A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• as starting material reduces the flexibility of this approach. Another strategy introduces the nitrogen at C-2 [11] via the 2-iodoxybenzoic acid-mediated generation of an oxazolidinone ring, selectively leading to C2–C3 syn-products [12]. A third approach features E-selective Julia olefination of (R

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• Reformatsky reaction between L-cysteine-derived thiazolidinic aldehyde 14 and (R)-α-chloroacetyl-2-oxazolidinone 15, leading to the corresponding β-hydroxy amide 16 in both remarkable yield (95%) and diastereoselectivity (>98% de), as shown in Scheme 6. The latter was subsequently converted into the expected

• Isobe et al. for a diastereoselective SmI2-mediated Reformatsky reaction constituting the key step of a highly economical total synthesis of prostaglandin E2 methyl ester [23]. As shown in Scheme 7, the reaction occurred between achiral aldehyde 17 and chiral oxazolidinone 18 in the presence of SmI2 in

• mediate Reformatsky reactions. As an example, chiral oxazolidinone 20 reacted with achiral aldehyde 21 in the presence of SnCl2 to afford the corresponding chiral Reformatsky product 22 as a single diastereomer (>96% de) in moderate yield (56%), as shown in Scheme 8 [24]. The latter was used to synthesize

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• be achieved using an olefination reaction, a metathesis reaction or a copper-mediated reduction of 3,3-difluoropropenes. Pannecoucke’s group employed a chiral auxiliary, the Evans oxazolidinone, to prepare the non-racemic dipeptide isostere 35 (Scheme 7) [34]. Stereoselective alkoxymethylation on the

• oxazolidinone derivative 31 was first achieved with an excellent yield (88%) and diastereoselectivity (de > 95%). The chiral auxiliary was then removed and the free alcohol was oxidized to the corresponding aldehyde 32. Alkene 33 was then obtained after olefination of 32 with low selectivity ((Z):(E) = 64:36

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• , Nakanarusawa 4-12-1, Hitachi 316-8511, Japan 10.3762/bjoc.13.244 Abstract As an extension of the boron enolate-based aldol reactions, the oxazolidinone-installed bisimide 1a from 3-(trifluoromethyl)glutaric acid was employed for Mannich reactions with tosylated imines 2 as electrophiles to successfully obtain

• couple of routes to get successful access to such target molecules with a variety of substituents at the 2-position [1][2][3]. Previously, the oxazolidinone-installed bisimide 1a was employed for the crossed aldol reactions by the way of boron enolate which allowed the isolation of optically active

• , entry 7). Because the employment of the phenylalanine-based oxazolidinone as the chiral auxiliary under the same conditions gave similar results as the one obtained from valine (Table 1, entries 8 vs 7), we decided the conditions in entry 7 (Table 1) as the best of all tested and investigated the

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• . Synthesis of the north-western fragment As shown in Scheme 10, the synthesis of stannane 39 started with aldehyde 48 which was derived from propargyl alcohol in five steps [82]. After DMP oxidation the generated aldehyde 48 underwent a syn-selective Evans aldol addition with oxazolidinone 47 to obtain the

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• became apparent that the reactivity of 12 was more complicated. Running the reaction at 380 °C and 0.3 mL min−1 resulted in 46% of 9 being obtained but, at lower temperatures, different products were obtained. For example, when the reaction was run at 250 °C (Table 4, entry 1), oxazolidinone 13 was

• apparent that the dimer 14 could be formed from oxazolidinone 13 as increasing the residence time led to an increase in selectivity of 14 over 13 (Table 4, entry 2). Indeed, when 13 was used as the starting material, the major product that was isolated was 14; and this reactivity of 13 has been reported

• previously in batch reactions [49]. Increasing the residence time further (Table 4, entry 3) resulted in the oxazolidinone 13 not being detected and 14 was the major product together with a small quantity of mono O-ethylated 14. Reducing the temperature gave a better selectivity to the oxazolidinone 13

