Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• stereoisomer analogues of RvD2 (1). Removal of the TIPS group with TBAF gave terminal alkyne 12. Alkyne 12 then underwent smooth hydrozirconation utilizing the procedure reported by Negishi [24] were ZrCp2HCl is generated in situ by reduction of ZrCp2Cl2 with DIBALH in THF. Iodinolysis of the zirconium species

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• investigated by Negishi for the hydrozirconation–transmetallation process [80]. Our findings were in agreement with the results of Murakami. High syn-selectivity (>1:20 anti/syn) was achieved in CH2Cl2 with Et2Zn as the transmetallating agent. The reaction could also be performed in toluene, but the

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• recently reported an approach to forming the first aryl–aryl C–C bond by a directed lithiation of a pyridine 1.91 followed by conversion to its organozinc derivative. This intermediate then undergoes a high-yielding Negishi cross-coupling reaction with an arylbromide (Scheme 17) [52]. After acidic

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• uncatalyzed carbomagnesiation (Scheme 5) [60][61]. This addition proceeded in an anti fashion to give intermediate 2a. The trend is the same in copper-catalyzed reactions of wide scope [62]. In 2001, Negishi applied copper-catalyzed allylmagnesiation to the total synthesis of (Z)-γ-bisabolene (Scheme 6) [63

• forming alkylated products (Scheme 31) [105]. As shown in Scheme 32, carbomagnesiation of dialkylacetylene provided the corresponding arylated product only in low yield. Although Negishi reported ethylzincation [106], allylzincation [107], and methylalumination [108] with a stoichiometric amount of

• 2000, Negishi reported zirconium-catalyzed ethylzincation of 1-decene to provide dialkylzinc intermediate 4h (Scheme 41) [123]. Intermediate 4h reacted with iodine to provide alkyl iodide 4i in 90% yield. The carbozincation reaction is cleaner and affords the corresponding products in high yields

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• isolated in modest yields (30–33%), even in the presence of additional HMPA, which might may constitute the major limitation of our process. Other attempts involving electrophiles such as acid chlorides and allyl bromide or transmetallation with zinc chloride and Negishi cross-coupling were unsuccessful

Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

• Andreas Unsinn,
• Cora Dunst and
• Paul Knochel

Beilstein J. Org. Chem. 2012, 8, 2202–2206, doi:10.3762/bjoc.8.248

• 9 in 77% yield. Direct Pd-catalyzed Negishi cross-coupling [24][25][26][27][28] of 9 with an arylzinc derivative failed. However, the bromide 9 could be readily converted to the corresponding iodide 10 by a bromine–magnesium exchange using iPrMgCl·LiCl [29][30][31][32][33][34][35] followed by

• iodolysis leading to the iodide 10 in 93% yield. Treatment of 1,2-dibromobenzene with iPrMgCl·LiCl at −15 °C for 2 h followed by a transmetalation with ZnCl2 gives the required zinc reagent 11, which undergoes a Negishi cross-coupling with the iodide 10 at 50 °C (5 h) leading to the alkynyl thioether 1a in

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• . Metalation of 27 with n-butyllithium provided the allenyllithium reagent 28 next, which was subsequently converted into the organozinc reagent 29. In a Negishi-type coupling of this intermediate with either the bromoallene 30 or its deuterated version 27 the two target compounds were obtained in the final

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• and Heck reactions, respectively [21]. The dienes obtained during these transformations were successfully converted in Diels–Alder reactions to afford carbocyclic chiral compounds with a sugar backbone. In 2008, Gagné introduced a Ni-mediated Negishi coupling to synthesize alkyl- and aryl-C-glycosides

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• the 2010 Nobel Prize in Chemistry to Heck, Negishi and Suzuki for their contributions to the development of these reactions. Despite their widespread utilization in organic chemistry, cross-coupling reactions have been used rarely for the preparation of furanyl-substituted tpy. The only known

Sexithiophenes as efficient luminescence quenchers of quantum dots

• Christopher R. Mason,
• Yang Li,
• Paul O’Brien,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2011, 7, 1722–1731, doi:10.3762/bjoc.7.202

• %, respectively). In parallel, dibrominated terthiophene 6 was prepared in an analogous fashion to 4a and 4b with 2.2 equiv of NBS. Subsequent Negishi coupling of compound 6 with organozinc intermediates of 4a and 4b, which were prepared by lithiation followed by reaction with zinc chloride, led to the isolation

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki–Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed

• , aminomethylation, sulfuration, oxygenation). However, aryllithiums can rarely be directly involved in transition-metal-catalyzed cross-coupling reactions and are usually transformed into organometallic fragments suitable for efficient Negishi, Stille, Suzuki–Miyaura, and Hiyama cross-coupling reactions [1][2

