Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• stereoablative approach (Scheme 3) [22][23]. Deprotonation and elimination of the halide in oxindole (±)-8 leads to achiral azaxylylene intermediate 11, which is trapped with malonate nucleophiles to form all-carbon quaternary centers. The overall transformation is unusual since oxindoles are typically

• nucleophilic, but in this case the stereoablative step in the mechanism leads to an electrophilic intermediate. The use of Cu(box) complex 9 rendered the reaction enantioselective, forming C-3 quaternary oxindole 12 in 91% ee (up to 94% ee for related substrates). This strategy is useful for constructing spiro

• reaction was reported by Stoltz for the generation of enantioenriched all-carbon quaternary stereocenters from racemic allyl β-ketoesters (e.g., (±)-20 → (+)-23, Scheme 5) [29]. This particular reaction is especially unusual since the stereoablative step requires scission of a C–C bond at a quaternary

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• extension of the partial structure to 3-indolyl group. These units accounted for six quaternary aromatic carbons and three methoxy groups, requiring the presence of a hexasubstituted benzene ring bearing three methoxy groups and the two indolyl subunits as substituents. Each methoxy signal showed an HMBC

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• distillation reactor loaded with quaternary ammonium strongly basic anion exchange resin and alkali hydroxides: dimethyl carbonate (DMC) is achieved in practically quantitative yields (Scheme 6, bottom). The third and final step is the transesterification of DMC with phenol by a catalytic reactive distillation

• in the ionic liquid were involved in the reaction. It was therefore proposed that an interaction of the quaternary ammonium center with the carbonyl oxygen of glycerol carbonate (GlyC) could weaken the C=O bond (Scheme 15). It is worth mentioning that glycidol was previously obtained at much higher

• (EO), CO2 and methanol was proposed by Li et al., using a series of quaternary ammonium ILs in reactions carried out in an autoclave at 150 °C, and under CO2 pressure (2 MPa) [72]. Even though conversions were good after 8 h, the selectivity toward the desired product was still subject to improvement

Bridgehead vicinal diallylation of norbornene derivatives and extension to propellane derivatives via ring-closing metathesis

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2016, 12, 1877–1883, doi:10.3762/bjoc.12.177

• ring-closing metathesis (RCM) [24][25][26][27][28][29][30][31][32]. Whereas, the diallyl derivative 2 can be derived from a readily available Diels–Alder (DA) adduct 3 through an allylation sequence. Results and Discussion Installation of two C–C bonds to generate quaternary centers in a

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• an azide nucleophile. The synthesis of allyl alcohol C from D-glucose was reported by us earlier. Our synthesis started with the homoallyl alcohol 3 (with defined ‘R’ absolute configuration at the C3-quaternary center) that is obtained from D-glucose as reported earlier by us in 37% overall yield [15

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

• -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

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Antoniego Abrahama 58, 80-307 Gdańsk, Poland Department of Molecular Evolution, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland 10.3762/bjoc.12.138 Abstract This paper presents a study on a series of quaternary

• mutagenicity test; quaternary ammonium salt; Introduction Carbohydrates and alditols occur broadly in nature and possess many biological functions essential to living organisms. Sugars not only contribute as energetic substances, but also serve as building materials for fungi, microbes, plants, and animals

• located at the surface of the cell serve as potential targets for new drugs containing sugars [1][2][4]. Quaternary ammonium salts (QASs) constitute a class of organic compounds with a broad range of applications. A typical QAS consists of a positively charged nitrogen atom with four residues (aliphatic

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

• -carbon quaternary center at the pseudo benzylic position has been achieved via a ‘transition-metal-free’ intramolecular dehydrogenative coupling (IDC). The construction of 2-oxindole moieties was carried out through formation of carbon–carbon bonds using KOt-Bu-catalyzed one pot C-alkylation of β-N

