A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• (and nitrile) were necessary to drive the reactions to completion as the acylated product is more acidic than the nitrile starting material. More recently, ester or Weinreb amide reactions with acetonitrile using lithium bases at low temperature [7], or similarly NaH at high temperatures [8], have been

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• -ᴅ-Ala (16) was coupled to O-benzylserine ethyl ester 37 to give dipeptide 38, hydrogenolytic debenzylation gave the substrate 39 for the copper(I)-mediated elimination of the carbodiimide formed in situ using EDC, and then yielded the dipeptide Boc-ᴅ-Ala-Dha ester 40 in good yields. Lithium

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• added the double Grignard reagent 4 to methyl esters 5 [26]. A similar approach was established by Lavis, herein electrophiles (anhydrides or esters) were added to lithium or magnesium organyls 4 [27]. Johnsson and co-workers could establish dye formation by addition of aryllithium 7 to the silicon

• xanthone 6 [8]. A related strategy, adding lithium compound 7 to a preformed tricyclic system 8, was used by Nagano et al. to synthesize the Ge and Sn rhodamine analogues [14]. In a recent publication, Urano et al. synthesized the rhodamines 13–15 by coupling the triflate of xanthone 12 with boroxines 9b

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• synthesis of dithienylethene fluorescence reporter Glyco-DTE is shown in Scheme 2. The dithienylethene derivative 3 was prepared by Suzuki coupling of dithienylethene 1 with methyl 4-bromobenzoate followed by hydrolysis with lithium hydroxide. The naphthalimide fluorophore 6 was synthesized through bromide

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• )lithium reacts again with starting material 19 resulting, after several steps (the so called halogen dance), in the lithiated pyridine intermediate 18 that can add to the silicon xanthone 17. Low temperatures for the HD reaction are required when more equivalents of the base are used to maintain a

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• –nitrogen double bond [13] (see Figure 2B), further undesired bromo–lithium exchange is possible at C-4. Since halogen substituents at C-4 are further readily substituted by nucleophiles, we considered bulky, non-nucleophilic amide bases as most promising for the metalation at C-5. Inspired by reports of

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• Sodeoka [40] reported the first example of an enantioselective monofluorination of α-keto esters catalyzed by Pd-μ-hydroxo complexes with cyclopentyl methyl ether (CPME) as the best solvent (Scheme 6). Also, they achieved the diastereoselective reduction of the remaining keto group with lithium tri(sec

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• butenolide 70. The second one is the reaction of alicyclic alcohol 73 with dimethylformamide dimethylacetal to give an allylic amide by means of a [2,3]-sigmatropic rearrangement of a carbene intermediate. Epoxidation the allylic amide with m-CPBA gave 74, followed by lithium hexamethyldisilazide-induced β

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• reduced further by choosing M to be potassium rather than lithium; as an added benefit, the resulting potassium halides are less likely to contaminate the desired product. Without a solvent present and if M and M' are both univalent metals with similar electronegativity, complete exchange becomes

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• presence of sodium hydride. Helic[6]arene derivative H5 was synthesized by treatment of H1 with methyl bromoacetate followed by reduction with lithium aluminium hydride (Scheme 1). The guests G1–3 were prepared according to previously reported procedures [37][38][39]. Guest G4 was synthesized through

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• isomeric mixture of esters 16. Subsequent reduction with lithium aluminum hydride gave a mixture of alcohols 17 and 18, which could be readily separated by silica gel chromatography. The assignment of stereochemistry of these isomers was based on shielding effects in both 1H and 13C NMR spectra. For

• trifluoromethyl-substituted cyclopropylcarbinyl systems were prepared by addition of the carbene derived from the diazoester 56 to vinyltrimethylsilane as shown in Scheme 12. Reduction of the ester mixture 57 with lithium aluminum hydride gave a chromatographically separable mixture of alcohols 58 and 59

• CF3 group is trans to the TMS group in the isomer 59. Additional cyclopropylcarbinyl systems containing the electron-withdrawing cyano and carbomethoxy groups were prepared in an analogous fashion as shown in Scheme 13. Carbomethoxycyano carbene addition to vinyltrimethylsilane followed by lithium

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

• lithium enolate of methyl 4-methoxyphenylacetate would give the β-hydroxyester 169 which when treated with Lewis acid experienced the aziridine ring cleavage with simultaneous dihydrofuran-2-one ring closure to produce 170 contaminated with small amounts of the corresponding furan-2(5H)-one 171

• salts in a similar way [33]. However, to introduce the hydroxy group at C3 of the piperidine ring addition of a lithium acetylide to the aziridine aldehyde (2S,1'R)-6 was performed (Scheme 51) instead of alkylation (Scheme 50). Two diastereoisomeric acetylenic alcohols were formed in the reaction with

• lithium ethyl propiolate in an 8:2 ratio, and the major product 191 had the required configuration. After protection of the hydroxy group in 191 Weinreb amide 192 was prepared to facilitate the installation of the respective alkyl chains in ketones 193a and 193b. They were transformed into

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• allyldioxazaborolidine 11), respectively. The tetronate building blocks 4 and 5 were further converted to the corresponding enolates using lithium diisopropylamide and allowed to react with the common key intermediate 3 to afford the hydroxyalkylated products 18 and 19, in 78% and 59% yield, respectively (Scheme 4

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• rearrangement of the so-formed alkynyloxiranyl borates. This stereospecific process overall transfers the cis or trans-stereochemistry of the starting alkynyloxiranes to the resulting 1,3-enynes. Keywords: boron; enyne; lithium; oxirane; rearrangement; Introduction Lithiated oxiranes are useful intermediates

