Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• , geodiamolides and seragamides, is reported. The key step is a Negishi cross coupling of (R)-(3-methoxy-2-methyl-3-oxopropyl)zinc(II) bromide and an (E)-iodoalkene that was synthesized via an aluminium ester enolate attack at (R)-propylene oxide. The overall synthesis comprises nine steps with an overall yield

• assembled by solution-phase synthesis and an open-chain analogue of the natural product was obtained. Keywords: jasplakinolide; marine natural products; Negishi coupling; polyketides; stereoselective synthesis; Introduction Our program on the synthesis of biologically active natural products with peptide

• sp3–sp2 Negishi cross coupling. The required organozinc reagent 8 has been applied occasionally and is accessible from the corresponding commercially available chiral bromide [30][31][32][33][34]. The coupling partner would be an (E)-iodoalkene that was to be constructed from enantiomerically pure (R

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• ) derivatives and dipeptides. In this regard, trimerization and Negishi cross-coupling reactions are used as the key steps starting from readily available 4’-iodoacetophenone and L-serine. These C3-symmetric molecules containing AAA moieties are useful to design new ligands suitable for asymmetric synthesis and

• peptide dendrimers. Keywords: amino acids; cyclotrimerization; Negishi coupling; peptide; Introduction Optically active C3-symmetric molecules are valuable synthons to design dendrimers, chiral ligands, polymers, and supramolecules [1][2][3][4]. In this regard, 1,3,5-triarylbenzene derivatives are

• electroluminescent devices [33]. To address these challenges, we [34] and others [35][36] have synthesized functionalized C3-symmetric molecules containing amino acids and peptides. The Negishi cross coupling [37][38] is a reliable synthetic method, which involves palladium or nickel-catalyzed coupling of organozinc

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• Negishi coupling with aryl bromide, affording the corresponding sterically congested alkene 17b-Ar in 56% yield after two steps. The Negishi coupling with benzyl chloride and the Cu-catalyzed allylation of allyl bromide also afforded the corresponding products 17b-Bn and 17b-Allyl, respectively, in good

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• reactions (e.g., Suzuki–Miyaura, Stille, Kumada, Hiyama or Negishi couplings) play a key role in the preparation of diarylmethanes. However, the reactions involving sulfur-containing moieties have not been reported yet (Scheme 1) [1]. It is noteworthy that under certain conditions, the Pd-catalyzed cross

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

• , oxidation of the secondary alcohol with pyridinium dichromate into the corresponding cyclopentanone derivative and subsequent olefination using CBr3F gave the monofluoroalkene 96 with a modest selectivity towards the (Z)-alkene. A Negishi coupling then gave alkene 98. Stereoselective reductive amination

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ; palladium; silicon; Introduction The development of transition metal-catalyzed cross-coupling technologies over the last four decades revolutionized the synthetic chemistry. Indeed, the importance of Pd-catalyzed coupling was recognized with the 2010 Nobel Prize awarded to Heck, Negishi and Suzuki [1][2

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• reported by the groups of Kishi, Negishi, Burkart, Altmann, Aggarwal, Gurjar, Feringa, Minnaard, Blanchard and Dai will be discussed. As a consequence of the enormous amount of work published in the field, not every single aspect of this research can be covered. While trying to be as comprehensive as

• principal approaches have been used to establish the 12-membered macrolactone ring, namely (1) ring-closure by macrolactonization, the approach followed by Kishi, Negishi and Aggarwal, or (2) ring-closing olefin metathesis (RCM) to form the C8–C9 double bond, which is part of Burkart’s and Altmann’s

• ], published in 2007, Kishi and co-workers increased the overall efficiency of the synthesis by reorganizing the assembly of the principal fragments and by optimizing the key C(sp2)–C(sp3) Negishi cross-coupling reactions as well as the choice of protecting groups. The 3rd generation approach [123], published