• recently gained immense importance. 2-Oxindoles having all carbon quaternary centres at the pseudobenzylic position are common structural scaffolds in many naturally occurring alkaloids of biological relevance [22][23][24][25]. These heterocyclic motifs especially exist in indole alkaloids with a wide

• equivalents iodine or NIS. Gratifyingly, it was found that a range of β-N-arylamido esters (3a–s) and β-N-arylamido ketones (3t–x) underwent intramolecular dehydrogenative coupling (IDC) under both conditions A and B to afford a wide range of 2-oxindoles (4a–x) having an all-carbon quaternary center in high

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• transition metals to affect asymmetric enyne cycloisomerization [13][14][15][16][17][18][19][20][21][22][23]..In particular, Mikami has disclosed a palladium-catalyzed asymmetric enyne cycloisomerization where a tetrahydrofuran containing a quaternary, all-carbon stereocenter is created in excellent yield

• simple 1,6-enynes displayed a broader scope than Mikami’s palladium system, although none of the examples contained a quaternary stereocenter [25]. Asymmetric enyne cycloisomerization reactions can be extended beyond the construction of 1,4-dienes, depending on the transition metal used and the adjacent

• asymmetric ruthenium-catalyzed cycloisomerization reactions in the literature. In 2011, our research group disclosed the ruthenium-catalyzed redox bicycloisomerization of 1,6- and 1,7-enynes to construct structurally complex [3.1.0] and [4.1.0] bicycles containing vicinal, quaternary all-carbon stereocenters

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• alkaloids of marine origin. Additional features of this route include the stereoselective generation of the central amine core with an appending quaternary center by an asymmetric addition of a Grignard reagent to a chiral tert-butanesulfinyl ketimine following an optimized Ellman protocol and a cross

• features in a variety of potent natural products and bioactive agents [1][2][3][4][5]. As exemplified by the marine natural products manzazidins A and C [2][3][4][5], they may be characterized by diverse configurations, including synthetically challenging quaternary centers. Owing to their pronounced

• ), their unique architecture is characterized by an ester-linked bromopyrrole carboxylic acid and a tetrahydropyrimidine ring in which one of the amino groups is attached to a quaternary carbon center. Due to their intriguing structures in combination with the promising biological properties this class of

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• murine leukemia cells (IC50 0.28 μg/mL) [1]. It is a member of the manzamine alkaloids and has an exquisite molecular structure comprising a 6,6,6,11,13 pentacycle possessing 4 stereogenic centres including one quaternary centre (Figure 1). In 1992, two years before its isolation, Baldwin and Whitehead

• amine, following our well-established protocol [6][7][8][9][10][11][12]. The key quaternary stereocentre of keramaphidin B, we envisaged, would be installed through an enantio- and diastereoselective organocatalytic Michael addition [13][14][15] between pronucleophile 8 and the known substituted furanyl

• stereochemical configuration of the quaternary carbon was established by a diastereoselective Michael addition between a chiral, single enantiomer, cyclic β-amido ester and a nitroolefin, and, in the case of nakadomarin A the reaction could be rendered catalytic using a bifunctional cinchonine-derived urea

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

• have been developed and used in the synthesis of natural products and pharmaceutical agents. Biologically important 3-hydroxyoxindoles with a chiral quaternary center at the 3-position have been successfully accessed utilizing the asymmetric organocatalysis in the last few years. To show recent

• quaternary stereocenter in good yields (up to 98% yield) and with excellent enantioselectivities (up to 99% ee, Scheme 50) [67]. The reactions showed good tolerance to various aromatic and aliphatic β-keto acids as well as substituted 3-hydroxy-3-indolyloxindoles. It was proved that the aryl group at the 3,3

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• conformation of the cyclooctyl ring may also play a role in the selectivity as discussed below. The White group used rhodium dimers as catalysts to form the central quaternary carbon of (+)-codeine (Scheme 9) [62]. This insertion into the benzylic methine of 43 was quite selective, with only a single reported

