A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• effects: firstly, reversible hydroxylation means that alcohol epimers 2 may convert to fluoride epimers 8 via cation 10 (pathway (a)); secondly, reversible fluorination and/or hydroxylation means that the diastereoselectivity of formation and/or 2 may be governed by product stability and not inherent

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

• /nitroaldol reaction and herein we report our preliminary results. Results and Discussion According to the literature data, low control of the diastereoselectivity was observed in the cascade reaction of 1,4-dithiane-2,5-diol with trans-β-nitrostyrenes, and in the case of (E)-1-aryl-2-nitropropene all four

• less active, affording a comparable level of diastereoselectivity than compound VII, but a lower ee value for major diastereoisomer 7a was measured (Table 1, entry 14). Moreover, the opposite enantiomer of product 7a was preferentially obtained, thus suggesting that the nature of the alkyl group on the

• predicted relative free energies for 10, 11 and 12 fall within a range of 0.1 kcal/mol. Pleasingly, a solvent screening for the cascade reaction carried out on compound 2a with catalyst VII enabled to improve the diastereoselectivity as only 7a/8a were detected in 75:25 ratio and the enantiocontrol

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

• diastereoselectivity for the reaction of 1a with 2g (dr 74:26), but the yields for the reactions with 2-substituted malonates (2b–d) were only moderate (entries 9–11 in Table 2). Next, we extend the study to the reaction of different β-functionalized cycloalkanones (3a–c), 2-acetylcyclopentanone (3d), and 2-acetyl-γ

• -lactone (3e) with nitrostyrene derivatives 1a–d (Scheme 3 and Table 3). The electronic nature of the nitroolefins only affects the yield and the reaction time, being longer as the donating effect of the substituent increases, but maintaining good diastereoselectivity and excellent enantioselectivity for

• ) reacted very well with 1a, leading to 5ae in excellent yield and enantioselectivity, but only moderate diastereoselectivity (dr 70:30, Table 3, entry 10). To test the recyclability of catalyst V we choose the reaction of 1a with 3a in neat conditions and 5 mol % of catalyst as model. Once the reaction had

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• to the stereoselective glycoside synthesis. The final products were obtained by conventional Zemplén deacetylation. Keywords: diastereoselectivity; p-hydroxyphenylalkyl glycosides; mild promoters; natural products; 1,2-trans-glycosylation; Introduction Arylalkyl (substituted benzyl, phenethyl 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

• very low catalytic charge (1 mol %), affording a broad scope of the enantiomerically enriched β-nitroalkyl products 38. A possible drawback of the method would be the low diastereoselectivity generally achieved for the nonsymmetrical 1,3-dicarbonyl compounds 36. In order to understand the role of the

• transition state TS15 based upon Seebach’s model [59] was envisioned as a plausible activation mode to explain the high asymmetric induction observed and the syn-diastereoselectivity exhibited by the catalyst 56. First, the activation of the ketone via enamine formation is produced. Furthermore, the acidic

(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

• was found to be the optimum acid for the second step of the reaction. Products were obtained in good to excellent yields (64–99%), with >20:1 diastereoselectivity and excellent values of up to 98% ee. Employing the same catalyst as before, organocatalyst 27, another synthesis of the bridged core 30

• dienophile 32, using compound 34 as the catalyst (Scheme 12) [23]. This reaction provided products in 84–99% yield and with a diastereoselectivity of up to >20:1 and excellent enantioselectivity (88–99% ee). In 2015, Dixon, Paton and co-workers demonstrated an elegant route to morphan skeletons, utilizing

• is highly noted that the difference to the moiety at the 4-position of the pyrrolidine ring, where a fluorine atom exists, gives to the organocatalyst 50 the ability to catalyze this tandem Michael–Henry reaction in brine, giving excellent diastereoselectivity and enantiomeric excess, unlike the

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

• -keto esters afforded fully substituted β-halo-α-glycolic acid derivatives in high diastereoselectivity and enantioselectivity [32]. The NHC generated from the amino indanol-derived chiral triazolium salt 29 provided the best results (Scheme 16). A variety of aromatic aldehydes and a series of β-halo α

• influence of these catalysts on the diastereoselectivity of the reaction was also studied using NMR techniques. An NHC-catalysed intramolecular benzoin condensation of carbohydrate-derived dialdehydes has been applied for the construction of carbocyclic sugars. Diastereoselective benzoin reactions of manno

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

• and position of the substituents on the phenyl ring (Table 3, entries 3–10). When the substituent was in the ortho-position of the phenyl ring of the R2 group, a diastereoselectivity was observed that may be due to the steric hindrance of ortho substituents led to the atropisomers (Table 3, entry 3

• desired product in 41% and 48% ee (Table 3, entry 12). The introduction of a phenyl group on the nitrogen atom had a negative effect on the reaction (Table 3, entry 13). Nitroethane was also used to react with 1H-pyrrole-2,3-dione 1b, and a good diastereoselectivity was achieved with an unfavorable yield