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• species with ZnCl2 should lead to at C-1 zincated isoquinolines, which could undergo Negishi cross-coupling reactions with appropriately substituted methyl 2-bromobenzoates to give methyl 2-(isoquinolin-1-yl)benzoates. These would again open an access to oxoisoaporphine alkaloids via intramolecular

• extended to 6-methoxyisoquinoline (7c). Unfortunately, transmetalation with ZnCl2 at 0 °C followed by palladium-catalyzed (5 mol % Pd(dba)2/ 10 mol % P(2-furyl)3 or 1 mol % Pd2(dba)3/2 mol % RuPhos) Negishi cross-coupling reaction with methyl 2-bromo-5-methoxybenzoate did not lead to the expected methyl 2

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• the neat synthesis of GE2270 central core in 33% yield over a 4-step sequence (Figure 1) including three Negishi and Stille cross-coupling reactions to achieve the direct introduction of mono- and dithiazolyl units to a 2,3,6-trihalopyridine [17]. The strategy has then extended to the total synthesis

• of thiopeptides GE2270 in which the macrocylization and heterocyclic core was simultaneously achieved through a late-stage Negishi cross-coupling [18][19]. Last year, Yamaguchi’s group proposed a novel elegant [4 + 2] cycloaddition Kondrat’eva reaction between a 2-alkenylated thiazole-4-carboxylate

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• Negishi cross-coupling of arylzinc with protected glycosyl bromide in the presence of Ni-catalysts. An improved procedure with high stereoselectivity and in the absence of catalysts was reported subsequently by Lemarie et al. (Scheme 1) [12] to construct the anomeric chiral center of dapagliflozin and

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• synthesis of seleno-functionalized heterocycles [20][21]. Recently, the use of alkynyl selenides as substrates for Pd-catalyzed Suzuki, Negishi, Kumada and Sonogashira cross-coupling reactions has been reported with good yields [22]. Due to the synthetic relevance of alkynyl selenides several methodologies

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd

• condensation product was confirmed by crystal structure analysis. Keywords: Negishi coupling; NMR (1H; 13C; 15N); pyrazole; pyridine; X-ray structure analysis; Introduction The pyrazole nucleus is a frequently occurring motif in many pharmaceuticals [1][2] and biologically active compounds [3][4

• -diketones with arylhydrazines, halogenation of the resulting 1,3,5-triarylpyrazoles in the 4-position and further functionalization via Negishi cross-coupling [23][24] or halogen–lithium exchange reaction (Scheme 1). The resulting compounds amongst others seem to be interesting as potential complexing

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• telescoped homocatalysis procedure consisting of a three-step sequence (metalation, zincation and Negishi cross-coupling) which furnishes an easy access to a variety of functionalized 2-fluorobiaryl and heteroaryl products (Scheme 9) [59]. This strategy is rightfully considered green because it guarantees

• products. Experimental setup for the flow synthesis of 2-fluorobi(hetero)aryls by directed lithiation, zincation, and Negishi cross-coupling. (Adapted with permission from [53], copyright 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim). Experimental setup for the coupling of fluoro-substituted pyridines

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• diesters: In 1951, Gilmore has demonstrated that use of esters, rather than free arylpropionic acids in phosphoric acid, in the presence of phosphorus pentoxide also led to 1-indanones in equally good or even better yields [32]. Transition metal complexes have been used by Negishi et al. as catalysts in

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

• carboxylic acid [50][51]. In 2011, the Donohoe group developed a total synthesis of neodysiherbaine A (14) using an Os(VI)-catalyzed type B oxidative cyclization of a 5,6-dihydroxyalkene (Scheme 5, right) [52]. Commercially available β-D-ribopyranose tetraacetate (11) was converted to 12 via a Negishi

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• -dibromobenzofuran with arylboronic acids under palladium catalyzed conditions [29][30]. Bach et al. reported site-selective studies involving the Sonogashira, Negishi, Kumada cross-couplings employing 2,3-dibromobenzofuran and 2,3,5-tribromobenzofuran substrates [31][32][33]. Additionally, Langer et al. reported