• lithium observed by X-ray diffraction in the lithiated o-trifluoromethylstyrene oxide [37] may be further elongated due to hindrance introduced by the trans-substituent adjacent to the lithium atom of the second oxirane in the dimer (Scheme 2, entry 5). Such effect may facilitate the formation of the

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• lithium ion) that dissipate all their energy in a path of the order of a cell diameter (5–9 μm) in biological tissues, which gives them the potential for precise cell damage. Highly selective delivery, accumulation of boron in tumor tissues and proper subcellular distribution are required to achieve a

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• pseudoaxial methyl of the gem-dimethyl group [18][24]; it was proposed that the axial methyl group directed electrophile incorporation away from itself (Scheme 4). The fragile nature of the lithium ester enolate of dimethyl tartrate acetonide (to β-elimination with loss of acetone) was evident from Seebach’s

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• appended. Unfortunately, reactions of 6 and 8 utilizing catalytic hydrogenation, lithium aluminium hydride by itself as well as with added aluminium chloride or samarium iodide produced only trace amounts of an amine (e.g., 9). When samarium iodide was used as the reagent, the only discernible product (not

• , followed by addition of bromide 5a, potassium phosphate and PdCl2(dppf)2 in DMF at 85 °C for 3.5 h gave the coupled product 10 in 47–63% yields (Scheme 3). In contrast to the case of the Heck coupling products (6 and 8, Scheme 2), nitrile 10 underwent facile reduction with lithium aluminium hydride. The

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• removing the chiral-resolving menthyl substituent with lithium aluminium hydride (LAH), the enantioselectivity of (R)-d was higher than 99% ee when checked with HPLC (Supporting Information File 1, Figure S3). Catalyst 4 was then obtained by homo-coupling of (R)-d with Ni(PPh3)3Br2/Zn with 37% yield. The

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• deprotection agent was tested, trimethylsilyl iodide, as it was recently published by Danjou et al. [24] as a removal agent of methoxy groups on calixarenes architectures. Although we succeeded with the removal of methoxy groups, both aldehydes were reduced. Furthermore, the lithium chloride/N,N

• -dimethylformamide system was tested according to the study of Fang et al. [25] revealing that the methoxy group in the meta-position of an electron-withdrawing substituents can be removed under microwave irradiation. However, when testing the system on 5b, no reaction occurred. Another experiment with lithium

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• NHPI-catalyzed C–H acetoxylation reaction yielded the ester product 3a in moderate (42%) yield. This contrasts with orthoperiodic acid (H5IO6), which yielded only electrophilic arene iodination. The use of alkali metal iodate salts such as lithium, sodium, and potassium iodate as the terminal oxidant

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• min, 95%; c) i. DBU, DCM, rt, 1 d; ii. TBAF, THF, 0 °C, 10 min, 87% (over two steps). LDA = lithium diisopropylamide, HMPA = hexamethylphosphoramide, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, TESCl = triethylsilyl chloride. Supporting Information Supporting Information File 206: Experimental part.

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• of a chiral auxiliary with lithium dibutylcuprate. Next, titanium tetrachloride-catalyzed cyanation secured another carboxy group and after a few transformations an oxazolidinone (4S,5R)-39 was obtained as a major (7:1) product readily purified chromatographically. To complete the synthesis of (2S,3R

• electrophilic hydroxylation at C4 When the lithium enolate of dimethyl N-Cbz-L-glutamate 63 was treated with Davis oxaziridine, an inseparable 9:1 mixture of diastereoisomers was formed with (2S,4S)-64 predominating (Scheme 16) [74]. For sodium and potassium enolates diastereoselectivity of the hydroxylation

• [86][87][88] or a Diels–Alder reaction using acylnitroso compounds [89]. However, when compared with these multistep approaches hydroxylation of pyroglutamic acid derivatives seems to be the simplest option. Treatment of the lithium enolate of benzyl N-Boc-pyroglutamate (S)-86 with Davis oxaziridine

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• (RCM) of dialkenes, ring-opening metathesis polymerisation (ROMP), isomerisation of alkenes and cross-metathesis (CM) of alkenes [7]. The complexes were synthesized by reacting the lithium salts of the corresponding pyridinyl alcohols with [RuCl2(=CHC6H5)(P(iPr3))2]. These complexes catalysed inter

• with GxF/0.45 µm GHP membrane (PALL) was used to filter the lithium salt from the precatalyst. Experimental procedures Precatalyst synthesis: The well-established methods of Herrmann et al. [23] and Van Der Schaaf et al. [7] were used to synthesize precatalysts 6–9. This is illustrated in Scheme 2

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• PQS such as formylation followed by oxidation failed when applied to OMe-HHQ (3). Alternatively, ortho-metalation next to the methoxy group of OMe-HHQ (3) followed by borylation/oxidation was investigated. Several trials using different lithium bases failed and only small amounts of oxidation products

• in the benzylic position could be observed. Instead of direct ortho-metalation, a strategy based on halogen–lithium exchange proved to be more suitable. To this end, HHQ (1) was converted into 3I-HHQ (8) following a literature procedure [21]. 3I-HHQ (8) was then methylated using the MeI/K2CO3

• hand, the halogen-lithium exchange was attempted. Treatment of 9 with n-butyllithium at −78 °C followed by the addition of B(OMe)3 and finally in situ oxidation using sodium perborate provided the desired 4OMe-PQS derivative 11 in moderate yield (35%, Scheme 3). The same procedure could be applied to

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• previous study was 3 MPa [27], 5 MPa CO2 was applied in the present study to promote a higher consumption of LO. The result showed the isolated yields were improved to 84% yield for 1a and 30% yield for 1d. In our previous report, 1d was reduced by lithium aluminium hydride (LAH) to obtain the