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• -substituted hexahydroisoindolinones was developed by using bifunctional tertiary amine-thioureas as powerful catalysts. As far as we know, there is no efficient synthetic method developed toward fully-substituted hexahydroisoindolinones. The products were obtained in good yield and diastereoselectivity. The

• the product were seen when toluene or methanol was used as the solvent (Table 1, entries 12 and 13). Furthermore, raising the reaction temperature was not beneficial for the diastereoselectivity of the reaction (Table 1, entry 14). With the optimal conditions in hand, we next examined the reaction

• scope (Table 2). All reactions afforded the corresponding products 3a–t with medium to good yield and diastereoselectivity using the simple protocol at room temperature. To our delight, with our optimized reaction system, various types of substrates 1 showed very good reaction activities. Different

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• , the usefulness of this approach relies on an efficient and diversity-oriented preparation of the required amines in high enantiomeric excess. Chiral aminoalcohols can be ideal substrates for diastereoselective Ugi reactions: the additional hydroxy group can both help in modulating diastereoselectivity

• -aminoalcohols have been proved by Nenajdenko and co-workers to be able to induce good levels of diastereoselectivity in the Ugi reaction [17]. Our attention was drawn by 1,3-aminoalcohols of general formula 5 (Scheme 1), which can be obtained by List's organocatalytic Mannich-type reaction of aldehydes with N

• moderate diastereoselectivity was achieved (Table 1, entry 1), which could be increased by changing the solvent to trifluoroethanol, especially effective at 0 °C. Considering the recent work by Nenajdenko et al. [17], we explored the usage of Lewis acids in an aprotic solvent in order to further improve

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• this transformation. Furthermore, 1,2-disubstituted olefins were also viable substrates (Table 2, entries 9–11). Particularly exciting is the formation of 6j and 6k in excellent diastereoselectivity. In contrast, acyclic 1,2-oxyamino product 6i was formed as a 1:1 mixture of two diastereomers. These

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

• N-tert-butanesulfinylimine intermediates [11][12]. Due to its high diastereoselectivity and convenient cleavage of the N-tert-butanesulfinyl group, it has become an excellent chiral auxiliary in the synthesis of chiral amine compounds [13]. This work was devoted to develop an efficient synthetic

• after reduction, the basicity resulting from NaBH4 might lead to the denaphthalenyloxylation. Therefore, AcOH was used as an additive in the reaction. The results showed that the denaphthalenyloxylation was almost negligible, but the diastereoselectivity was not good enough (Table 1, entry 5). Although

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• . The first attempt of an intermolecular asymmetric Ullmann coupling for the formation of biaryls was reported by Miyano and co-workers in 1980. The authors used a chiral ester group as auxiliary but only poor diastereoselectivity (13% de) was obtained [15]. A few years later, the same group took

• stereogenic centers, derived from tartaric acid, giving the product as a single isomer in good yield (Scheme 11). Sugimura et al. [31] expanded this method by introducing chiral 1,3-diol-derived tethers into the substrates, delivering the corresponding coupling products in excellent diastereoselectivity

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• -glucopyranosyl azide and phenylacetylene reacted under CuI and the secondary amine-functionalized polysiloxane catalytic system, where the desired chiral bitriazole 23 was obtained with good diastereoselectivity (85:15). Subsequently, the authors used this method to construct the novel, cyclic 5,5’-bitriazole 24

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

• with acryloyl chloride gave ester 87 and a ring-closing metathesis reaction using Grubbs second generation catalyst [50] furnished an α,β-unsaturated lactone. Subsequent 1,4-addition of the cuprate derived from alkylmagnesium chloride 88 provided the trans-product with excellent diastereoselectivity

• % yield and with high diastereoselectivity (dr = 94:6). Carboxylic acid 129 was then converted to intermediate 130 in seven further steps. An intramolecular coupling between the formate ester and the allylic bromide provided lactol 131 in excellent stereoselectivity (dr > 95:5). The preparation of

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• transformation to proceed with a yield of 50% and an excellent diastereoselectivity (de 94%). The Hoveyda group was also interested in developing efficient methods for the generation of quaternary stereogenic centers from Michael acceptors via copper-catalyzed 1,4-ACA of diethylzinc onto cyclic Michael acceptors

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• rise to the desired cycloadducts 3b and 3'b in good yields but without any diastereoselectivity when we performed the reaction in chloroform (Table 2, entry 3). Nevertheless, switching from chloroform to toluene as reaction solvent, results in a total regain of diastereoselectivity without loss of

• . Moreover, the high diastereoselectivity observed with indoles 1a–h in toluene as solvent, accounts for a concerted or a pseudoconcerted mechanism in which the formation of an endo transition state and thus of the final 2,3-trans adducts 3a–h is preferred (Scheme 3). Thus bond formation between the 1,4

