Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• affected by the electron density of the aromatic counterpart. Keywords: acrylic esters; asymmetric synthesis; biomass; conformational equilibrium; π-stacking interaction; Introduction Noncovalent interactions have demonstrated to have relevant importance in chemistry and biology [1][2][3][4]. Considering

• an element of stereocontrol in highly selective chemical transformations has been widely explored [9]. In this context, as part of our continuous interest in the development of new tools for asymmetric synthesis using levoglucosenone (a biomass-derived chiral enone) [10][11][12][13][14][15], we

• aromatic rings. This can be useful in several fields, such as supramolecular chemistry, biology and material science and, in particular, in the area of asymmetric synthesis for the rational design of new elements of stereocontrol. Intramolecular aryl–vinyl π-stacking interaction of a levoglucosenone

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• properties [5], enzyme inhibition [6], peptide mimetic function [7], and herbicidal properties [8]. Since the biological activity of α-aminophosphonate derivatives is dependent upon the chirality of the α-position to the phosphorus atom, asymmetric synthesis of α-aminophosphonates has received considerable

• -disubstituted oxindoles bearing a quaternary stereogenic center at the C3-position have been reported to be biologically active against a variety of targets [17][18][19]. Consequently, the asymmetric synthesis of 3,3-disubstituted oxindole derivatives has received significant research attention over the past

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• ; metal amide; Findings Catalytic asymmetric synthesis is an ideal method to prepare optically active compounds [1]. In this context, catalytic asymmetric carbon–carbon bond-forming reactions that can be used for the efficient construction of fundamental frameworks of complex chiral molecules such as

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -aminophosphonates 36 in good yields (Scheme 10). Some of the resulting α-aminophosphonates showed insecticidal activity against Plutella xylostella [36]. An asymmetric synthesis of heterocyclic α-aminophosphonates has been reported by Fadel et al. [37]. Their studies showed that the three-component reaction of N

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• -oxindoles while working on asymmetric synthesis of 3,3-disubstituted-2-oxindoles via a Pd-catalyzed (chiral N-heterocyclic carbene as ligands) intramolecular α-arylation of an amide [35][36][37]. For this 'intramolecular dehydrogenative coupling' (IDC) of Csp2-H and Csp3-H they used 2.2 equiv of CuCl2 and 5

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• last decades. Additionally, 3-hydroxyoxindoles as versatile precursors have also been used in the total synthesis of natural products and for constructing structurally novel scaffolds. In this review, we aim to provide an overview about the catalytic asymmetric synthesis of biologically important 3

• . Inspired by the biological potential and synthetic utility, metal- or organo-catalyzed asymmetric synthesis of chiral 3-hydroxyoxindoles have been highly pursued in the last decades. An excellent review by Chimni and co-workers summarized the catalytic strategies for the enantioselective synthesis of

• chiral 3-hydroxyoxindoles [13]. During the last three years, significant progress on the catalytic asymmetric synthesis of enantioenriched 3-hydroxyoxindoles has been observed. In this review, we aim to provide an update about the asymmetric synthesis of 3-hydroxyoxindoles, literatures from 2013 to 2016

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• addition, allylic amines serve as versatile structural building block units for the synthesis of various functionalized organic compounds, playing an important role as intermediates in asymmetric synthesis [2]. Furthermore, asymmetric allylic amines can be obtained in enantiomerically pure form from

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• , however, very few of them provide N-substituted derivatives directly [54]. In this context, 1H-imidazol-4(5H)-ones 1 have been recently introduced as novel nucleophilic α-amino acid equivalents for the catalytic and asymmetric synthesis of N-alkyl, N-aryl and N-allyl α,α-disubstituted amino acids [55

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• reaction. The catalyst 17c showed opposite enantioselectivity when compared to the catalysts 17a and 17b, with the S-enantiomer formed as the major product. In 1991, Doyle and coworkers published asymmetric synthesis of lactones from alkyl diazoacetates in high enantioselectivity by intramolecular rhodium

