An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• is achieved via an asymmetric addition of phenylethylzinc to the imine N-oxide 2.66 yielding the corresponding 3,4-dihydroisoquinoline-N-hydroxide 2.68. Further reductive cleavage of the hydroxylamine moiety followed by activation with 4-nitrophenyl chloroformate [79] yields the intermediate 2.69. In

Metal-mediated aminocatalysis provides mild conditions: Enantioselective Michael addition mediated by primary amino catalysts and alkali-metal ions

• Matthias Leven,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2013, 9, 155–165, doi:10.3762/bjoc.9.18

• direct aldol reaction, which is mediated by copper ions and amino acid derivatives [14] or enamine nucleophilic addition to palladium π-allyl electrophiles [15][16][17]. We report the development of new catalysts based on chiral 1,2-diamines and present their application in the asymmetric addition of 4

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• bicyclic guanidines [7][9][12]. Xiao et al. reported the addition of nitroalkanes to 4-oxo-enoates, using chiral urea derivatives [7]. Miura et al. achieved an asymmetric addition of α,α-disubstituted aldehydes to maleimides catalyzed by primary amine thiourea organocatalyst [13]. Wang et al. reported the

• addition of dialkylmalonates and nitromethane to 4-oxo-4-arylbutenoates catalyzed by N,N´-dioxide-Sc(OTf)3 complexes [8]. Despite these and other successful experimental results, the asymmetric addition of malonates to symmetric aromatic unsaturated 1,4-diketones has not been systematically studied

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

• -disubstituted oxindoles, using cheap and easily available starting materials and simple chiral catalysts to facilitate biological evaluation. We have developed the catalytic asymmetric addition of acrolein, allyltrimethylsilane or difluoroenoxysilanes to isatins to furnish differently substituted

• enantioenriched 3-hydroxyoxindoles [22][23][24]. For the synthesis of chiral 3-aminooxindoles, we developed the first example of catalytic asymmetric addition of nucleophiles to isatin-derived ketoimines using TMSCN [25] and the amination of unprotected 3-prochiral oxindoles using di-tert-butyl azodicarboxylate

• , together with our efforts in the synthesis of unsymmetric 3,3-diaryloxindoles [29], we try to develop a catalytic asymmetric method to enantioenriched 3,3-diaryloxindoles. In 2007, Jørgensen and coworkers pioneered the organocatalytic asymmetric addition reactions to quinones [30][31] which turned out to

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

• the other hand, the asymmetric addition to electrophilic imines of isatins is also an attractive pathway, and a variety of examples have been presented [16][17][18][19][20][21]. Recently, we have developed the asymmetric allylic alkylation reactions [22] with Morita–Baylis–Hillman (MBH) carbonates of

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

• hydrobenzoin·SnCl4 complex 5 promotes the allylboration of hydrocinnamaldehyde with modest enantioselectivity (26% ee) [3], and a hydrobenzoin–ytterbium complex was found to catalyze asymmetric aldol/Evans–Tishchenko reactions [5]. Moreover, the hydrobenzoin dimethyl ether 7 was shown to direct the asymmetric

• addition of organolithium reagents to arene tricarbonylchromium complexes [7] and α,β-unsaturated aldimines [8]. Notably, derivatives of hydrobenzoin in which the aromatic rings have been functionalized in the ortho and ortho' positions often display improved diastereo- or enantioselectivity over the

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• -substituted pyridine derivatives is of particular interest as they are known to be efficient catalysts for the asymmetric addition of zinc organyls to aldehydes [14][46]. Preparation of lactic acid derived pyrid-4-yl nonaflates In the course of our investigations on the scope of the present procedure, we also

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

• 2008 to the present. Keywords: asymmetric addition; catalysis; gold; C−C multiple bonds; tandem reaction; Review 1 Introduction Gold-catalyzed reactions have emerged as a powerful synthetic tool in modern organic synthesis. This past decade has been the boom time for homogeneous gold catalysis, which

• ]. Furthermore, the rapid growing area of tandem reactions has allowed chemists to assemble diverse complex molecular frameworks more conveniently. Although various research efforts have led to gold-catalyzed addition reactions, the area of asymmetric addition has only recently been pioneered. Currently, a broad

• (Scheme 59) [174]. The first step is supposed to be an intramolecular addition of the hydroxy group to the internal carbon of the triple bond, which is similar to the mechanism mentioned above [161][163]. 6 Gold-catalyzed asymmetric addition reactions The chiral ligand used for the transition metal

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

• demonstrated by the catalytic asymmetric additions of thiols to α,β-unsaturated ketones [44]. (R)-LaNa3tris(binaphthoxide) (LSB) catalyses asymmetric addition to cyclic enones (Scheme 16), and products of addition 43 are isolated in good yields and enantiomeric ratios. However, addition to the substituted

• thioether 29. Thioethers 33 prepared from phosphinites 31. Preparation of enantiomerically pure thiol 39. Thioethers prepared by a modified Mitsunobu reaction. Nucleophilic conjugate addition. Asymmetric addition to cyclic enones. Preparation of thioether 45. Catalytic kinetic resolution of the enantiomers

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• gives unprotected cyanohydrins which are prone to racemization. Pre-eminent amongst the synthetic catalysts are metal(salen) complexes, especially those based on titanium (1) and vanadium (2) [1] (Figure 1). Titanium complex 1 will catalyse the asymmetric addition of TMSCN to aromatic aldehydes with 80

• –90% enantiomeric excess at room temperature with just 0.1 mol % of catalyst [11]. Complex 1 also catalyses the asymmetric addition of other cyanide sources including potassium cyanide [12][13][14][15], cyanoformates [15][16][17][18][19][20] and acyl cyanides [17][19][21] to aldehydes, and will accept

• asymmetric addition of TMSCN [26][27][28] and KCN [13] to aldehydes and are more enantioselective, but less reactive than the titanium based catalyst 1. Complexes 1 and 2 have been commercialized [10][29][30], immobilized to facilitate their recycling [31][32][33][34][35][36][37][38][39][40][41][42][43] and