• diastereoselectivity is not affected by the reaction medium (chloroform vs toluene). Moving to the alkyl-substituted vinylindole 1b, the reaction yields equimolecular amounts of both conceivable diastereoisomers in CHCl3 whereas toluene is the optimal solvent to achieve high diastereoselection (see Table 2, entries 3

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• Hoveyda-type complexes in cross metathesis of methyl oleate with ethylene [16]. Complexes containing iodide lead to products of asymmetric OM with better enantio- and diastereoselectivity, but this came at the price of lower activity [17]. In the past few years the replacement of chloride ligands created

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• linear bicyclic scaffolds in a very simple manner with moderate to good levels of diastereoselectivity. This methodology constitutes one of the few examples that employ olefins differently than ethylene in tandem CEYM–IMDAR protocols. Keywords: bicyclic frameworks; cross enyne metathesis; Diels–Alder

• with our previous assumption that the cis-triene does not undergo the IMDAR. Diolefinic amides 8c and 8d bearing the 2-naphthyl and 2-furyl substituents, respectively, rendered the corresponding bicyclic products 10c and 10d in acceptable yields (47 and 68%) and moderate diastereoselectivity (Table 3

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• is obtained, among the possible three coupling products only the ß,ß-linked dimer is found. The diastereoselectivity is moderate, one obtains two main diastereomers (about 70–80% of the mixture of isomers) and one of the six possible diastereomers was not found. The use of an undivided cell

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• the auxiliary that locked the conformation of the molecule. The excess Grignard reagent would add to the double bond from the less sterically hindered side, thus leading to the diastereoselectivity. Note that when using Grignard reagents as nucleophiles in CA reactions, the possibility of the 1,2

• provided an increase in diastereoselectivity and a higher yield of the product after deprotection of the sultam group over the Oppolzer auxiliary (Scheme 3). The Evans auxiliary 6 has been used extensively in several asymmetric transformations such alkylations, allylations and most notably for aldol

• -oxazolidinones [43] (Scheme 4). The diastereoselectivity of the reactions using the Evans auxiliary is attributed to the ability of the Lewis acidic metal to form a complex between the two carbonyl oxygens (Figure 3). This Lewis acid complex locks the molecule into one conformation, thus facilitating the

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• additional substituent in position 8 is described. Due to 1,3-diaxial interactions a pronounced diastereoselectivity for the menthylamines is found. Keywords: cathodic reduction; chiral amines; electrosynthesis; menthylamines; oximes; Introduction Optically active amines serve as powerful and versatile

• converted to 3 in attractive diastereoselectivity (see Scheme 2, pathway II) [45]. However, the necessity for excess amounts of sodium metal constitutes a major drawback. Consequently, we also investigated on electrochemical alternatives for the reduction of (−)-menthone oxime. In this context, we found

• effect of the substituent in position 8 onto the diastereoselectivity of the reduction (compare Scheme 4, dr = 2.4). Since lead was distinctly the prime cathode material it was used throughout all further investigations. To determine the influence by the temperature onto the selectivity, the reaction was

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• diastereoselectivity. As expected, a cyclic β-halo-α,β unsaturated aldehyde substrate led to the respective tricyclic lactone, the core structure of strigolactone [12]. Bertrand synthesized β-carboxylic acid-γ-lactones in high yields but with low diastereoselectivity via a dialkylzinc-mediated radical addition to the

• ligands had little effect on the diastereoselectivity (Table 2, entries 5–10). The anti-isomer lactones were more favorable when replacing acrylate with crotonate (Table 2, entry 11). Our previous results suggested that higher diastereoselectivity could be achieved with hindered acrylate in the copper

• hydride-catalyzed reductive aldolization of acetophenone [19]. Therefore, tert-butyl acrylate (1d) was used to replace methyl acrylate, and several biphosphorous ligands were screened for improving the diastereoselectivity (Table 3). Diastereomers of 3da were separated, which were subjected to further

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

•  2, entry 8) while the reaction using PhSeBr under conventional methods gave the product in 76% yield and a diastereoselectivity of 73:27 (threo:erythro). When alkyl-substituted 1,4-dienols are used, the formation of tetrahydrofuran or pyran derivatives can be observed (Table 2, entries 9 and 10

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

• introduction of the nucleophile to the C–X bond that contains the electroauxiliary (Scheme 4). Similarly, α-silyl-carbamates undergo low potential anodic oxidation reactions with complete regiocontrol and in special cases diastereoselectivity [34][35]. Interestingly, a porous graphite felt anode and a

• ]. The proposed formation of a bicyclic intermediate 18 resulting from a cycloaddition reaction would enhance the diastereoselectivity of the hydration step compared to an acyclic intermediate that would be formed in the step-wise mechanism to 18. The authors’ suggest the step-wise mechanism does play a

• role in reducing the diastereoselectivity of the reaction when the alkene is aryl- or alkyl-substituted. The hydration step can occur via pathway a or b to afford 17 (dr ca. 3:2). The N-acyliminium ions formed during an anodic oxidation of a silyl auxiliary can be coupled to a radical pathway using a