A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. Keywords: asymmetric synthesis; hydration; natural products; terpenes; transannular epoxide opening

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• ; Introduction The high demand of enantiopure organic compounds in the fine chemical industry gives impetus to the development of chiral technologies. Among them, the catalytic asymmetric synthesis represents the state of the art in organic chemistry [1]. Over the past four decades, the asymmetric synthesis

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• ; m.p. 55 °C; [α]D20 +260 (c 0.37, CHCl3). Other analytical data of 1 were identical to those reported by our group previously [11]. Structure of ryanodine and the Diels–Alder reactions for construction of the potential intermediates of ryanodine. Asymmetric synthesis of 7 and determination of the

• effectively promoted by TBSOTf to produce a bicyclo[3.2.2]nonene derivative bearing two quaternary carbons. Seven additional transformations from the obtained bicycle delivered the C2-symmetric bicyclo[3.3.2]decene derivative, a key intermediate in our synthetic study of ryanodine. Keywords: asymmetric

• synthesis; C2-symmetry; catalysis; Diels–Alder reaction; Lewis acid; natural product; quaternary carbon; Introduction Ryanodine (Scheme 1) [1][2][3] is a potent modulator of the intracellular calcium release channels, known as ryanodine receptors [4][5]. Its complex architecture, including eight contiguous

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• reaction of chiral imines with enolates derived from Weinreb amides [13][14]. In previous work on the asymmetric synthesis of 2,6-disubstituted piperidines by C–N bond formation, we demonstrated that intramolecular aza-Michael ”type” cyclisation [15] using a β'-carbamate-α,β-unsaturated ketone

• devised for the asymmetric synthesis of β’-amino-protected-α,β enones, a valuable intermediate for the synthesis of trans 2,6-disubstituted piperidines. The scope and limitation of the aza-Michael reaction were studied with a range of substrates. We are currently working on the application of this

• = 15.9, 4.2 Hz, 1H), 2.71 (dd, J = 15.9, 6.5 Hz, 1H), 1.19 (d, J = 6.8 Hz, 3H), 1.14 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 198.8, 155.9, 143.4, 134.3, 130.6, 128.9, 128.4, 126.3, 60.6, 46.3, 44.1, 20.5, 14.6; HRMS-ESI (M + Na): calcd. for C15H19NO3Na 284.1263, found 284.1275. Asymmetric

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• barrier of the Diels–Alder reaction of 7a with 1,3-butadiene, involving its attack from the Si face, is lower. It is found that in this case, the exo approach of the diene is slightly preferred over the endo approach. Keywords: aluminium(O-menthoxy) dichloride; asymmetric synthesis; >C=P– functionality

• in asymmetric synthesis, which is one of the most attractive methods from the atom-economy point of view [1] for producing single enantiomers selectively. Over the past three decades, a variety of reactions allowing the formation of C–H, C–C, C–N, C–O and other bonds enantioselectively have been

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• the possibility of introducing further functionalization on the molecule by trapping the reactive organolithium intermediates with electrophiles. Keywords: alkenes; asymmetric synthesis; carbolithiation; carbometallation; enantioselectivity; lithium; Introduction The carbolithiation reaction has

• chiral ligands for lithium, thus opening new opportunities for their application in asymmetric synthesis. The naturally occurring alkaloid (−)-sparteine, which has been until recently inexpensive and commercially available, is the most widely used chiral ligand in enantioselective carbolithiation

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• : asymmetric synthesis; benzimidazole; host-directed; myxovirus; small molecule inhibitor; Introduction Myxoviruses are divided into two evolutionarily distinct yet related families: the orthomyxoviridae, which is composed largely of the influenza viruses, and the paramyxoviridae, which includes respiratory

• of the pure isomers for further pharmacokinetic and animal studies, we present here an asymmetric synthesis of 1 and its congeners with improved aqueous solubility and antiviral potency. Results and Discussion Design. We previously reported a series of compounds with antiviral activity against a

• )- (left, magenta) and (R)- (right, cyan) enantiomers of 1. L-Tartaric acid salt (18f-tartrate) and benzenesulfonic acid salt (18f-benzenesulfonate) of 18f. Synthesis of anilino nitrobenzene 7a. Preparation of morpholinyl-o-nitroanilines. Asymmetric synthesis of (R)- and (S)-isomers by using two different

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• of 2,2-dimethylchromene 45. Synthesis of 2,3-disubstituted chromene 47 by Stukan and co-workers. Ravichandrans synthesis of 3-substituted chromenes 52–55. Synthesis of 3-substituted chromene 58 coumarin 59 by Paye and co-workers. Govender and co-workers asymmetric synthesis of 2-phenylchromenes 62

• and 63. Asymmetric synthesis of 2-phenylchromene 62 by Li and co-workers. Acknowledgements We thank DAAD-NAPRECA for the scholarship (ZYD), the University of Botswana and the Royal Society of Chemistry for financial support.

