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

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• of the necessary variations to the nitro-Mannich/lactamisation cascade having been tested, optimised and scoped, we looked at the possibility of combining it with a catalytic asymmetric synthesis of a particular Michael adduct, so as to construct a one-pot enantio- and diastereoselective four

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky

• Guolei Zhao,
• Chao Yang,
• Bing Li and
• Wujiong Xia

Beilstein J. Org. Chem. 2011, 7, 1342–1346, doi:10.3762/bjoc.7.158

• chain was accomplished by the selective protection of the hydroxy groups and two-time implementation of the Wittig olefination reaction. Keywords: asymmetric synthesis; beetle; fatty acid amide; isolation; Introduction The leaf beetle Ambrostoma quadriimpressum Motschulsky (Coleoptera: Chrysomelidae

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• relative acidity of benzylic protons makes enantioselective deprotonation in the style of Scheme 1, of one of a pair of enantiotopic aromatic methyl, alkoxymethyl or acyloxymethyl substitutents, a viable approach to the asymmetric synthesis of atropisomeric molecules. We have developed a number of methods

• ], sulfides and sulfones [13], and many of the methods we developed for their asymmetric synthesis employed dynamic resolution techniques under kinetic or thermodynamic control [6][11][13][14][15][16]. The mechanistic possibilities associated with dynamic resolution were initially elaborated by Beak for

• enantiomeric enrichment in the product 5 [22]. In this paper we report parallel studies on the attempted asymmetric synthesis of atropisomeric diaryl ethers in diastereomerically and/or enantiomerically enriched form by the directed deprotonation and electrophilic quench of benzylic positions ortho to a

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• The discovery of new chiral ligands and auxiliaries continues to expand the frontiers of catalytic asymmetric synthesis. In particular, C2-symmetric diols, such as (S)-BINOL (1) [1] and (−)-TADDOL (2) [2] (Figure 1), have garnered considerable attention owing to the wide variety of asymmetric

• with the reported synthesis and should be effective for the rapid production of new ligands for asymmetric synthesis. Conclusion In conclusion, an efficient and economical process was developed for the direct functionalization of hydrobenzoin that relies on a directed ortho,ortho'-dimetalation strategy

• asymmetric synthesis and the tetralithio intermediate 8. Percentage of (R,R)-hydrobenzoin (3) (○), monodeuterohydrobenzoin (13) (■), and dideuterohydrobenzoin (9) (Δ) as determined by mass spectrometry (ESI) [23]. Percentage of methylhydrobenzoin (14) (■), and dimethylhydrobenzoin (15) (Δ) as determined by

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• product was established. Keywords: amino acid; asymmetric synthesis; conformational memory; isotopic label; isotopomer; quaternary stereogenic centre; Introduction In connection with our work on the control of conformation in helical foldamers [1][2][3] built from quaternary α-amino acids [4][5], we

• common component of several fungal and bacterial antibiotic metabolites [14], and the helix-forming properties of these metabolites, which encourage them to embed themselves into cell membranes, are at the origin of their biological activity. The methods available for the asymmetric synthesis of

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• , representative of the subject areas described above, demonstrates the current activity in aromatic chemistry. For example, the DoM reaction as applied to the construction of molecules of value for asymmetric synthesis is nicely presented by Rob Britton; lithiation chemistry in service of heterocyclic synthesis

Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene

• Alexandre Pradal,
• Chung-Meng Chao,
• Patrick Y. Toullec and
• Véronique Michelet

Beilstein J. Org. Chem. 2011, 7, 1021–1029, doi:10.3762/bjoc.7.116

• evaluated: The corresponding bicyclic adducts 4e and 4f were isolated in modest to good yield and 95% ee. Considering the observed highly stereoselective reactions of oxygen-tethered 1,6-enynes, we decided to study the challenging asymmetric synthesis of pentasubstituted cyclopropyl derivatives [67][68][69

• (99.9:0.1), flow rate 0.5 mL/min, λ = 215 nm): retention times 11.8 and 12.6 min, ee 73%; [α]D23 +11.7 (c 1, CHCl3). First reports on the racemic and asymmetric synthesis of bicyclo[4.1.0]heptenes. Synthesis of oxygen-tethered 1,6-enynes. Nitrogen-tethered 1,6-enynes. Synthesis of pentasubstituted

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

Alkene selenenylation: A comprehensive analysis of relative reactivities, stereochemistry and asymmetric induction, and their comparisons with sulfenylation

• Vadim A. Soloshonok and
• Donna J. Nelson

Beilstein J. Org. Chem. 2011, 7, 744–758, doi:10.3762/bjoc.7.85

• selenenylation; asymmetric synthesis; calculations; electronic effects; regioselectivity; relative reactivities; steric effects; Introduction Electrophilic addition to alkenes is one of the most fundamental, generalized, and versatile methods for selective functionalization of hydrocarbons [1]. Despite recent

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• /hydroboration/oxidation, which gave the best results when the Hoveyda–Grubbs catalyst 6 was used in the RCM (Scheme 15). Interestingly, in this case the asymmetric synthesis of the protected RCM precursor 78 started from a non-chiral source, the alcohol 75, and proceeded with complete stereocontrol over the 11

• promoted by the 1st-generation Grubbs catalyst 2 is starring again in the divergent, flexible methodology disclosed by Singh and Han [69] for the asymmetric synthesis of several deoxyiminocyclitols (1-deoxymannonojirimycin (63), 1-deoxyaltronojirimycin (65), 1-deoxygulonojirimycin (91), 1

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• medicinal chemistry, surprisingly few effective methods are suitable for the asymmetric synthesis of tertiary thiols. This review details the most practical of the methods available. Keywords: asymmetric synthesis; organolithium; sulfur; substitution; thiol; Introduction Organosulfur compounds play key

• , sulfimines and sulfilimines [9]. Chiral sulfoxides and sulfonium ylids have themselves been extensively used as tools for asymmetric synthesis [3]. With regard to chiral sulfur(II) compounds – namely thiols and thioethers (sulfides) with chirality at carbon – methods available for their asymmetric

• preparation are abundant, and usually rely on stereospecific substitution reactions [9]. These reactions are well suited to the construction of secondary thiol derivatives. By contrast, few methods are suitable for the asymmetric preparation of simple tertiary thiols 1. While the asymmetric synthesis of