The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• -threonine in the third position. Both N-Boc protected (compounds 1a–4a) and N-deprotected pentapeptides (1b–4b) were studied. Results and Discussion Synthesis. First, we synthesized the two (2S,3R)- and (2S,3S)-CF3-Thr analogues. An enantioselective synthesis of (2S,3R)-Boc-CF3-Thr was proposed in 2003 [16

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• –71%, respectively (Scheme 29) [42]. An interesting example of the application of ylides derived from vinylphosphonium salts in the enantioselective synthesis of pyran derivatives was reported by Ley et al. in 2010. β-Hydroxyaldehyde 43 as the oxygen nucleophile was obtained here in the asymmetric

• presence of sodium hydride. Synthesis of 2H-chromene and 2,5-dihydrofuran derivatives in the intramolecular Wittig reaction with the use of vinylphosphonium salts and an appropriate oxygen nucleophile containing a carbonyl group. Enantioselective synthesis of 3,6-dihydropyran derivatives from

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

• incorporated into peptides, it is normally necessary to first synthesize a dipeptide where the amide bond has been replaced with a monofluoroalkene. In that context, this review will present the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres described since 2007. Some

• will discuss the new developments on the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres from 2008 to September 2017. First, synthetic approaches to analogues in which there is no side chain or where the side chain stereochemistry is not controlled will be

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• transformations [14][15][16][17]. One of the major applications of organocatalysis lies in the field of enantioselective synthesis, where organocatalysts are considered as fundamental tools in the catalysis toolbox [18][19][20][21][22]. Moreover, the reactivity and selectivity of organocatalysts can be further

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• functional groups in a chiral molecular skeleton were applied to the enantioselective synthesis of axially chiral benzamides via aromatic electrophilic bromination. The results demonstrate the versatility of bifunctional organocatalysts for the enantioselective construction of axially chiral compounds

• axial chirality [36][37]. Thus, we assumed that this method could be further applied to the enantioselective synthesis of a range of axially chiral compounds. In this study, we present the enantioselective synthesis of 3-hydroxybenzamides via aromatic electrophilic bromination [28][29]. The 3

• activation involving the phenolic hydroxy group. Conclusion In summary, we demonstrated a novel enantioselective synthesis of axially chiral benzamides, using bifunctional organocatalysts, via aromatic electrophilic halogenation. Moderate to good enantioselectiveties were accomplished with various benzamide

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• natural products. Construction of spirocyclopentaneoxindole scaffolds. Scope of enantioselective synthesis of spirooxindoles. Reaction conditions: catalyst d (0.01 mmol), oxindoles 1a–o (0.11 mmol) and nitroolefins 2a–c (0.1 mmol) in CH2Cl2 (3 mL), method A or method B. The ee values were determined by

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• aldehydes to nitroolefins and enantioselectivities up to 85% ee were achieved. Keywords: enantioselective synthesis; Michael addition; organocatalysis; pyrrolidines; synthetic methods; Introduction In the first decades of the 21st century, the enantioselective organocatalysis has witnessed a tremendous

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

• converted to enantiomerically pure (+)-eurylene (87) (Scheme 18). The Brown group published an enantioselective synthesis of the cis- and trans-THF fragments of eurylene (87) in 2010 [155] using an auxiliary controlled Mn(VII)-promoted oxidative cyclization to form THFs 90 and 93 (Scheme 19). Both THF

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• protected peroxide 259. The subsequent triethylamine-catalyzed rearrangement of 259 leads to protected intermediate 260 the treatment of which under acidic conditions afforded hydroperoxide 254 in 70% yield (Scheme 80). One approach to the enantioselective synthesis of 4-hydroxyenones 262 is based on the

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• enantioselective synthesis of β-amino esters 62 via the addition of arylboronic acids 47 to α-methylaminoacrylates 61 (Scheme 14) [35]. The authors identified (S)-difluorphos (44, Figure 2) and phthalimide as the optimal ligand and proton source combination, respectively. Additionally, the bulky tert-butyl ester

• Genet’s addition of potassium organotrifluoroborates to α-aminoacrylates. Proposed mechanism for enantioselective additions to α-aminoacrylates. Sibi’s addition of arylboronic acids to α-methylaminoacrylates. Frost’s enantioselective synthesis of α,α-dibenzylacetates 64. Rovis’s hydroheteroarylation of α

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

• . Inspired by the biological potential and synthetic utility, metal- or organo-catalyzed asymmetric synthesis of chiral 3-hydroxyoxindoles have been highly pursued in the last decades. An excellent review by Chimni and co-workers summarized the catalytic strategies for the enantioselective synthesis of

• the aldolization step can be carried out on a multigram scale. Very recently, Tsogoeva and co-workers reported the amino alcohol-catalyzed one-pot enantioselective synthesis of antileukaemia agent (R)-convolutamydine A in 95% yield and with 85% ee under mild conditions (Scheme 23) [39]. Notably, the

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

• carbon-substituted piperazines [19][20][21][22]. Mendoza et al. have developed a [3 + 3] dimerization of azomethine to synthesize highly substituted piperazines [23]. Notably, Stoltz and co-workers recently developed an enantioselective synthesis of piperazin-2-ones and piperazines using a palladium

