N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• (2S,1'S)-6 correspond to (S)- or ʟ-serinal (Figure 3) [13]. Furthermore, since the aziridine ring openings can be accomplished with other nucleophiles and the reductive cleavage is also known [14][15] the aziridines 5–8 offer a plethora of opportunities for enantioselective synthesis of structurally

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• roots of Parthenium hysterophorus [5]. A recent enantioselective synthesis of (−)-isoguaiene (1) from (+)-dihydrocarvone [6] enabled an unambiguous assignment of its absolute configuration as depicted in Figure 1. Due to the structural similarity of 1 and the trisnorsesquiterpene clavukerin A (2), we

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• when the same sequence of diastereoselective carbometalation/oxidation was performed on cyclopropenyl ester 1, the in situ-formed donor–acceptor cyclopropanol undergoes a selective ring-opening to provide the acyclic product possessing a quaternary carbon stereocenter [57]. As the enantioselective

• synthesis of the cyclopropenylmethyl ether 3 was easily achieved in high enantiomeric ratio (er 93:7, Scheme 5 [78][81][82]), the subsequent combined diastereoselective carbometalation reaction and oxidation gave the enantiomerically enriched cyclopropanols 5 as unique diastereoisomer with the same

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• and inexpensive synthesis of HPA-12 was felt. Our own interest in developing anticancer agents also prompted us to develop a new and practical enantioselective synthesis of 2 [26][27][28][29]. To realize our objective, we paid particular attention to obtain 2 using reactions that are high-yielding and

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• ][6]. Notably, organofluorine compounds bearing a tetrafluoroethylene (–CF2CF2–) unit have attracted significant interest as a promising framework for various functional molecules. In the medicinal field, for example, Linclau and co-workers reported the first enantioselective synthesis and the

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• precatalyst in iodine(III)-catalyzed enantioselective synthesis of spiroketals with high selectivities. In this report, substrates 128 were reacted with 10 mol % of chiral iodoarene 129a and 129b in the presence of mCPBA oxidant in chloroform at 0 °C. The desired ortho-spirocyclic ketals 130 were obtained in

• chiral auxiliaries 129a or 129b under similar reaction conditions mentioned in Scheme 48. Furthermore, the synthesized spiroketal 159 (R2 = iPr; R4 = SiMe3) was used as synthetic intermediate for enantioselective synthesis of natural product (−)-biscarvacrol [8] (Scheme 59). Additionally, Parra and

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• the organic phase. Due to the sterical hindrance from the benzyl group, the alkylation by 1,5-dibromopentane takes place at the opposite side of the benzyl group of C7 to afford 3a. Conclusion In summary, an enantioselective synthesis of (R)-(+)-1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone (3a), a

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• )-isomer. Keywords: 1,2-difunctionalization of alkenes; enantioselective synthesis; hypervalent iodine; oxidation; Findings Hypervalent aryl-λ3-iodanes have been widely used for metal-free oxidation with high selectivity in organic synthesis [1][2][3]. The reactivity of an aryl-λ3-iodane is controlled by

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• natural product is 6-nonyl-2H-pyran-2-one. The antimicrobial and cytotoxic effects of the synthetic volatiles are also reported. Keywords: enantioselective synthesis; gas chromatography; mass spectrometry; natural products; volatiles; Introduction A large variety of volatile organic compounds from

• 11 were separable by GC on a homochiral stationary phase, one of which matched the natural product in terms of same retention times and mass spectra (Figure 3). To clarify the relative and absolute configuration of the natural stereoisomer of 11 an enantioselective synthesis was performed (Scheme 5

• unfortunately not of 11c. However, as described above, enantiomerically pure (4R,5S,6S)-11c was obtained by enantioselective synthesis, and the peaks for the enantiomers of 11c in the GC analysis on a homochiral stationary phase could be readily assigned by comparison to synthetic (4R,5S,6S)-11c. Finally, a

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