Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• alcohol derivative 27 in 51% yield as 96:4 mixture of two diastereomers (Scheme 9). Subsequent ring closure of γ-amino alcohol 27 by treatment with mesyl chloride in the presence of triethylamine [53] furnished the N-mesylated pyrrolidine derivative 28 in 65% yield with excellent diastereoselectivity (dr

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• diastereoselectivity (Scheme 2, upper panel). Thus, we were concerned about the possibility of getting a mixture of 5 and 9 under the planned IFCEA cyclization of 6. However, a literature survey indicated that cis-diastereoselective synthesis of related tetracyclic molecules via intramolecular Friedel–Crafts

• from commercially available 1-tetralone (8) in six steps (Scheme S1, Supporting Information File 1). Substrate (±)-6a bearing a pendant 4-methoxyphenoxy group with a moderately electron-rich reacting site was expected to undergo IFCEA cyclization in high regio- and diastereoselectivity to give the

• products were clean (Supporting Information File 1) and the cis-stereochemistry at the ring junction of the remaining products were tentatively confirmed by comparing their 1H and 13C NMR spectra with that of (±)-5k. The obsereved cis-diastereoselectivity in this work is consistent with the reported

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Davide Brenna,
• Elisabetta Massolo,
• Alessandra Puglisi,
• Sergio Rossi,
• Giuseppe Celentano,
• Maurizio Benaglia and
• Vito Capriati

Beilstein J. Org. Chem. 2016, 12, 2620–2626, doi:10.3762/bjoc.12.258

• diastereoselectivity of the process could be tuned, thereby leading to the formation, under different experimental conditions, to both the syn- and the anti-isomer with very high enantioselectivity. The excess of cyclohexanone was recovered and reused, and the reaction could be run and the product isolated without the

• hours and with high conversion (≥95%) in all tested DESs (A–E, Table 2, entries 1–5). While low diastereoselectivity was observed in DES A (Table 2, entry 1), anti-stereoselectivity (up to 85:15) and high enantiomeric excess in favour of the anti isomer (up to 92% ee) were instead detected running the

• completely in only 15 h, and afforded a clean product (aldol 1, Scheme 2) that was easily isolated by evaporation of excess cyclohexanone, with high anti-diastereoselectivity (up to 90:10), and enantioselectivity (up to 92%) for the major anti isomer. By performing the reaction with 4-chlorobenzaldehyde in

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• ]. Although this approach is challenging in terms of diastereoselectivity (up to eight possible diastereoisomers), it enables a rapid increase of molecular complexity. The major diastereoisomer of 11 can be then subjected to the assisted tandem catalytic sequence: RCM reaction, followed by the reuse of the

• relation to the neighbouring benzoyl group). Compounds 27 and 29 were subjected to Evans–Saksena reduction with NaBH(OAc)3 in MeCN/THF in the presence of AcOH (Scheme 8). Under these conditions, derivative 30 was obtained from 27 in good yield (67%) and with high diastereoselectivity (dr = 10:1

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• and B showed good agreement with those of the isolated flavonoid alkaloids [2]. Similarly to the natural route, no diastereoselectivity occurred in this sequence, as proven by the separation of the stereoisomers by chiral HPLC and by the integration or deconvolution of NMR signals of Hy-3 recorded in

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• experimental conditions (temperature and alcoholic solvent) a different diastereoselectivity has been reported in the reduction of the same protected inosose [45][48]. This highlights how subtle changes in the inosose structure and/or in the experimental conditions affect the stereo-outcome of the reduction

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• on the stereoselective formation of aziridine 27. This key reaction proceeded from allylglycine 28 in 28% yield to give a 7:3 mixture in favour of the S,S diastereomer. Attempted optimisation of the yield and diastereoselectivity afforded no improvement. The synthesis continued with aziridine opening

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• /bjoc.12.222 Abstract A dipeptide-based urea-amide tertiary amine (DP-UAA) was shown to be an effective Brønsted base catalyst for the first asymmetric annulation reaction between 5H-thiazol-4-ones and N-itaconimides. High levels of enantioselectivity (up to 99% ee) and diastereoselectivity (>19:1 dr

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• -triazine moieties has been developed. The method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to 6-benzylideneimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7-diones. Keywords: azomethine ylides; cycloaddition; diastereoselectivity