• the ring-close oxazole, a trend that is evidenced by 1H NMR spectroscopy and attributed to the strong covalent carbon–zinc bond along with the zinc’s low oxophilicity, and this thus allows subsequent palladium-catalyzed Negishi cross-coupling [31][32][33]. This first, highly efficient, stoichiometric

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• -coupling (Negishi reaction) affords the 5-arylated furan 15 in 89% yield. Interestingly, a high chemoselectivity is observed with several heterocyclic dihalides [8][9]. Thus, the tribromopyrimidine 16 provides only the 4-zincated pyrimidine 17. After allylation, the expected allylated pyrimidine 18 is

• obtained in 63% yield. Also, the dibromothiazole 19 allows insertion of zinc only into the most labile C–Br bond (in position 2) leading to the zincated thiazole 20. After Negishi cross-coupling [10][11][12], the 2-arylated thiazole 21 is obtained in 85% yield. Polar functional groups, such as a tosyloxy

• is obtained in 75% yield. Coumarine (46) can be directed zincated leading to the zinc reagent 47. After a Negishi cross-coupling with an aromatic iodide, the substituted coumarine 48 is obtained in 83% yield (Scheme 8 and Supporting Information File 1, Procedure 3) [28]. This procedure tolerates most

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• insertion, the gates of the synthetic arena were spectacularly opened to the 2010 Nobel Prize chemistry and the general theme of transition metal-catalyzed reactions. Thus, the named reactions of Kumada–Corriu, Negishi, Suzuki–Miyaura, Stille and, most recently, Hiyama have all given new insights into how

Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

• Peter Wipf and
• Marija D. Manojlovic

Beilstein J. Org. Chem. 2011, 7, 824–830, doi:10.3762/bjoc.7.94

• to room temperature. However, upon aqueous work-up, none of the desired amine was obtained, even when the more Lewis acidic Cp2Zr(H)Cl prepared in situ by the Negishi protocol [37] was used. In contrast, adding 1.4 equiv of ZnCl2 to the hydrozirconation reaction mixture, according to Suzuki’s

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• formaldehyde as by-products [15]. Another possible approach is based on the direct displacement of a benzylic chloride by sodium sulfite and subsequent sulfonamide formation as shown in Scheme 13 [16]. A more recent method utilises a palladium-catalysed Negishi coupling to access a diverse library of benzylic

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

• Bryan Ringstrand,
• Martin Oltmanns,
• Jeffrey A. Batt,
• Aleksandra Jankowiak,
• Richard P. Denicola and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2011, 7, 386–393, doi:10.3762/bjoc.7.49

• and 3b are volatile so care should be exercised during evaporation of solvent to ensure maximum yields. Negishi coupling of tetrahydropyran 3e with propylzinc chloride following a general literature method [45] using PEPPSI-IR as the Pd(0) source gave tetrahydropyran 3d in 69% yield. Tetrahydropyran

• of the Pd catalyst with ZnBr2 permits efficient hydrogenation without loss of the halogen. The chlorophenyl derivative 3e is a convenient precursor to a variety of 4-alkylphenyl and 4-arylphenyl derivatives that can be obtained via Negishi or Suzuki coupling methods (i.e., 3d). Another such

A short and efficient synthesis of valsartan via a Negishi reaction

• Samir Ghosh,
• A. Sanjeev Kumar and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 27, doi:10.3762/bjoc.6.27

• -tetrazole (6) and its Negishi coupling with aryl bromide 5 are the key steps of the synthesis. This method overcomes many of the drawbacks associated with previously reported syntheses. Keywords: antihypertensive therapy; aryl bromide; Negishi coupling; tetrazole; valsartan; Introduction Valsartan (Figure

• synthesis of sartans: whilst the synthesis of losartan [4] as described in the literature makes use of Negishi [5][6] and Ullmann [7] couplings, the published methods for the preparation of valsartan utilize Suzuki–Miyaura couplings [8]. Of these, Negishi reactions have proved to be very efficient. However

• important goal. In this paper, we report a new, concise and efficient synthesis of valsartan via Negishi coupling. Results and Discussion From a retro-synthetic analysis (Scheme 1), compound 8 could be constructed via Negishi coupling from aryl bromide 5 and 5-phenyl-1-trityl-1H-tetrazole (6), which in turn

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

Synthesis of deep- cavity fluorous calix[4]arenes as molecular recognition scaffolds

• Maksim Osipov,
• Qianli Chu,
• Steven J. Geib,
• Dennis P. Curran and
• Stephen G. Weber

Beilstein J. Org. Chem. 2008, 4, No. 36, doi:10.3762/bjoc.4.36

• , particularly palladium catalyzed cross coupling reactions, including Kumada, Negishi, and Suzuki processes which can be used to append aromatic rings onto the molecule [30][31]. Therefore, 3b was treated with N-bromosuccinimide (NBS) in methyl ethyl ketone (MEK) [32] to give the bromide 4 in 87% yield