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

• enduracididine Although several synthetic approaches to enduracididine and its derivatives have been published, the discovery of teixobactin (17) has reignited interest in the synthesis of this unnatural amino acid. Synthesis of enduracididine by Shiba et al.: The first diastereoselective synthesis of

• with isothiourea 33 followed by mesyl chloride afforded cyclic guanidine 72 in 70% yield. Silyl deprotection, Swern oxidation and Still–Gennari olefination afforded Z-alkene 73. Diastereoselective dihydroxylation of 73 followed by treatment with 1,1'-thiocarbonyldiimidazole (TCDI) and sodium azide

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

• class of sulfur-containing pro-nucleophiles in a highly enantio- and diastereoselective conjugate addition to nitroalkenes, providing α,α-disubstituted α-mercapto carboxylic acids [5]. Since then, several asymmetric variants using 5H-thiazol-4-ones as nucleophiles have been disclosed; such as amination

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

• regio- and diastereoselective one-pot method for the synthesis of new polynuclear dispiroheterocyclic systems with five stereogenic centers (dispiro[imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-6,3′-pyrrolidine-2′,3′′-indoles]) comprising pyrrolidinyloxindole and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4

• generated from isatins and sarcosine to benzylidene derivatives of the same imidazothiazolotriazine will proceed from the less sterically hindered side [41] (anti attack). Herein, we report a regio- and diastereoselective one-pot method for the synthesis of a novel class of polynuclear dispiroheterocyclic

• phase (see Supporting Information File 1). Thus, the cycloaddition of azomethine ylides was found to be highly regioselective, as the electron-rich carbon of the dipole adds to the β-carbon of the α,β-unsaturated moiety of dipolarophile 1. Further the reaction is diastereoselective, as only one

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

• protocols using the three different d0-metals are highly diastereoselective (vide infra) and have been shown over the past decades to be applicable to a broad range of starting materials. Mechanistic aspects, stereochemistry and substrate scope of the direct oxidative diene cyclization Intrigued by the

• for divalent cations. It is commonly used to both modify intracellular Ca2+ concentrations and to investigate Ca2+ transport across biological membranes [58]. In 2011, Kocienski and co-workers reported on a formal synthesis of ionomycin using an auxiliary-directed, diastereoselective permanganate

• -solamin A (29) and B using the diastereoselective, auxiliary-controlled, permanganate-promoted type A oxidative cyclization of 1,5-dienes to create the THF diol backbone and to introduce four of the five stereogenic centers present in these mono-THF acetogenins (left, Scheme 8) [76][78]. Starting from

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

• University, Leninskie gory 1, Moscow, Russia 10.3762/bjoc.12.198 Abstract An efficient diastereoselective approach for the synthesis of functionalized 3,4-dihydro-2H-pyran-4-carboxamides with variable frame was developed based on the reaction of available 4-oxoalkane-1,1,2,2-tetracarbonitriles (adducts of

• 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

• diastereoselective cascade reaction [23]. The crucial stage of the described transformation is the formation of a pyran-4-carboxamide intermediate. A trace amount of it was isolated accidentally and we could not repeat this procedure and characterize the compound by spectra. Results and Discussion In continuation of

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

• Asymmetric (chiral) hetero-Diels–Alder reactions in a stereoselective (enantioselective or diastereoselective) manner have become very popular in the last decade. Pioneering works by Kresze and Vasella [56][94][105] using carbohydrate-based α-chloronitroso agents and Kirby [14] using acylnitroso compounds

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• a diversity of multicomponent reactions, which includes trapping of onium ylides by different electrophiles, such as activated С=С, С=O, C=N and other bonds [9]. A plethora of works aimed at realization of this “metal–carbene” methodology appeared in the last few years. Thus a diastereoselective

