Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field. Keywords: conjugate additions; electron-deficient alkenes; enantioselective catalysis; extended Michael acceptors; organometallic nucleophiles

• provided dramatic breakthroughs during the last two decades. This review aims to describe the early examples and recent advances in copper-catalyzed asymmetric conjugate additions of organometallic reagents to extended Michael acceptors. First, seminal reports dealing with the reactivity of extended

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

• catalyzed by Pd and Ni, exploit a wide range of organometallic reagents of Mg, Zr, Zn, Sn, Al, B, Si and In as sources of nucleophiles. Among these metals/non-metals, Al offers a unique feature due to its high chemoselectivity and Lewis acidity [10][11][12]. In addition, Al also has low toxicity and is an

• inexpensive and earth-abundant metal. Organoaluminum reagents can be prepared directly from metallic aluminum [13][14][15], which further highlights the potential scope of these reagents in organic synthesis. However, despite extensive investigations and applications of organometallic reagents of Si, B, Mg

• , Zn and Sn in cross-coupling, the utility of organometallic complexes of Al are limited [13][14][16][17][18][19][20][21]. In many cases, direct transmetalation of organoalanes to Pd are sluggish and require ZnCl2 or CdCl2 to facilitate reactions through sequential transmetalations [19]. In some cases

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• ], but also for lanthanides and actinides [11][12], as well as for main group elements [12][13]. Countless applications in homogeneous catalysis have already taken advantage of the remarkable stereoelectronic properties and structural diversity of these organometallic species [14][15][16][17]. To give

• analogues. It turned out, however, to be highly hygroscopic, which hindered its purification and subsequent reactions with moisture-sensitive bases or organometallic compounds. Other counterions were found to alleviate this tendency. In particular, the replacement of HCl with aqueous HBF4 in the original

• to the large community of organic and organometallic chemists working with NHCs. Structures of the imidazolium and imidazolinium salts discussed in this study and their acronyms. Various synthetic paths leading to the formation of NHCs. Retrosynthetic path for the preparation of symmetrical

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

• nitrostryrenes (with the NO2 serving as a leaving group) [20], were employed. Herein, we report that 1-bromoalkynes, which are known to be involved in reactions with various organometallic compounds [22][23][24][25][26][27], can be used as suitable coupling partners for difluorinated organozinc compounds 2. This

Ru complexes of Hoveyda–Grubbs type immobilized on lamellar zeolites: activity in olefin metathesis reactions

• Hynek Balcar,
• Naděžda Žilková,
• Martin Kubů,
• Michal Mazur,
• Zdeněk Bastl and
• Jiří Čejka

Beilstein J. Org. Chem. 2015, 11, 2087–2096, doi:10.3762/bjoc.11.225

• ), with large BET areas and pore volumes, proved to be very suitable supports, due to easy attachment of bulky organometallic complexes onto silica surface ensuring rapid diffusion of reactants to the active catalytic sites [5][6][7][8][9][10][11][12]. Several strategies of immobilization have been

• ] and such zeolites offer the possibility of their modifications with organometallic moieties in a similar way as mesoporous molecular sieves. Limbach et al. [20] used MWW material as a support for Ru heterogeneous catalyst for cyclooctene oligomerization, however, its activity was rather low. In this

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• General procedures All experiments with organometallic compounds were performed under a dry nitrogen atmosphere using standard Schlenk techniques or in an MBraun drybox (O2 < 2 ppm). NMR spectra were recorded with a Varian Inova instrument (300.1 MHz for 1H, 75.9 MHz for 13C, and 121.4 MHz for 31P) and an

• from commercial sources, and they were degassed and stored in the dry-box when directly used in combination with organometallic complexes, and otherwise were used without further purification. H2ITap∙HCl, complex 8, as well as DEDAM and DAMA were synthesized according to literature procedures [61][71

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

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• : benzimidazolium salts; bulky ligands; cyclization; ligand design; N-heterocyclic carbenes (NHC); ring formation; Introduction Imidazole-based N-heterocyclic carbenes (NHCs) are stable systems serving as ancillary ligands mainly to construct organometallic complexes. These NHCs are sterically and electronically

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• ; oxaphospholanes; phosphinates; phosphine oxides; Introduction Organophosphorus compounds containing phosphorus to carbon bond(s) are widely used in organic transformations. Textbook examples are the Wittig and the Horner–Wadsworth–Emmons reactions. Moreover, the vast majority of ligands used in organometallic

• fact that the γ-hydroxypropyl substituent, which results directly from the ring opening of the phospholane, could provide a second ligation site upon complexation of the corresponding phosphines to a transition metal catalyst. These P,O bidentate ligands are quite useful in organometallic compounds