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• leading to a number of different 2,4- and 2,5-diaryldimethylpyridines P3, P4 [25], 4-benzylpyrimidines P2 [26], and 4-methyl-5-arylpyrimidines P1 [26] was needed. For this purpose, we successfully used Suzuki and Negishi cross-coupling reactions between arylboronic acids/benzylzinc reagents and

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

• ]. This simple and effective diamine-free procedure allowed the reaction to take place at −30 °C, which is more desirable than −78 °C in process chemistry. Under the new reaction conditions, electrophiles such as TMSCl, MeO2CCl, DMF, Ph2CO, and PhBr (via a Negishi coupling process) can be used to install

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• successfully performed in six steps with an overall yield of 6.5%. The steps included an organometallic intermediate and a Negishi cross-coupling reaction characterized by a transmetalation with zinc and palladium. The benzonaphthyridinone product was transformed into a bromobenzonaphthyridine intermediate by

• using phosphoryl bromide. Another organozinc substrate was coupled to the obtained intermediate by a Negishi cross-coupling and cyclisation occurred to give the expected secondary metabolite (Scheme 8) [68]. The yield of the last step in the preparation of 9 could be improved by using the synthetic

• h. Therefore, the second Negishi coupling needed to be performed with N,N-dimethylnicotinamidezinc chloride. Synthesis of pyridoacridine analogues The strong antiproliferative activities shown by these alkaloids inspired the design and the synthesis of many pyridoacridines analogues. Scheme 9 shows

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

• -ferrocenediyl)-1,1,2,2,3,3,4-heptafluorobutane. The authors have reported a [2 + 2] cycloaddition reaction under thermal conditions. 1,10-Bis(trifluorovinyl)ferrocene (261) was synthesized starting with diiodoferrocene 260 by Negishi-type coupling. Compound 261 was subjected to a [2 + 2] cycloaddition sequence

Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

• Christian Benkhäuser and
• Arne Lützen

Beilstein J. Org. Chem. 2015, 11, 693–700, doi:10.3762/bjoc.11.79

• (trimethylsilyl)acetylene into 7 in a yield of 85% [27]. Alkyne 7 was then subjected to a Negishi reaction with 2-bromopyridine (8) derived zinc organyl 9 to give the silyl-protected ethynylated bipyridine 10 in excellent yield of 99% which was subsequently desilylated under standard conditions to give terminal

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

• Fatma Belkessam,
• Aidene Mohand,
• Jean-François Soulé,
• Abdelhamid Elias and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 2912–2919, doi:10.3762/bjoc.10.309

• semiconductors [2]. Due to these multiple uses, the discovery of a simpler access to terthiophene derivatives would be very useful. Suzuki, Stille or Negishi Pd-catalyzed cross-coupling reactions represent some of the most efficient methods for the preparation of 2,5-diheteroarylated thiophenes [3][4][5][6][7][8

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• variety of arylated thiophenes. For such coupling reactions, the major byproduct is a base associated to HX, instead of metallic salts which are produced under the more classical Negishi, Suzuki or Stille cross-coupling reactions. Moreover, direct arylation avoids the preliminary preparation of

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• started from 1-bromo-4-methoxybenzene which was transferred into 2-bromo-4’-methoxybiphenyl (3) in 92% yield via lithiation with t-BuLi, transmetallation with zinc(II) bromide, and subsequent Negishi cross-coupling reaction with 1-bromo-2-iodobenzene [14][15]. 3 was then transformed into the corresponding

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• -coupling reaction in excellent yields [26]. The non-symmetric 4,6’-disubstituted bipyridine 10 was obtained in good yield from a Negishi cross-coupling of 6 and 7 [27]. Cleavage of the pyrrole protecting groups of 8–10 with hydroxylamine provided the corresponding diamines 11–13 [26] in satisfying to