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

• -piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions

• functionalized DKP derivatives [20][21][22]. In this context, we describe here an efficient regio- and diastereoselective one-pot three-component assembly of trisubstituted aziridines possessing a free NH group and containing a peptidic or peptide-like side chain. Furthermore, we describe the conversion of these

• double bond in readily available 3-arylmethylene-2,5-piperazinediones, followed by a domino process involving three consecutive nucleophilic attacks that achieve regioselective opening of the diketopiperazine ring and diastereoselective generation of the aziridine ring. The protocol described here

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

• diastereoselective as predicted by the Alder´s rule. The reaction between 6a or 6b and cyclopentadiene carried out at room temperature showed a high stereoselectivity (Table 2, entries 1 and 3, respectively). These results are similar to the ones previously reported for 6c (endo R/S 13:87) [16]. Noticeably, the endo

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

• ) [39]. 2.2.3 Isoindolinylphosphonates: A one-pot diastereoselective multicomponent reaction towards (isoindolin-1-one-3-yl)phosphonates has been developed by Ordóñez et al. (Scheme 14) [40]. The reaction of 2-formylbenzoic acid (55) with (S)- or (R)-amines 56 and dimethyl phosphonate under solvent and

• reaction followed by an intramolecular ring-closing reaction for the synthesis of diethyl (2-methyl-2-pyrrolidinyl)phosphonate. Synthesis of (S)-piperidin-2-phosphonic acid through an asymmetric Kabachnik–Fields reaction. A modified diastereoselective Kabachnik–Fields reaction for the synthesis of

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

• efficient one-pot formation of three consecutive carbon–carbon bonds. X-ray crystal structure determination of (±)-19b proved the outcome of the reaction unambiguously. It was noteworthy to observe Pd-catalyzed highly enantio-, chemo-, and diastereoselective double decarboxylative allylations on dimeric β-N

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

• Pavol Jakubec Alistair J. M. Farley Darren J. Dixon Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom 10.3762/bjoc.12.104 Abstract The enantio- and diastereoselective Michael addition of a δ-valerolactone-derived

• 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

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

• very narrow range of nucleophiles have been reported to be efficient in this regard (α,α-disubstituted aldehydes [114] and β-ketoesters [115] among others). With the aim of expanding the nucleophile scope of this transformation, in 2014 Hartwig et al. reported a highly diastereoselective iridium

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

• chiral catalyst to enantioselective carbenoid insertion into the endocyclic allylic C(sp3)–H bond. Regio- and enantioselective carbenoid insertion into the C(sp3)–H bond catalyzed by a new bulky cyclopropylcarboxylate-based chiral dirhodium complex (R)-74. Regio and diastereoselective carbenoid insertion

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• aldehydes in the presence of metal halides to furnish tetrahydro-2H-pyran-2,4-diols in a highly diastereoselective manner, is investigated thoroughly by experiments and computations. The reaction was also successfully implemented on a flow micro reactor system. Keywords: DFT; diastereoselective reaction

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

• -catalyzed asymmetric allylic alkylation [24]. The most straightforward and attractive way of synthesizing α-carbon-substituted piperazines is the selective (regioselective, diastereoselective, and enantioselective) activation and functionalization of the existing C–H bonds of piperazine substrates (Figure 2

• overcome these intrinsic reactivity issues, new synthetic methods and novel catalyst systems are necessary. These engagements are important because general and practical regioselective, diastereoselective, and enantioselective C–H functionalizations of piperazines are expected to significantly enhance the

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

• report on a dynamic system combining a 1,1,3,3-tetramethylguanidine (TMG)/ZnI2-catalyzed diastereoselective cascade sulfa-Michael/nitroaldol reaction followed by lipases catalyzed kinetic resolution using two representative trans-β-methyl-β-nitrostyrenes and 1,4-dithiane-2,5-diol as reagents [21]. One

•  1) [24]. Finally, catalyst VII was checked in the reaction of alkene 3 under the same conditions (Table 1, entry 15). After a longer reaction time, diastereoisomers 10–12 were isolated with poor diastereomeric ratio and major isomer 11 was recoverd with 42% ee [25]. The diastereoselective ratios