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• stereogenic carbon centers; Introduction Recently, chiral 3-substituted oxindoles have been attractive targets in asymmetric synthesis due to their abundance in the structures of numerous natural products and pharmaceutically active compounds [1]. In particular, the chiral 3-aminooxindoles containing a

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• [22] with 1,4-dithiane-2,5-diol. Based on all above considerations and prompted by our interest in asymmetric synthesis of functionalized tetrahydrothiophenes [14], we wondered whether we could use bifunctional organocatalysts to develop a diastereo- and enantioselective cascade sulfa-Michael

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• chiral centers; organocatalysis; six-membered ring; thiourea; urea; Introduction During the last 15 years, organocatalysis has flourished and has been established as one of the three major pillars of asymmetric synthesis [1][2][3]. Among the modes of activation of organic molecules that have been

• , organocatalyst 23. More specifically, the reaction is a catalytic asymmetric synthesis of 8-oxabicyclooctanes via an intermolecular [5 + 2] pyrylium cycloaddition (Scheme 9) [20]. This novel [5 + 2] cycloaddition describes the coupling of a pyrylium ylide 19 with dipolarophile 20, in order to give access to the

• -unsaturated aldehydes 108, affording the desired products 110 in moderate to good yields and good to excellent stereoselectivities (Scheme 35). Recently, Wang and co-workers disclosed an asymmetric synthesis of dihydrocoumarins 113 containing adjacent stereogenic centers, utilizing the cinchona-derived

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• for the asymmetric synthesis of functionalised cyclopentanones was disclosed in 2009 by Rovis. The chiral secondary amine 60 catalyzes the initial asymmetric Michael addition of an 1,3-diketone and an enal to afford a δ-ketoaldehyde 61. Subsequently, a cross-benzoin reaction of the latter promoted by

• 72 with the NHC precatalyst 73 alone, on the other hand, afforded isochromeno(4,3-c)isochromene derivatives 75 (Scheme 44) [61]. A one-pot multicatalytic reaction for the asymmetric synthesis of complex tetracyclic tetrahydrocarbazole derivatives from readily available precursors was described by

• –Michael cascade. Divergent catalytic dimerization of 2-formylcinnamates. One-pot, multicatalytic asymmetric synthesis of tetrahydrocarbazole derivatives. NHC-chiral secondary amine co-catalysis for the synthesis of complex spirocyclic scaffolds.

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• HCPN-59 can be used in an asymmetric cyclopropanation. The hydrocupreine and hydrocupreidine-based catalysts HCPN-65 and HCPD-67 demonstrate the potential for phase transfer catalyst derivatives of the 6’-OH cinchona alkaloids to be used in asymmetric synthesis. Jørgensen’s oxaziridination. Zhou’s α

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• addition, 7-azaisatins were also applied in asymmetric synthesis [18][19]. Therefore, with our continuing interest in the catalytic application of bifunctional β-ICD [20][21][22][23], herein we report the enantioselective MBH reaction of 7-azaisatins with maleimides. A series of 3-hydroxy-7-aza-2-oxindoles

Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes

• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 117–124, doi:10.3762/bjoc.12.13

• a key structural feature for the introduction of asymmetry in the NHC ring. Second, these H atoms might transform the corresponding NHCs in potentially efficient chiral NHCs in asymmetric synthesis [22]. Following with the latter recipe, protic NHCs (pNHCs) consist of the presence of a N-bound H

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• also been widely used as chiral ligands and auxiliaries in asymmetric synthesis [3]. Therefore, the development of a new aminooxygenation reaction is still highly attractive [4]. Most of the existing aminooxygenation reactions involve an intramolecular cyclization step [5][6][7][8][9][10][11][12][13

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• Yusuke Kobayashi Ryuta Kuramoto Yoshiji Takemoto Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan 10.3762/bjoc.11.285 Abstract The first catalytic asymmetric synthesis of the key intermediate for beraprost has been achieved through an

