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

• other metals (Pd, Mo, and Ir), copper-catalyzed allylic substitution reactions allow the use of nonstabilized nucleophiles including organomagnesium, organoaluminum, organozinc and organoborane reagents. Moreover, copper-catalyzed allylic substitution reactions usually proceed with high SN2

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• organozinc reagents to give amines [1]; iii) aldehydes to give amides [5][6][7]; iv) base to give imines [8]; v) alkyl and aryl C–H bonds in the presence of acid and visible light to form heterocycles [9][10]. Furthermore they have also been used for chlorination of aromatics in the presence of acid [11

Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• Federation 10.3762/bjoc.11.231 Abstract α,α-Difluoro-substituted organozinc reagents generated from conventional organozinc compounds and difluorocarbene couple with 1-bromoalkynes affording gem-difluorinated alkynes. The cross-coupling proceeds in the presence of catalytic amounts of copper iodide in

• dimethylformamide under ligand-free conditions. Keywords: 1-bromoalkynes; cross-coupling; organofluorine compounds; organozinc reagents; Introduction gem-Difluorinated organic compounds have attracted increasing attention nowadays due to their applicability in medicinal chemistry [1][2] and other fields. Indeed

• difluorocarbene addition to multiple bonds [15]. Recently, we proposed a general method for assembling gem-difluorinated structures from organozinc reagents 1, difluorocarbene, and a terminating electrophile [16][17][18][19][20][21] (Scheme 1). (Bromodifluoromethyl)trimethylsilane [16][17][18] or potassium

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

• 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

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• with iPrMgCl–CuI–LiBr at low temperature in 90% yield. This allene was easily transformed into the precursor 9 by halogen exchange with t-BuLi followed by the addition of C6F13I in 92% yield. Subsequently, the reaction of the diiodo precursor 9 with 2 equiv of an organozinc species derived from 4,5-bis

• 1,3-bis(4-iodophenyl)-1,3-diisopropylallene (9) and organozinc species derived from 4,5-bis(methylthio)TTF. Optical resolution of the enantiomer 3 and its precursor 9 was achieved by a recyclable HPLC on a chiral stationary phase. The ECD spectra were measured, and the obtained spectra allowed for the

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• lactam was performed with an organozinc reagent, the reaction proceeded with high conversion, but the product was isolated in low yield and enantioselectivity (Table 1, entry 4). Alternatively, the authors tried to use the triethylaluminium reagent on the 5-membered lactam (Table 1, entry 7), but the

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• ) were employed in enantioselective organozinc catalysis reactions [23][24][25][26], umpolung catalysis [27] and in organoaluminum [17] and chiral n-butyllithium aggregates [28][29][30][31][32][33]. The chlorophosphite BIFOP-Cl (1) is air-stable and very resistant to hydrolysis (Scheme 2) [13][15]. The

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• halides as has been previously reported [42]. The authors describe generation of a bis-organozinc species which, upon addition to an electrophile, generates an intermediate which can undergo β-hydride delivery to a second electrophile. In this case addition to 5a generates an intermediate organozinc

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• displacement of a halogen atom from phosphorus by an organometallic reagent. This method has proven its usefulness for many years. A variety of organometallic compounds have been described. Most frequently used are the Grignard [21][22] and lithium species. But also organozinc [23][24], organolead [25

• , new approaches were developed including zinc, zirconium and copper reagents. Polyfunctional alkenylphosphine 65 was accessible via the reaction of organozinc derivative 64 with chlorophosphine 22a. The organozinc bromide 64 was prepared from the corresponding alkenyl iodide 63. To prevent oxidation

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• was previously established that zinc is able to reduce cobalt(II) in the presence of an aryl halide to promote the formation of a transient arylcobalt(II) species, which undergoes a fast transmetallation with zinc to furnish an organozinc species [39]. It can thus be assumed that a reductive metal

• organocobalt or an organomanganese species as the key organometallic II. In the first scenario, manganese undergoes a slow transmetallation with the organocobalt species I. It has been shown earlier that zinc salts undergo rapid transmetallations with organocobalt(II) species to furnish organozinc compounds

• . However, as mentioned above, the usage of zinc does not allow the reaction to proceed, so that we assume that the active organometallic species II could not be an organozinc compound. Provided manganese salts cannot undergo the transmetallation step at a comparable rate, but react significantly slower, it

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• synthesis of C-glycosides [12][13][14]. Among these, the Ferrier rearrangement [15] of glycals with protic acids [5][16][17] or Lewis acids [18][19][20][21][22] and carbon nucleophiles such as allylsilanes [23], silylacetylenes [24], silyl enol ethers [25], olefins [26], and organozinc reagents [27] has

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

• reactions are efficient and direct routes to prepare complex and stereodefined organomagnesium and organozinc reagents. However, carbon–carbon unsaturated bonds are generally unreactive toward organomagnesium and organozinc reagents. Thus, transition metals were employed to accomplish the carbometalation

• , organomagnesium and organozinc reagents have been widely employed for organic synthesis due to their versatile reactivity and availability. The most popular method for preparing organomagnesium and organozinc reagents still has to be the classical Grignard method [1], starting from magnesium or zinc metal and

• organic halides [2][3][4][5][6][7]. Although the direct insertion route is efficient and versatile, stereocontrolled synthesis of organomagnesium or organozinc reagents, especially of alkenyl or alkyl derivatives, is always difficult since the metal insertion process inevitably passes through radical