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• amplified in recent times. In this regard, catalytic asymmetric synthesis involving the use of chiral organocatalysts has emerged as a powerful tool from the infancy to the maturity of asymmetric organocatalysis [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The use of organocatalysts for

• . Alkylation of imine Alkylation of glycine imine by using a chiral phase-transfer catalyst emerged as a very good strategy for the asymmetric synthesis of amino-acid derivatives [59][60][61]. Lamaty and co-workers prepared a series of glycine Schiff bases 22 in excellent yield (97–98%) in short reaction time

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• 264 62 21 Department of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium Department of Chemistry, University of Bergen, Allégt. 41, N-5007 Bergen, Norway 10.3762/bjoc.8.239 Abstract The asymmetric synthesis of new chiral γ-chloro-α,β-diaminocarboxylamide

• -diaminocarboxylamides was optimized, which resulted in Nα-deprotected syn-γ-chloro-α,β-diaminocarboxylamides, N-sulfinyl-β,γ-aziridino-α-aminocarboxylamide derivatives, a trans-imidazolidine, and an Nα,Nβ-deprotected syn-γ-chloro-α,β-diaminocarboxylamide. Keywords: asymmetric synthesis; diaminoacid derivatives

• chemistry and is continuously under development [1][2][3]. Recently, our research group elaborated the asymmetric synthesis of new chiral γ-chloro-α,β-diaminocarboxyl esters by highly diastereoselective Mannich-type reactions of N-(diphenylmethylene)glycine esters across a chiral α-chloro-N-p

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• properties (Scheme 3) [13]. Since the MCR results in racemates, we decided to investigate the applicability of a chiral auxiliary MCR approach for the asymmetric synthesis of viridic acid (1). The Ugi-4CR is not specifically prone to asymmetric induction, but at least some auxiliaries are known to result in

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• framework of our recently described methodology for applying a new generation of nucleophilic glycine equivalents [27][28][29][30][31][32] to a general asymmetric synthesis of α-amino acids [33][34][35][36][37][38]. In this manner, modular assembly of achiral C2-symmetric pentadentate ligands 12 was carried

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• diastereomer. In the case of an asymmetric synthesis, however, the initial diasteromeric ratio would be reflected in the enantiomeric ratio of the final products when the downstream epimerization step is taken into account; this is illustrated for the limiting case of high facial selectivity with respect to

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• -pyrazolines starting from α,β-unsaturated ketones and phenylhydrazine or N-tert-butyloxycarbonylhydrazine in the presence of a chiral Brønsted acid or a phase-transfer catalyst [70][71]. Compared with monosubstituted hydrazines in organocatalytic asymmetric synthesis, disubstituted hydrazines were also

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• -unsaturated ketones have also responded as Michael acceptors in the organocatalytic tandem Michael addition reaction towards the synthesis of tetrahydroxanthones. Córdova et al. [50], in 2007, reported the first organocatalytic asymmetric synthesis of tetrahydroxanthenones through the domino Michael–aldol

• pyrrolidine-triazole-based C2 symmetric organocatalysts XXVIIa was reported by Sankararaman et al. [61] for the asymmetric synthesis of nitrochromenes 30 (Scheme 15). The reaction gave poor enantioselectivities both in toluene (15% ee) and in DMF (24% ee). In 2010, Das et al. [62] reported an organocatalytic

• is anticipated to have hydrogen-bonding interactions with the nitro group. The subsequent Henry reaction with the aldehydes, followed by dehydration, generated 3-nitro-1,2-dihydroquinolines. Conclusion The advantage of organocatalysts in asymmetric synthesis has grown tremendously since its advent

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• findings include their use as fluoromethylation reagents, as fluorophores or as directing groups [16][17][18][19]. Two quality characteristics make them particularly attractive for asymmetric synthesis: 1) The stereogenic sulfur atom which is stable towards many reaction conditions, and 2) the ease of

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• non-asymmetric version of the reaction using pyrrolidine-TFA as catalyst in acetonitrile. High yields (67–98%) and moderate to good diastereoselectivities (59:41 to 80:20) were obtained for amine donors of different ring size [24]. After successfully performing the non-asymmetric synthesis of

• regenerated (Scheme 11). The following year, Akiyama and co-workers reported another organocatalytic asymmetric synthesis of tetrahydroquinolines using chiral phosphoric acid as the catalyst [25]. In this instance, benzylidene malonates were used as the hydride acceptor. Another important feature of this