• interest to synthesize the other types of spiro compounds such as the 2,3’-spiropyrrolidinyloxindole structure which is isosteric with the 3,3’-spiropyrrolidinyloxindole and to study the diastereoselectivity of its formation. It could be expected that the cycloaddition of more bulky azomethine ylides

• diastereoselectivity of the cycloaddition were elucidated by spectroscopic methods and single crystal X-ray diffraction. The cycloadducts 4a–t were characterized by IR, NMR, and HRMS analytical methods. The IR spectra of compounds 4 showed three intense absorption bands at 1728–1697, 1709–1680 (in some cases instead

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• amphidinolide F (24), was accessible in good overall yield and high diastereoselectivity (dr ≈ 95:5) in only four steps (Scheme 7). Oxidative cyclizations in the synthesis of annonaceous acetogenins cis-Solamin A cis-Solamin represents a typical mono-THF acetogenin, originally isolated from the roots of the

• rings were introduced with excellent diastereoselectivity in a single step transformation at the final stages of the total syntheses of rollidecin C (69) and D (70) (Scheme 14). Similar rhenium-mediated type C oxidative cyclizations were also successfully applied in total syntheses of further

• ] provided C2-symmetric diol 72 (R = H) in high selectivity (ee >94%). Subsequent Co(II)-mediated oxidative type B’ cyclization of dienediol 72 (R = H) proceeded in good yield (78%) and with high diastereoselectivity (de 96%) to give C2-symmetric bis-THF product 73 (Scheme 15). The natural product was then

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• -butylphenyl group, delivered a critical improvement in diastereoselectivity, affording 4aa quantitatively and establishing consecutive quaternary and tertiary stereocenters with almost complete fidelity (Table 1, entry 3). Further examination of the reactions under the influence of 1d, having 3,5-bis

• properties of both oxindoles 2 and N-Boc aldimines 3, but reactivity and diastereoselectivity sometimes fluctuated depending on the structure of these substrates. While significant variation in the imine substituents was feasible, the introduction of electron-withdrawing groups at the meta-position slightly

• reduced diastereoselectivity (Table 2, entries 1–4). Sterically demanding 2-tolualdehyde-derived imine 3f served as a good electrophile and the corresponding Mannich adduct 4af was isolated as virtually a single stereoisomer (Table 2, entry 5). 3-Thiophenyl aldimine 3g was also well tolerated, but a

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• TCNE and ketones) with aldehydes in an acidic media. An unusual process of quasi hydrolysis of the cyano group was observed in the course of the described regio- and diastereoselective transformation. Keywords: diastereoselectivity; 3,4-dihydro-2H-pyran-4-carboxamide; nitriles; pyran; quasi-hydrolysis

• under subsequent formation of the intermediate 2,7-dioxabicyclo[3.2.1]octane derivative 3. This reaction was separately described by us previously and it is the crucial reason for the diastereoselectivity of the whole transformation [21][22]. Further acid-catalyzed addition of water to the imino group

• exceptional diastereoselectivity based on the reaction of available 4-oxoalkane-1,1,2,2-tetracarbonitriles (adducts of TCNE and ketones) with aldehydes in acidic media. Unusual processes of regiospecific quasi-hydrolysis of a cyano group and abnormal resistance of the imine moiety to be hydrolyzed in aqueous

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• all cases, the reaction proceeded with full diastereoselectivity, affording the product with a cis relationship between the aryl substituent and the peptide side chain as shown by NOE studies, which are summarized in Figure 1 for compound 2f. One example of a reaction leading to an alkyl substituent

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• S/R ratios are considerable high in the absence of Lewis acids. The high inductive capacity is interpreted in terms of the fact that the conformation of the dienophile is fixed by a π-stacking interaction. The reactions promoted by Et2AlCl produced the reversed endo S/R diastereoselectivity with a

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• further optimization of reaction conditions found that the addition of additional 0.5 equiv 1a into the reaction mixture in 4 portions significantly improved the reaction yield (83%, Table 2, entry 13). In order to improve the diastereoselectivity of this reaction, other cyclopentanes used in Trost’s

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• through the one-pot reaction of phosphonodithioacetate 165, aromatic aldehydes 166 and dienophiles 167 in the presence of piperidine in refluxing toluene (Scheme 36) [74]. The new phosphorylated cycloadducts were isolated in excellent yields and with a trans- or cis-diastereoselectivity. 4 Metal-catalyzed