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• -methylamide) is widely used for the conversion of less reactive amide moieties into other carbonyl functionalities [8][9]. The two oxygen atoms of the methoxy and carbonyl groups coordinate to the organometallic reagents, thereby suppressing further reaction with the obtained aldehyde or ketone. However, this

• activation of the carbamoyl group and for preventing over-addition by organometallic reagents. Isoxazole-3-carboxamide 3 was successfully converted in a similar fashion. Thus, as shown in Figure 1, nitrile oxide 2 serves as an equivalent of functionalized nitrile oxides 4, thereby improving the synthetic

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• showcased the generation and use of organometallic species (i.e., Grignard reagents) in flow synthesis as well as in-line React-IR monitoring in order to precisely control the onset of late stage flow streams that are affected by dispersion effects thus marking the first use of this now commonly

• incorporated analysis technique. As the safe use of organometallic reagents has emerged as a key facet of flow chemical synthesis [58], the ITC reported on the design and implementation of a dual injection loop system that could deliver solutions of organometallic reagents (i.e., LiHMDS or n-BuLi) as a pseudo

• -continuous process [59]. This protocol enables loading of a second loop with the unstable organometallic reagent whilst the first loop (previously filled with the same solution) is being directed to the intended flow transformation. Once this first reagent loop is empty, an automated protocol switches the

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• activity is still mandatory in these kind of reactions. Among various ligands, N-heterocyclic carbenes (NHCs) have gained greater importance in organometallic chemistry. Unlike phosphanes, NHCs are not toxic and insensitive to air, heat and moisture. Moreover, the introduction of substituents onto the

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

• Huixin Jiang,
• Virginia Mazzanti,
• Christian R. Parker,
• Søren Lindbæk Broman,
• Jens Heide Wallberg,
• Karol Lušpai,
• Adam Brincko,
• Henrik G. Kjaergaard,
• Anders Kadziola,
• Peter Rapta,
• Ole Hammerich and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2015, 11, 930–948, doi:10.3762/bjoc.11.104

• , but the interaction can here also be increased by “doubly-bridging” them [13]. Those redox groups that have shown the best interaction along the all-carbon bridges are the organometallic metal centres Re(NO)(PPh3)Cp* [24], Ru(dppe)Cp* [25], and Fe(dppe)Cp* [26] (Cp* = 1,2,3,4,5

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• their profound biological importance, there are different routes reported for their synthesis but the common ones are: nucleophilic substitution of an activated glycosyl donor with organometallic aryl derivatives, cross-coupling of aryls with glycals, Friedel–Crafts arylation at the anomeric centre of

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• polyheterocycles [22][23][24]. It is worth of mentioning, that the described hetero-Diels–Alder reactions with aromatic thioketones as heterodienes, display certain similarities to the reported organometallic pathways observed in their reactions with triiron dodecacarbonyl Fe3(CO)12 [25][26]. Experimental General

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

• copper in CA reactions will preferentially form the 1,4-addition product [1]. Since then, copper has been the most commonly used metal in DCA and ECA reactions. In terms of the nucleophiles that are used, mainly alkyl organometallic reagents derived from zinc, aluminium, lithium and magnesium are used [1

• ][3][4]. Alkenyl, alkynyl and aryl organometallic reagents have been used less frequently [78][79][80][81][82][83][84]. Feringa and co-workers reported the first copper-catalyzed ECA reactions of α,β-unsaturated lactams in 2004 [22]. They were able to perform these reactions in high yields and

• . (Note: In contrast, there have not been any rhodium-catalyzed CA reactions of alkyl nucleophiles.) Finally, (3) no 1,2-addition is observed in the rhodium variant because the organometallic reagents that are used are less reactive than the organolithium and -magnesium reagents used in the copper

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• and not sustainable. Similar to the redox properties of these organometallic complexes, some metal-free organic dyes such as Eosin Y, Rose Bengal, Fluorescein, and Methylene Blue, have shown superiority of their applications as photocatalysts, which are easy to handle, environmentally friendly

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• investigated for a wide range of applications in inorganic and organometallic chemistry [20][21][22][23][24][25]. Unfortunately, the synthesis of 2,2’-bipyrazyl (bpz) is quite challenging compared to the syntheses of other, structurally similar bidentate bisazene ligands. Various methods for the preparation of

• of bpz. An improved synthesis of this ligand would be useful both in the context of the growing interest in photoredox catalysis as well as other organometallic and inorganic applications of bpz-supported transition metal complexes. Our optimization studies for the reductive coupling of 2