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

• -Disubstituted (quaternary) amino acids are compounds and/or scaffolds of demanding continuous interest [44] and many stereoselective protocols have been developed for their syntheses [44][45][46][47][48][49][50]. In this field, particularly interesting are N-substituted derivatives, which are potentially good

• therapeutical candidates because of their high lipophilicity and membrane permeability [44][51]. A major catalytic entry to α,α-disubstituted (quaternary) amino acids is the α-functionalization of an appropriate template as, for instance, an α-imino ester or lactone, followed by hydrolysis [49][52][53]; but

• (Scheme 2, compounds 13–15) proceeded with poor diastereocontrol but the results were improved by changing to catalyst C2 [62]. Nonetheless, in both cases the enantioselectivity for the major diastereomer was excellent. Finally, and starting from the corresponding bicyclic imidazolones, quaternary proline

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• ]+ at m/z 411.1997 (calcd for 411.2019). The elemental composition indicated seven double bond equivalents. The 13C NMR spectrum of 1 displayed 21 signals: one CH3 group, seven CH2 groups, nine CH groups and four quaternary carbons. The study of the HSQC NMR correlation map revealed that among the CH2

• oxymethine groups, the hemi-acetal and one of the CH2O (δ 3.65, 3.83/63.0) groups. Furthermore, the quaternary carbons included an α,β-unsaturated carbonyl (δ 165.5), an olefinic carbon (δ 137.5) and two sp3 carbons (δ 47.7 and 53.8). Fifteen carbon shifts remained after the sugar deduction suggesting the

• aglycone to be a sesquiterpene [33]. Based on previous reports, the signals of a CH group at δ 2.12/65.2 (C-10) and a quaternary carbon at δ 53.8 (C-6) observed in the NMR spectra of compound 1 suggested a trixane scaffold for this secondary metabolite [34]. C-10 and C-6 are respectively shared by two and

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

• nitroalkenes and commercially available 1,4-dithiane-2,5-diol to 3,4,5-substituted tetrahydrothiophenes, bearing a quaternary stereocenter, is presented. A secondary amine thiourea derived from (R,R)-1,2-diphenylethylamine was found to be the most effective catalyst when using trans-β-methyl-β-nitrostyrenes

• -Michael/aldol reactions [16][17][18][19][20] enabled the synthesis of differently functionalized tetrahydrothiophenes bearing up to three contiguous chiral centers, including quaternary ones, with good to high control of the diastereo- and enantioselectivity. Surprisingly, to date there has been one

• tetrahydrothiophenes, bearing a quaternary stereocenter, in good yield and moderate enantiocontrol. It has been demonstrated that a simple bifunctional amine thiourea secures a more effective control of the diastereoselectivity than Brønsted base/Lewis acid systems. Data herein illustrated suggest that fine tuning of

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• first tested in the reaction of trans-nitrostyrene (1a) with diethyl malonate (2a), leading to the enantioenriched addition product 4aa with a single stereocenter. In order to the creation of two tertiary-quaternary contiguous stereocenters (5aa) we also used ethyl 2-oxocyclopentanecarboxylate (3a) as

• higher than 90:10, although the stereoselectivity for the reaction leading to 4ag, with two contiguous tertiary–quaternary stereocenters was only moderate (dr 75:25, entry 8 in Table 2). The main difference in those additions was related with the reaction time, because the less reactive malonates (2b and

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• 39 reacted to give the quaternary stereocenters-containing products 42 with high diastereoselectivity (up to > 99:1 dr) and enantioselectivity (up to 90% ee). A bifunctional role played by the catalyst was again envisioned by the authors. In the transition state TS13 the tertiary amine group of the

(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

• proceeded in good to excellent yield and excellent enantioselectivity for almost all of the substrates that were tested. This methodology was further extended in the total synthesis of (−)-mesembrine. This natural product contains a sterically hindered and arylated quaternary carbon center, which was

