly high in all solvents [19]. Unfortunately, the enantioselectivity of the Michael additions remained moderate with both catalysts in all tested solvents and conditions, only rising to 84% ee when using catalyst 3 in toluene. The reason of the better catalytic performance of PFA

• material by β-nitrostyrene (50 times as residence time calculated) limits the formation of the Michael product and, consequently, lowers the chemical efficiency. Despite the good level of diastereocontrol in Michael addition (dr 95:5 syn/anti), a little drop in the enantioselectivity was observed (i.e., 74

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• rearrangement that would lead to isoindolinone 46 through the bridged intermediate 51. Therefore, this mechanistic path shows that the enantioselectivity of the reaction is a consequence of a dynamic kinetic resolution of enamine 50. Cyanide can also be used, instead of isocyanide, in an analogous three

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• described in the literature [38][39][40], the authors recognized the importance of protecting the amide fragment of isatin, since it affects the reactivity and, in some cases, the enantioselectivity of processes. In order to prevent undesirable side reactions in the future, three-component condensations

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• , different from the synthesis of catalyst 3, asymmetric reduction of the corresponding ketone, (2-bromophenyl)(mesityl)methanone c, using (S)-(–)-2-methyl-CBS-oxazaborolidine as the catalyst resulted in a very low enantioselectivity (<15% ee) of the product, (2-bromophenyl)(mesityl)methanol (d, Scheme 3

• removing the chiral-resolving menthyl substituent with lithium aluminium hydride (LAH), the enantioselectivity of (R)-d was higher than 99% ee when checked with HPLC (Supporting Information File 1, Figure S3). Catalyst 4 was then obtained by homo-coupling of (R)-d with Ni(PPh3)3Br2/Zn with 37% yield. The

• previously to have a significant effect on controlling catalytic enantioselectivites [41][42]. For organocatalyst 6, it gave the highest enantioselectivity (59% ee) but a low chemical yield. When the bulkier trimethylacetaldehyde was used as substrate, the enantioselectivities were improved when 1–3 were

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

• improve the rate and modulate the regioselectivity and enantioselectivity of reactions [11]. For example, metal-based CD catalytic systems and CD derivatives for organocatalysis have already shown promising results in the studies by Hapiot and Monflier [12], Armspach [13] and others [14][15]. The chemical

• 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

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