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• challenge in the syntheses of glorin and analogs is the differentiation between the α- and the γ-carboxylic acid groups of L-glutamic acid for selective esterification or amidation. α-Selective functionalization was achieved via synthesis of oxazolidinone 6 from Cbz-L-glutamic acid (5) with paraformaldehyde

• and p-toluenesulfonic acid under dehydrating conditions [18]. Opening of the oxazolidinone with sodium ethoxide as nucleophile thus yielded ester 7a, while addition of ethylamine yielded amide 7b. Subsequent amide bond formation with lactam 4 using isobutyl chloroformate or HBTU as coupling reagents

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

• with respect to traditional homogenous systems in terms of milder reaction conditions and easier separation and recycle workups. Two representative examples of ionic liquids employed for the synthesis of FAMEs are the pyridinium and oxazolidinone-based compounds shown in Figure 2 [52][53]. It should be

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• carried out. Crucial steps for the strategy include a Dieckmann cyclization to obtain the 2,3-pyrrolidinedione ring and a Wittig olefination to install the polymethylene chain. An oxazolidinone-containing leopolic acid A analogue was also synthesized. The antibacterial activity showed by both compounds

• the literature [1] (see Supporting Information File 2 for NMR spectra). Interestingly, while searching the best conditions to obtain compound 10, we treated 9 with oxalyl chloride and DMSO, following the Swern protocol [19]. This treatment led to the formation of the oxazolidinone 14 (Scheme 2). We

• assume that the reaction occurred via inversion of the configuration at the hydroxylated carbon, based on an intramolecular SN2 cyclocarbamation by the Boc group [20][21]. The small coupling constant (J = 2.6 Hz) between the two hydrogens on the oxazolidinone ring confirmed that the compound was the anti

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• elements, like a pyrrolidine, a furan-2-one, an oxazolidinone and particularly a 3,4-furylidene moiety in the polyketide part. An analysis of the gene cluster as well as feeding experiments with isotope-labelled precursors led to a proposal for the formation of the furan ring [69][70]. The anticipated

Correction: Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 608–610, doi:10.3762/bjoc.12.59

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• space in terms of a) the isolated and b) the ribosomal bound state. In a first step, an all-atom model of the bacterial ribosome consisting of nearly 1600 atoms was constructed and evaluated. The conformational space of 30 different ribosomal/oxazolidinone complexes was scanned by stochastic methods

• (PRSP) [16]. Nevertheless, though oxazolidinones represent one of the few new chemical classes of antibiotics disclosed in the past 40 years, cases of oxazolidinone-resistant strains have been already reported [17][18][19], underscoring again the urgent demand for new linezolid analogues to overcome the

• pocket for the oxazolidinone ring is characterized by universally conserved 23S-rRNA nucleotides, leading to very similar ligand-bound conformations in different bacterial ribosomes [23]. From a theoretical point of view, the simulation of recognition processes employing nucleotide-based receptors is

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

• -oxazolidinone motifs (Scheme 1D) [16]. Metal-free intermolecular oxyamination reactions have also been accomplished; examples were reported by the Zhu lab with the use of peroxides [17] and by the Studer lab with the use of hypervalent iodo-azide reagents [18]. Furthermore, the intramolecular oxyamination of

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

• construction of the cyclononene unit [49]. The synthesis started with a diastereoselective Evans syn-aldol reaction between substituted propanal 86 and E-crotonyl-oxazolidinone 85 (Scheme 9). The resulting secondary alcohol was silylated and the chiral auxiliary was cleaved with lithium borohydride. Acylation

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• electron-withdrawing group at the quaternary anomeric center decreases the reactivity. In addition, no participating group on C-3 can be used to direct the stereochemistry at the anomeric carbon (C-2) [2]. Efficient chemical sialylation reactions utilize the cyclic 4O,5N-oxazolidinone protecting group [12

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

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• the chiral auxiliary approaches to β-branched arylalanines, including all four stereoisomers of β-methylphenylalanine, the one employing the "Evans amide" method with a 4-benzyl- or 4-phenyl-2-oxazolidinone moiety, has been used most frequently. Along this route, which requires eight procedural steps

