Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• ] were the phosphine boranes were prepared by reacting phosphines with sodium borohydride. Alternatively, the reduction of phosphine oxide byproducts with lithium tetrahydridoaluminate, calcium aluminum hydride, and hydrosilanes can also be used to regenerate the phosphine ligands. Hydrosilane reagents

• usually lead to stereoselective reduction products, hence, they are used for the synthesis of chiral phosphines from chiral oxides [53]. Lithium tetrahydridoaluminate is used for the reduction of achiral phosphines because its action on optically active phosphine oxides leads mainly to the optically

• lithium halogen elimination, halide migration, and ring-opening reactions [56][57]. Butylphosphines are also formed alongside the main product, and in most cases pure phosphine pyridines are obtained using column chromatography followed by extractions adding to the number of synthesis steps. This method

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• , lithium diisopropylamide (LDA)-mediated cyclisation of 2-(methylthio)benzamides, which were obtained by directed ortho-metalation of the respective benzamides followed by quenching with dimethyl disulfide [27] (Supporting Information File 1, Scheme S1). In general, we found the LDA-mediated cyclisation

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the

• lactone 4, which, however, was unstable towards chromatographic purification and used as crude material after lyophilization to remove the solvent. Coupling of 4 with the lithium salt of dimethyl methylphosphonate (5) in THF afforded the β-anomeric ketol phosphonate derivative 6 in 57% yield. The axial

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• stereospecificity make this transformation synthetically appealing [12][13]. Allyl esters of various carboxylic acids undergo rearrangement as their lithium enolates or silyl ketene acetals and the corresponding acids were isolated in 75–80% yields. Accordingly, the Ireland–Claisen rearrangement of lithium enolates

• the corresponding acid 3a in 63% yield at rt (Table 1, entry 1). At a higher temperature, the product yield decreased (Table 1, entry 2). The reaction of the related (E)-but-2-en-1-yl propionate (1b) gave acid 3b under similar conditions with slightly lower yields. The rearrangement of lithium enolate

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.