• -(dialkylamino)cinnamaldehydes. Mechanism for aminocatalytic redox reaction of ortho-(dialkylamino)cinnamaldehydes. Asymmetric synthesis of tetrahydroquinolines having gem-methyl ester groups. Asymmetric synthesis of tetrahydroquinolines from chiral substrates 18. Organocatalytic biaryl synthesis by Kwong, Lei

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• Veera R. Arava Laxminarasimhulu Gorentla Pramod K. Dubey R&D Laboratory, Suven Life Sciences Ltd., Hyderabad, India Department of Chemistry, J. N. T. University, Hyderabad, India 10.3762/bjoc.8.158 Abstract A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R

• )-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described. Keywords: asymmetric synthesis; (R)-tert-butanesulfinamide; cinacalcet hydrochloride; naphthyl ethyl sulfinamide; regioselective N-alkylation; Introduction Cinacalcet hydrochloride

• ][16][17][18][19][20]. In our quest to utilize the chiral tert-butanesulfinamides in asymmetric syntheses of chiral amine APIs in an industrial setting [21][22][23], we report a novel asymmetric synthesis of 1 (Scheme 1) based on (R)-tert-butanesulfinamide (2), which was developed and extensively

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• catalytic synthesis of which was unprecedented. Keywords: 3,3-disubstituted oxindoles; Michael addition; organocatalysis; quaternary stereogenic center; unprotected 3-substituted oxindoles; Introduction The catalytic asymmetric synthesis of 3,3-disubstituted oxindoles has recently received great attention

• ][10], 3-aminooxindoles [11][12][13][14][15] and 3-quaternary oxindoles [16][17][18][19][20]. Despite achievements, the catalytic asymmetric synthesis of 3,3-diaryloxindoles has not been reported. This is possibly due to the challenge in the construction of such congested quaternary stereogenic centers

• following steps. Even if there is much potential for further improvement in the ee, this sequential reaction represented the first example of catalytic asymmetric synthesis of 3,3-diaryl oxindoles. Conclusion In summary, we have developed the first example of organocatalytic Michael addition of unprotected

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• ketones are an important class of building blocks for the synthesis of 1,3-amino alcohols [1][2], 1,3-amino acids [3] and other bioactive nature products [4][5][6]. Given their synthetic significance, methods for the asymmetric synthesis of β-amino ketones have been extensively investigated over the past

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• cinchona alkaloids for catalytic Diels–Alder reactions [23][24]. Introduced in this paper is a new fluorous cinchona alkaloid ester for flourination of β-ketoesters. It is part of our recent effort on the development of recyclable fluorous reagents and organocatalysts for asymmetric synthesis [25][26][27

• ]. Results and Discussion Cinchona alkaloids and their derivatives have been well-explored in asymmetric synthesis [28]. We envisioned that the introduction of a fluorous tag could facilitate the recycling of cinchona alkaloids. The synthesis of fluorous quinine ester C-1 was accomplished by the reaction of

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• and also as important structural elements. Pyridine scaffolds possess important antiviral [15], anti-inflammatory [16][17], anticonvulsant [18], antibacterial [19], and antitumor pharmacological activities [20][21]. Chiral macrocyclic ligands have found wide application in asymmetric synthesis and

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• Dieter Enders Jeanne Fronert Tom Bisschops Florian Boeck Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.8.123 Abstract The first organocatalytic asymmetric synthesis of smyrindiol, by using an (S)-proline catalyzed enantioselective

• reaction; asymmetric synthesis; organocatalysis; proline; smyrindiol; Introduction Furocoumarins are a group of compounds that are structurally derived from psoralen or angelicin (Figure 1) [1]. Naturally occurring furocoumarins are mainly found in plants of the Apiaceae and Rutaceae families [2] and are

• diastereoselectivity, with a slight preference (18% versus 15%) towards the anti-isomer xanthoarnol (Scheme 2).We now wish to present the first diastereo- and enantioselective, organocatalytic, asymmetric synthesis of smyrindiol. Results and Discussion Retrosynthetic analysis Previously the proline-catalyzed

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• information, not only in the field of asymmetric synthesis and catalysis, but also in materials science [19][20][21][22][23][24]. During the course of our ongoing efforts dealing with the use of binol-based synthons for the production of functional, oriented nanomaterials and chiroptical sensors [25][26][27

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• known protocols employing terpene units [62] and carbohydrate-derived auxiliaries [63][64] for the asymmetric synthesis of the 1,2-oxazine derivatives. More recently, the use of (–)-menthol as a chiral auxiliary was presented for the separation of diastereomeric 6H-1,2-oxazines [65][66]. Subsequent