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• in the use of organozinc reagents as nontoxic radical precursors or mediators [1][2][3]. As part of this development, the so-called radical-polar reactions in which alkylzinc reagents are used as mediators in a radical transformation that affords a new zincated species, have emerged as valuable tools

• in synthesis. Pivotal to the processes disclosed so far using alkylzinc derivatives is zinc atom radical transfer [4]. In general terms, the reaction involves a radical chain process initiated by the formation of an alkyl radical from the organozinc derivative in the presence of oxygen [5][6][7][8][9

• ][10][11][12][13][14]. The newly formed radical then undergoes one or more radical transformations before being reduced by the alkylzinc reagent through homolytic substitution at zinc, producing a new organozinc derivative along with an alkyl radical that sustains a radical chain. Overall, the in situ

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

• thioether such as 1 as an activated alkyne. After a carbocupration of the alkynyl thioether 1 with the organozinc reagent 2 in the presence of CuCN·2LiCl [14], the alkenylcopper species 3 should be obtained. Stereoselective quenching with an electrophile (E1) should afford the tetrasubstituted alkenyl

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

• dibromocyclopropane precursors) to carbene rearrangements followed by hydrogen shifts. The above C3-dimerization pathway (Scheme 3) via organozinc compounds goes back to Vermeer et al. and appears to be not only the most general route to alkylated conjugated bisallenes [27][28][29][30][31], but also to many other

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

• Kyle F. Biegasiewicz,
• Michelle L. Ingalsbe,
• Jeffrey D. St. Denis,
• James L. Gleason,
• Junming Ho,
• Michelle L. Coote,
• G. Paul Savage and
• Ronny Priefer

Beilstein J. Org. Chem. 2012, 8, 1814–1818, doi:10.3762/bjoc.8.207

• in obtaining high stereoselectivity, and thus we decided to switch to Michael addition with organomagnesium and organozinc reagents. Since the copper source that produced the highest ee value with the cyclopropanation above was Cu(I) triflate tetrakisacetonitrile, we decided to initially focus on

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

• -glycosides employing different metalated arenes with persilylated 1-iodoglucals [20]. These proved to be particularly reactive to organozinc and organoboron compounds, whereas Hayashi successfully disclosed an approach to react simple stannylated or even electron-poor olefins with 2-bromoglucals in Stille

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

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

• . Experimental details are given for the most important reactions in the Supporting Information File 1 of this article. Keywords: cross-coupling; heterocycles; insertion; metalation; organomagnesium; organozinc; Introduction The functionalization of heterocyclic scaffolds is an important task in current

• presented. Review 1 Preparation of heterocyclic zinc reagents Organozinc compounds [1][2][3] are important synthetic intermediates as they are compatible with a broad range of functional groups. The reactivity of a carbon–zinc bond is quite low, and therefore, reactions with organic electrophiles often

• a result of the high thermal stability of organozinc reagents. A Pd-catalyzed cross-coupling of 59 or a copper(I)-mediated acylation of 62 affords the products 60 and 63 in 80–95% yield (Scheme 10 and Supporting Information File 1, Procedure 4) [30]. 2 Preparation of heterocyclic magnesium reagents

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• usually inert towards orthodox organozinc reagents including benzene [15] and naphthalene [16]. These studies – that have been structurally supported by X-ray crystallography in tandem with NMR spectroscopy – have uncovered the chemical synergy that these mixed-metal alternatives can exhibit, which

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates is described. This route involves the formation of an imine, which is used without isolation, followed by its activation by the carbonyl-containing electrophile and the trapping of the acyliminium by an organozinc reagent. Most

• steps are conducted concomitantly to render the procedure as practical and straightforward as possible. Therefore, the whole experimental protocol takes less than two hours. Keywords: acyliminium; amides; carbamates; multicomponent reactions; organozinc reagents; Introduction Diarylmethylamines

• ], or organozinc compounds [24][25]. However, although these are recognized as mild multi-purpose reagents, sole examples of their use in nucleophilic additions on acylimium salts consist, to the best of our knowledge, of the phenylation of quinolinium salts using diphenylzinc [26][27]. Recently, our

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• sulfoxides 36 in quantitative yields (Scheme 19) [37][38][39][40] that can be further used in organic synthesis [41][42][43]. However, to obtain functionalized dialkylated ethylenic sulfoxide species, the addition of functionalized organozinc species is required. Upon treatment with (FG-R2)2Zn (2 equiv) or

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

• , the use of organozinc compounds provides better transmetalation activity than that obtained by the use of organoboron reagents as well as good chemoselectivity since most common functional groups are not attacked by organozinc species. Although preparations of several biphenyl ring systems related to

• -pentanoyl-L-valinate (5) [9] in 70% yield. Ortho-metalation of 5-phenyl-1-trityl-1H-tetrazole (6) [10] with n-butyllithium at 25 °C followed by treatment with zinc chloride at −20 °C gave the desired organozinc chloride compound. Coupling of the latter with aryl bromide 5 in presence of a catalytic amount

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• ]. On the other hand, enantioselective arylation of aldehydes with organozinc reagents appears as a most convenient alternative, since the initial aldehyde undergoing addition presents two very different groups (namely, a H atom and an aryl group) and hence offers good opportunities for enantiocontrol