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

• . The addition of nitroketone was totally diastereoselective and highly enantioselective (entries 1–12 in Table 4), whereas both the diastero- and enantioselectivities were moderate for the addition of nitroester (Table 4, entries 13–15). Additionally, supported catalyst V was able to promote more

(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

• desired products in excellent yields and selectivities. In order to broaden the utility of this methodology, the authors reduced the nitro group to an amine. The product was in situ transformed to the tricyclic product 102, through a diastereoselective reductive amination, that controlled the

• epimerization to the sole product 193. Their postulation is based on the fact that Henry reactions are typically reversible, so 194 and 195 could be involved in a retro-Henry and subsequent diastereoselective Henry reaction, where the stereochemical outcome is inducted by the C2 stereochemistry. This is further

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

• , diastereoselective reduction of the cross-benzoin products with NaBH4 afforded valuable syn-diol products. Goodman and Johnson disclosed a dynamic kinetic resolution of β-halo-α-ketoesters via NHC-catalysed asymmetric cross-benzoin reaction. Here, the cross-benzoin reaction of aromatic aldehydes with β-stereogenic-α

• ]. Meanwhile, the Breslow intermediate is produced from the aldehyde by the thiazolium 31-derived NHC. The union of these two reactive intermediates furnished α-amidoketones 32 in excellent yields (Scheme 18). A diastereoselective [4 + 1] annulation of phthalaldehyde with imines leading to the formation of cis

• 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

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

• -bonding moiety of the 6’-OH in the catalyst is essential in directing the reaction towards the anti-diastereoselective pathway. Secondly, the solvent was critical in the diastereocontrol of the reaction. This is put down to the fact that the solvent can have an important influence on the conformation of

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• catalyst of diastereoselective aza-Diels–Alder reactions [68] (Figure 14). While, the structure of the “chiral boron reagent” still remains unknown during our investigation of analogues we discovered a very interesting three-component self-assembly. Chiral binol, a chiral amine and 2-formylbenzeneboronic

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• Charlotte Collet Francoise Chretien Yves Chapleur Sandrine Lamande-Langle Université de Lorraine, Vandoeuvre-les-Nancy F-54500, France CNRS, UMR 7565, Vandoeuvre-les-Nancy F-54506, France 10.3762/bjoc.12.39 Abstract Efficient routes were developed for the diastereoselective synthesis of new O

• derivatives, bearing an arm terminated either with a hydroxy group or a fluorine atom, could be interesting candidates for diastereoisomeric intermediates and biological evaluations, especially for PET imaging experiments. Keywords: C-branched; diastereoselective; fluoroinositols; inositols; O-alkylated

• of inositols. The above results demonstrate that the new O-alkylated and C-branched inositols with myo- and scyllo-configuration were available in a highly diastereoselective way. Different types of arm were easily introduced on the inositol ring. For the O-alkylated series, the hydroxylated (myo-1

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

• simpler variants) [10][11][12]. On the other hand, diastereoselective reactions using at least one chiral component are troublesome. Chiral isocyanides and chiral carboxylic acids invariably afford nearly 1:1 mixtures. α-Chiral aldehydes have a high tendency to racemize/epimerize [13][14] and additionally

• , no report of valuable diastereocontrol by them has appeared so far. Successful examples of diastereoselective Ugi reactions have been reported only with chiral amines [15][16][17][18][19] or with chiral cyclic imines (Ugi–Joullié reaction) [20][21][22][23], although in the latter case, racemization

• , 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

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

• results suggest a contribution of the structural conformation to the diastereoselective outcome of the reaction. Yet, 1,1-disubstituted olefins were not effective, likely due to the increased steric hindrance in the oxygenation step (Table 2, entry 12). Currently, the mechanistic details of this copper