• ], although it was reported that each of the isomers have different activities [11]. In order to reduce the adverse effects while maintaining the pharmacological activities, an effective route for the asymmetric synthesis of 1 is highly sought after, and such methodologies should also lead to the expanded

• few asymmetric syntheses relying on the optical resolution of racemic intermediates [16][17][18][23]. Herein we report the first catalytic asymmetric synthesis of the key intermediate 2 through organocatalyzed-enantioselective intramolecular oxa-Michael reaction [24][25][26]. Results and Discussion

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• ., Shanghai 201203, China 10.3762/bjoc.11.283 Abstract A novel and practical asymmetric synthesis of dapoxetine hydrochloride by using the chiral auxiliary (S)-tert-butanesulfinamide was explored. The synthesis was concise, mild, and easy to perform. The overall yield and stereoselectivity were excellent

• . Keywords: asymmetric synthesis; dapoxetine hydrochloride; stereoselectivity; (S)-tert-butanesulfinamide; Introduction Premature ejaculation (PE) is the most frequent form of ejaculatory dysfunction with a distribution of 39% of the general male population [1][2]. Dapoxetine hydrochloride (1, (S)-(+)-N,N

• synthesis of this interesting drug has attracted great attention, especially asymmetric synthesis approaches. However, only a few methods have been reported for the synthesis of enantiopure dapoxetine hydrochloride. The earlier methods included chiral/enzymatic resolution [5], whereas the newer approaches

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• particularly promising for large scale applications. Keywords: asymmetric synthesis; Belliotti (S)-PD 172938; heterocycles; isoindolinones cascade reactions; phase transfer catalysts; Introduction Among the nitrogen heterocycles, the isoindolinone ring system is a favored scaffold, owing to the wide range of

• hypnotic/sedative activity has been investigated only for rac-4 [6][7]. In the last years, the development of the efficient, catalytic, asymmetric synthesis of 3-substituted isoindolinones became a research field of great interest among organic and medicinal chemists [9][10][11][12][13][14][15][16][17][18

• -cyanobenzaldehydes [29]. Then we decided to address the asymmetric synthesis of bioactive isoindolinones, identifying the chiral isoindolinone 9 as a very useful, key building block, as shown in Scheme 1. Results and Discussion Asymmetric cascade reaction of 2-cyanobenzaldehyde under phase-transfer conditions As

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated. Keywords: asymmetric synthesis; natural products; total synthesis; Xenia diterpenoids; xenicanes; Introduction Terpenoids are

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• substrates were suitable despite being insoluble in water. Keywords: carbon–boron bond formation; catalytic asymmetric synthesis; chiral copper(II) catalysis; β-hydroxy nitriles; Introduction In recent years, optically active organoboranes have attracted considerable attraction as versatile synthons for

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• , the cyclobutene ester was subjected to a ROM–RCM and CM protocol under conditions with catalyst 2 in the presence of 2-methylpropenol 57 to afford the required butenolide intermediate 58 in 57% yield (Scheme 9). An asymmetric synthesis of humulanolides is achieved by a RRM approach. In this context

• derivative 104 were obtained in a 22:78 ratio (Scheme 21). Aubé and co-workers [26] have accomplished the asymmetric synthesis of the dendrobatid alkaloid 251F by employing a RRM as the key step. The required building block 108a has been synthesized from enone 107 via a RRM protocol. When enone 107 was

• , 224, and 226 with high regioselectivity. The thermodynamic stability of the product is anticipated to play an important role in the observed regioselectivity of these transformations (Scheme 45). In the course of the asymmetric synthesis of (−)-isoschizogamine, a bicyclic lactone 230 has been

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• auxiliary was described by the Czarnocki group [7]. For the commercial manufacture of mianserin enantiomers both the above mentioned processes are rather unjustified economically and the most advantageous method could be the enantioselective synthesis. Considering our experience in asymmetric synthesis of