(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

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• product synthesis The synthesis of natural products is considered a good test of the synthetic potential of a new reaction. The Shono-type oxidation has proved itself in the following syntheses. Hurvois and colleagues have reported an electrochemical asymmetric synthesis of (+)-myrtine (66) as shown in

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• ) was successfully achieved. In order to provide further insight into enzymatic kinetic resolution of (±)-3 enantiomers, and to show its potential as a method for asymmetric synthesis of enantiomerically pure pharmaceuticals 9 and 10, this part of our study was aimed for investigating the feasibility of

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• classical resolution [41], enzymatic resolution in conjunction with HPLC [42], or HPLC separation of derived peptides [43], preparative HPLC separation on a chiral phase column [44], asymmetric synthesis from chiral precursors [45][46] including the stereoselective alkylation of aromatic compounds with

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• addition was observed. Amino ester 11 was obtained as a single product and transformed to the corresponding amino acids 10A and 10D in good yields on the gram scale. Keywords: asymmetric synthesis; β-amino acid; chiral; Michael addition; monoterpene; Introduction In the past decade, cyclic β-amino acids

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• systems and their ability to form charge-transfer complexes [4][5][6][7]. Much attention is also being paid to the development of new functionalized [2.2]paracyclophanes that can be used in asymmetric synthesis [8], while the formation of new bridges, particularly functionalized ones, has been somewhat

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• products or bioactive molecules will be discussed [10]. Similar technologies to the ones discussed here without such applications and other uses of chiral phosphonamide reagents in asymmetric synthesis such as Denmark’s carbanion-accelerated Claisen rearrangements [11][12] have been reviewed elsewhere [13

• mGluR agonist DCG-IV (162) (Figure 9) as a potent anticonvulsant and neuroprotective agent [123] had sparked interest in more efficient routes for its synthesis. Pellicciari and Marinozzi developed an asymmetric synthesis of DCG-IV (162) based on Hanessian’s cyclopropanation protocol (Scheme 20) [57

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• first asymmetric Strecker reaction [4]. The first asymmetric synthesis of α-aminonitirles via a chiral catalyst [5]. A reaction model composed of Me-CH=O, HCN, NH3 and (H2O)10 for geometry optimizations to trace elementary processes. Broken lines stand for hydrogen bonds. Possible pathways for the

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• chemical structure for the first time. Results and Discussion Until now, there is only one publication about the total synthesis of analogues of trachycladines A and B. In 2005, Enders et al. reported the first asymmetric synthesis of 4′-epi-trachycladines A and B in 14 steps. They used 2,2-dimethyl-1,3

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• triol 16. To extend into hydrophobic chemical space around our PreQ0 analogues, we prepared two novel derivatives containing the unusual 3-arylcyclohexylamine chiral motif present in 21 and 22. Zhou et al. had reported an asymmetric synthesis leading to the cis-3-arylcyclohexanamines with reasonable

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• sesquiterpenyl subunit in heronapyrroles A–C provoked the hypothesis that there might exist other hitherto unidentified metabolites. On biosynthetic grounds a mono-tetrahydrofuran-diol named heronapyrrole D appeared a possible candidate. We here describe a short asymmetric synthesis of heronapyrrole D, its

• produce an alternative bis-epoxy intermediate 3 that can deliver a hitherto undetected mono-tetrahydrofuran heronapyrrole (e.g., heronapyrrole D, Scheme 1). To test this hypothesis we completed an asymmetric synthesis of the putative natural product heronapyrrole D, and used this material to probe

• Streptomyces sp. (CMB-M0423) cultivations to test whether heronapyrrole D is indeed a natural product. The asymmetric synthesis of heronapyrrole D commenced with enantiomerically pure diol 8 (Scheme 2) synthesized in five steps from commercially available TIPS-protected 3-bromopyrrole 7 [3]. This reaction

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• reduction of a prochiral ketone. The phosphoramidate (Scheme 32-iii) was the most efficient catalyst for these two reactions (ee: 95–98%, conversion 87–98%). In relation with asymmetric synthesis, the determination of the enantiomeric excess (ee) is usually achieved by different methodologies including