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• substrate [36][37]. The activity and enantioselectivity achieved by proline in many cases is thought to be due to a templating effect of the OH group directing the aldehyde in a preferred position via hydrogen bonding [24][25]. It is still controversial whether oxazolidinone formation plays a pivotal role

• in-source fragmentation when slightly harsher ionization conditions are used. This fragmentation is in perfect accordance with the zwitterionic iminium structures II’ and III and can also be rationalized for the oxazolidinone alternative II’’, whereas it requires an additional hydrogen shift from the

• enamine structure II. On the other hand, the comparison with the fragmentation of the structurally related ion [II*b]+ (Figure 5b) is instructive. It doubtlessly possesses an enamine structure since it can neither form a zwitterionic iminium ion nor undergo lactonization to oxazolidinone II’’b because of

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• bearing a chiral oxazolidinone auxiliary, facile access to the cis-aziridine series was possible by using chiral chloroallyl phosphonamide 47a. Thus, the addition of the anion of 47a to tert-butylglyoxylate O-benzylamine (139) led to aziridine 140 as a single diastereomer. Ozonolysis followed by reductive

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• confirmes the stereocenters to have the proposed (2R,3S)-configuration. In their synthesis of (2S,3S)-3-hydroxyleucine, Zhu and co-workers cyclized amino alcohol 5 towards an oxazolidinone, with the carbonyl group simultaneously providing O- and N-protection [32]. Removal of this protecting group required

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• –4:1 syn/anti. The slightly diminished yield of 9c (74–77%) compared to 9a and 9b (85–93%) is rationalized by formation of the oxazolidinone 10c as sideproduct. This cyclic carbamate results from the condensation of the alcoholate moiety of II with the Cbz-function passing the syn-periplanar

• ), Boc2O (1d). Synthesis of hydroxy ketones 7 (R = Me (a), Bn (b), Ph (c) and EtSMe (d); PG = Cbz (a–c), Boc (d)). Synthesis of amides 5e and 5f and ketone 7e. Synthesis of amino alcohols syn-9a–d and oxazolidinone 10a. (for 7a–c conditions A: H2 (1 atm), Pd/C, HCl, MeOH (THF/MeOH 1:1), rt, 3 h; for 7d

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• -component adducts were isolated in good yields up to 92%. A single diastereomer was detected with maleimides; the diastereoselectivity being lower with methyl acrylate and vinyl oxazolidinone (Scheme 7). A one-pot, palladium-mediated cycloisomerization of ene-ynes 5 was applied to the synthesis of the

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions

• Quynh Pham Bao Nguyen and
• Taek Hyeon Kim

Beilstein J. Org. Chem. 2013, 9, 2113–2119, doi:10.3762/bjoc.9.248

• ]. Additionally, in the solid phase asymmetric alkylation reactions, in which Evans' 2-oxazolidinone chiral auxiliaries were used, the yield and stereoselectivity were too dependent on the base, reaction time, and supported resins. As an example, the base-catalyzed epimerization of the chiral center was

• than that in the solution phase (89% de) [27] due to the sterical hindrance of the polymeric support. While the most extensively explored Evans' 2-oxazolidinone chiral auxiliary required a complicated linker [15] and solid supports [14], as well as special treatment, in which the excess base

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• sodium cyanide to afford nitrile 3. Acid hydrolysis of 3 provided the enantiomerically pure carboxylic acid (R)-4 [19], which was then coupled to the oxazolidinone via the mixed anhydride (Scheme 1). With N-acyloxazolidinone 5 in hand, the optically active fluorinated α-amino acids (L-5,5,5

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• preformed organocopper species (Table 2, entries 7–10) [25]. Carbocupration of cyclic N-alkynylcarbamate (chiral oxazolidinone moiety) Recently, our group was particularly interested in the carbometallation reaction of ynamides bearing chiral cyclic carbamates 7, particularly the Evans's oxazolidinone [27

• carbocupration reaction is again at the center of interest but this time for the regioselective addition of organocopper derivatives to various ynamide species. Particularly interesting is the carbocupration of N-alkynyl carbamates 7, bearing Evans’s oxazolidinone chiral auxiliary, which leads to the formation