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

• have exhibited efficient catalytic activity in the asymmetric Mannich reaction. In fact, the use of simple trans-(1R,2R)-aminoindanol (1c) as an efficient organocatalyst in the enantioselective synthesis of natural products as the TMC-954 core [12][13], has been recently reported. These examples show

• substituted product 14. Reaction pathway proposed for the preparation of the compounds 14. The enantioselective synthesis of cis-vicinal-substituted indane scaffolds 21, catalyzed by ent-6. Asymmetric domino procedure (Michael addition/Henry cyclization), catalyzed by the thioamide ent-6 which involves a cis

(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

• enantioselective synthesis of α,α-disubstituted cycloalkanones 10. Starting from α-substituted cycloalkanones 8 and alkenes 9, containing an electron withdrawing group, α,α-disubstituted cycloalkanones were obtained (Scheme 7) [18]. The reaction described above provided products with yields up to 96%, ee up to 98

• 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

• either of the nitro group or the thioether group. The same year Wang and co-workers reported the enantioselective synthesis of spiro-chromanone-thiochroman compounds 175 catalyzed by a bifunctional indane-based thiourea 176 (Scheme 57) [78]. The cascade is initiated by the sulfa-Michael addition of 2

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

• -dimethylbutyrate. In this reaction, only one diastereoisomer was formed during the Ullmann coupling and the auxiliary is easily prepared and removed by hydrolysis after the coupling reaction (Scheme 3). In 2007, Breit et al. [22] employed a chiral tether to link two aryl halides for the enantioselective synthesis

• )hexopyranose derivatives. Preparation of 3,3’-disubstituted MeO-BIPHEP derivatives. Enantioselective synthesis of trans-4,5,9,10-tetrahydroxy-9,10-dihydrophenanthrene. Copper-catalyzed coupling of oxazoline-substituted aromatics to afford biaryl products with high diastereomeric purity. Total synthesis of O

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• centres (Scheme 41). Sakurai and co-workers have successfully established an enantioselective synthesis of the C3-symmetric chiral trimethylsumanene through a Pd-catalyzed cyclotrimerization and the RRM protocol as key steps [45]. Here compound 207 reacted with catalyst 1 in the presence of ethylene (24

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• pharmacological tests for antidepresant activity [1][2][3], it is still administered as a racemate probably due to the fact that no serious adverse effects have been recorded for the (R)-enantiomer. Interestingly, no enantioselective synthesis of mianserin has been developed so far. The synthesis of racemic

• auxiliary was described by the Czarnocki group [7]. For the commercial manufacture of mianserin enantiomers both the above mentioned processes are rather unjustified economically and the most advantageous method could be the enantioselective synthesis. Considering our experience in asymmetric synthesis of

• more active form [9]. In a key step in the enantioselective synthesis of mianserin and epinastine we applied the asymmetric reduction of the prochiral imine by asymmetric hydrogen transfer reaction (ATH) [10][11][12][13][14]. The proposed strategy could be used for the preparation of the title

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , Shair and co-workers [196] have reported the enantioselective synthesis of (−)-longithorone A by using a conventional synthesis to realize the proposed biosynthesis, which was put forward by Schmitz involving an intermolecular and an intramolecular DA reaction of two [12]paracyclophanequinone [197

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

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

• oxidation used in the preparation of the poison frog alkaloid 195C [80]. Preparation of iminosugars using an electrochemical approach [81]. The electrosynthetic preparation of α-L-fucosidase inhibitors [84][85]. Enantioselective synthesis of the anaesthetic ropivacaine 85 [71]. The preparation of

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• straightforward approach for the preparation of optically active promethazine and ethopropazine molecules, respectively. Results and Discussion Herein, we wish to present an original chemoenzymatic procedure for the enantioselective synthesis of promethazine 9 and ethopropazine 10. Most of our efforts during

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• enantioselective synthesis of the (4aS,8aR,8S)-hydrolilolidone core 37 [63][64] present in aspidospermine (36), and thus a formal total synthesis of the alkaloid itself, intercepting Stork’s classic route [61]. One precursor described in the core synthesis is enone 38, which bears the quaternary stereocenter 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

• , respectively, and subsequent conversion of the primary adducts [35]. The enantioselective synthesis of α-phosphonosulfonic acids as squalene inhibitors, as discussed later in this review, was achieved using similar reactions – asymmetric alkylation of an α-sulfo phosphonamide and asymmetric α-sulfuration of an

• converted exclusively into various sterols, such as cholesterol, by a multi-step pathway [78]. The α-phosphono sulfonate 19 was found to be a potent inhibitor of squalene synthase, however, only the racemic version was originally tested. Biller and co-workers designed an enantioselective synthesis of 19

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• diastereoselectivity [36], but since initially we did not require an enantioselective synthesis and the Zhou method employed rather expensive reagents, we investigated a simpler and cheaper route to access both cis- and trans-isomers. We envisioned a stereoselective synthesis that would potentially allow for the

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106