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

• 10.3762/bjoc.10.316 Abstract Nucleophilic trapping of iminium salts generated via oxidative functionalisation of tertiary amines is well established with stabilised carbon nucleophiles. The few reports of organometallic additions have limited scope of substrate and organometallic nucleophile. We report a

• novel, one-pot methodology that functionalises N-substituted tetrahydroisoquinolines by visible light-assisted photooxidation, followed by trapping of the resultant iminium ions with organometallic nucleophiles. This affords 1,2-disubstituted tetrahydroisoquinolines in moderate to excellent yields

• . Keywords: iminium salt; organometallic; oxidative functionalisation; photoredox catalysis; tetrahydroisoquinoline; Introduction Tetrahydroisoquinolines (THIQs) are structural motifs prominent within biologically active natural products and pharmaceutical compounds [1][2]. From (−)-carnegine (1, a

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• reactive aldehyde [18], post-MBH modifications [19], an organometallic approach [20] and other strategies [21][22]. With comparatively few reports with respect to the significant literature on other activated alkenes in the MBH field, acrylamide thus requires further development and expansion of its scope

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

• ][9][10][11][12][13][14][15][16]. However, an organometallic derivative must be prepared to perform such reactions. In 1990, Ohta and co-workers reported the Pd-catalyzed direct arylation of heteroaromatics using aryl halides as coupling partners via a C–H bond activation [17][18]. Since then Pd

• than other Pd-catalyzed cross-coupling reactions as it avoids the preparation of an organometallic derivative and also as the major byproducts of the reaction are not metallic salts but a base associated to HX. The metal-catalyzed direct arylation of a wide variety of heteroarenes using aryl halides as

Design and synthesis of novel bis-annulated caged polycycles via ring-closing metathesis: pushpakenediol

• Sambasivarao Kotha and
• Mirtunjay Kumar Dipak

Beilstein J. Org. Chem. 2014, 10, 2664–2670, doi:10.3762/bjoc.10.280

• caged systems. At the same time non-participation of 24 in the RRM reaction reveals that systems which contain a sterically hindered cyclohexene ring are not suitable candidates for the tandem metathesis sequence. Experimental General Reactions involving organometallic species were carried out under

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

• Jonathan Potier,
• Stéphane Menuel,
• David Mathiron,
• Véronique Bonnet,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2014, 10, 2642–2648, doi:10.3762/bjoc.10.276

• ; phosphane; polymer; Introduction Although aqueous organometallic catalysis has been developed long before P. T. Anastas and J. C. Warner set out the foundations of Green Chemistry [1], the very essence of this concept relies on several of the twelve fundamental principles. As such, the use of effective

• catalysts and water as a solvent greatly contribute to the development of eco-friendly industrial processes. The most impressive example of industrial application that makes use of aqueous organometallic catalysis is undoubtedly the Ruhrchemie/Rhône-Poulenc process which allows conversion of propene mainly

• supercritical CO2, ionic liquids or fluorous phases have been used to immobilize the organometallic catalyst [3][4][5]. Co-solvents, surfactants, amphiphilic phosphanes, molecular receptors, polymers or dispersed particles have also been investigated to favour contacts between the aqueous and the organic

Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer

• Francesco Trotta,
• Fabrizio Caldera,
• Roberta Cavalli,
• Andrea Mele,
• Carlo Punta,
• Lucio Melone,
• Franca Castiglione,
• Barbara Rossi,
• Monica Ferro,
• Vincenza Crupi,
• Domenico Majolino,
• Valentina Venuti and
• Dominique Scalarone

Beilstein J. Org. Chem. 2014, 10, 2586–2593, doi:10.3762/bjoc.10.271

• organometallic reactions [1] to emulsion polymerization [2][3][4]. By reacting CDs with suitable crosslinking agents, nanostructured hyper-cross-linked materials, known as nanosponges, can be obtained [5][6][7]. Currently there is a growing interest in the synthesis of soluble β-CD-based polymers, which is a

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• carboxylic acids from CO2 under relatively mild conditions, reactive organometallic nucleophiles such as Grignard reagents can be used, generating a large amount of waste [21][22][23][24]. Electroreduction of CO2 can be a worthy alternative for these dangerous energy-intensive processes, replacing toxic or

• electrons is determined by the applied voltage [25]. Since the electroreduction takes place on a cathode surface, the need for complex homogeneous organometallic catalysts is minimized. Furthermore, electricity will be increasingly of renewable origin in the future, making organic electrosynthesis a

• increase the selectivity for the C6 product, dissolved nickel and iron redox mediators have been used [48][53][54]. The need for such organometallic complexes could be eliminated by direct electrocarboxylation on nickel or stainless steel cathode surfaces [49][50]. Substrates with an internal conjugated