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• ]). Singular contributions employing different systems were contributed by other groups [27][28][29]. Scheme 8 shows a typical example of Solé et al. [23], related to our systems, furnishing a tricyclic compound in good yield with moderate diastereoselectivity. The transformations described in the present

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

• alkaloid amine (cat. 42, 10 mol %) and CPA (cat. 43, 30 mol %), affording the desired products in moderate to good yields (61–89% yields) and with good diastereoselectivities (up to 10/1 dr) and excellent enantioselectivities (up to 99% ee, Scheme 64) [81]. The poor yield, diastereoselectivity and

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

• generated from alkynes can produce bridged bicycles from C–H bond insertion (Scheme 23) [96]. This was first implemented by transannular insertion via 107 to give the bicyclo[3.2.1]octane 108. The diastereoselectivity of the process was not reported. Again, dual gold catalysts were used with a pyridinium

• catalyst control for these reactions should be pursued. Ideally, the catalyst would dictate the diastereoselectivity, the enantioselectivity, and the location of C–H bond insertion to provide any of the possible product isomers selectively on demand. Bridged polycyclic natural products. Strategic

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

• demonstrated to be either less reactive and/or less stereoselective in their addition reaction to nitrostyrene thus affording the corresponding Michael adducts with no diastereoselectivity and/or poor enantioselectivity (Scheme 3). Useful applications of the Michael adducts coming from the Michael addition of

• –C and C–heteroatom bonds [112] and have been used in many synthetic applications [113]. However one of the main limitations in the area is the lack of highly diastereo- and enantioselective protocols. In this context, particularly difficult has been to achieve high diastereoselectivity, and only a

• -catalyzed allylation substitution reaction of oxazol-4(5H)-ones and thiazol-4(5H)-ones to afford enantioenriched tertiary alcohols and thioethers (Scheme 19) [42]. In this case the diastereoselectivity is controlled by cations, in contrast to most of the described protocols wherein it is modulated by anions

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• transformation was regio and stereoselective where the main product was trans-γ-lactam (56). The chiral rhodium complexes (S)-17, (S)-18 and (S)-23 were also evaluated and yielded similar regio- and diastereoselectivity, however, with lower enantioselectivity when compared to the bis(oxazoline)/CuCl2/NaBARF

• low temperatures to affords the product in high yields and enantioselectivity (Scheme 12). The same catalytic system was applied to carbenoid insertions into tetrahydrofuran C(sp3)–H bonds (Scheme 13). The reaction afforded the desired product in a regioselective way and high diastereoselectivity

• (sp3)–H bonds (Scheme 18). In both cases, was only observed the formation of the regioisomer derived from carbenoid insertion into the primary allylic position with excellent yield and high diastereoselectivity. For the steroidal substrate, the catalyst (R)-74 favored the formation of a new center with

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• muraymycin core structure (Scheme 6) [78][99]. The key step of their route was a sulfur-ylide reaction with high substrate-controlled diastereoselectivity [100][101][102]. This epoxide-forming sulfur-ylide reaction had been established before by Sarabia et al. [103][104]. After some initial confusion

• regarding the stereochemical configuration of the epoxide product, it could be unambiguously proven that the transformation of uridine-5'-aldehyde 44 with sulfonium salt 45 under basic conditions furnished epoxide 46 with high diastereoselectivity (Scheme 6). Subsequent ring opening of this epoxide with

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• substituents could be installed on the α-position (yield of the major product was given). Notably, when (+)-sparteine surrogate 28 was used as a ligand, product 38 was produced in 90% yield with 95:5 diastereoselectivity, but once the chiral amine ligand was simply switched from 28 to (−)-sparteine (21

• ), product 39 was produced in only 49% yield with poor diastereoselectivity (67:33). This result indicates a mismatched case of (−)-sparteine and the (S)-α-methylbenzyl group even though the chiral center of the “chiral auxiliary” is quite far away from the newly established chiral center. This issue is

• the diamine switch strategy and α-methylbenzyl chiral auxiliary strategy has been reported to give the best results and produce 51 in 70% yield and 90:10 diastereoselectivity (Figure 11, reaction 3). O’Brien and co-workers also reported a stereoselective synthesis of enantiopure 2,6-trans- and 2,5

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• benzal bromide was used instead, yields were near 60% in selected polar-aprotic solvents, i.e., ~93% yield per bond and ~88% diastereoselectivity [14][15][16]. Unfortunately a reviewer at the journal that we first submitted our manuscript to was also a doubter, even after we sent all the spectra, crystal