• multiple contiguous stereocenters, including one quaternary center [35]. The reaction proceeded smoothly and a wide range of products 75 were obtained in good yields and moderate to excellent stereoselectivity (Scheme 26). The authors proposed that the organocatalyst deprotonates substrate 73 to produce a

• enantioselective synthesis of 3,4-dihydrocoumarins 150 bearing an all-carbon spiro-quaternary stereocenter utilizing Takemoto’s organocatalyst 77 (Scheme 48) [69]. The domino process is initiated by a Michael addition followed by acetalization, and subsequent PCC oxidation in an one-pot transformation. In 2012

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

• [27]. The reaction furnished excellent yields of α-hydroxy-α-trifluoromethyl ketones 25 possessing a quaternary stereocentre. The homo-benzoin condensation between two aldehydes is reversible under the reaction conditions. This eventually leads to the selective formation of the observed cross-benzoin

• trifluoromethyl ketones were later developed using the chiral catalyst 27 (Scheme 13) [29]. The electron-deficient triazolium-derived NHC 23 mediated efficient and chemoselective cross-benzoin reactions of aldehydes and α-ketoesters to produce acyloin products endowed with a quaternary stereocentre [30

• afforded chiral quaternary aminooxindole derivatives. The NHC–enal adduct prefers to react via the acyl anion pathway and the competing homoenolate/enolate reactivity was not observed. The sterically non-congested, electron-deficient NHC-catalyst 42 presumably does not hinder bond formation at the catalyst

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

• processes Asymmetric oxidative coupling All carbon quaternary centers are prevalent in both natural and pharmaceutical compounds, but rank amongst the hardest to synthesize in a stereoselective manner. Dixon and co-workers have addressed this through the development of an asymmetric organocatalytic

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• of a dipeptide phosphine catalyst, a wide range of highly functionalized cyclopentenes bearing an all-carbon quaternary center were obtained in moderate to good yields and with good to excellent enantioselectivities. Keywords: [3 + 2] annulation; α-substituted allenoate; dipeptide phosphine

• -sulfonylimines proceeded in an unexpected [3 + 2] annulation mode to afford a cyclopentene ring with an all-carbon quaternary center (Scheme 1) [48]. In recent years our group has developed a family of amino acid-derived bifunctional phosphines and has intensively investigated related asymmetric transformations

• reactions yielded highly functionalized cyclopentenes with an all-carbon quaternary center in moderate to good yields and good to excellent enantioselectivities. Further extension of the reaction reported herein and mechanistic studies are ongoing in our laboratory. Experimental General procedure for the [3

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• quaternary center was to be formed. Ideally, anellation of a cyclopentane would be possible at an indole with an intact enamine partial structure (B, Scheme 1). Such an approach seemed possible, because we had already cyclized 6-prenoylindole to a mixture of cyclopenta[f]- and -[g]indoles in a Nazarov-type

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

• formation of stereogenic quaternary carbon centers by enantioselective MBH reactions has been a fascinating and challenging area, because the compatible electrophiles are always limited to aldehydes or derivatives thereof. Since the first elegant work on the enantioselective MBH reaction between isatins and

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• -pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee). Keywords: asymmetric catalysis; bifunctional catalysts; Henry reaction; organocatalysis; 1H-pyrrole-2,3-diones; Introduction Asymmetric organocatalysis has been

• quaternary stereocenters [35][36][37], we envisioned that the Henry reaction of nitroalkanes with 1H-pyrrole-2,3-diones should take place with a chiral bifunctional amine-thiourea catalyst, leading to 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters (Scheme 1) [14]. Notably, this

• -pyrrole-2,3-diones with a chiral bifunctional amine-thiourea possessing multiple hydrogen-bond donors as the catalyst. With the developed protocol, a range of 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in good yield (up to 75%) and with moderate to good