1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• species can explain the faster ring fragmentation pathway. More recently, Knochel and co-workers developed a higher temperature metalation reaction for 1,4-dithiins, using turbo-Hauser-type bases (Scheme 7) [43]. This allows the selective magnesiation or zincation of 1,4-dithiin (3), respectively, at −40

• [81]. Miglustat is a biologically active analog of the natural product deoxynojirimycin, and its enantiomer also shows a promising profile in early biological activity studies. In future applications of 1,4-dithiane or -dithiin building blocks, the recently described zincation protocol by Knochel and

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

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• be employed after deproto-zincation (interception with aldehydes, phenyl disulfide and allyl bromide, or palladium-catalyzed cross-coupling with aryl halides) [35], we chose the iodolysis, which is the most efficient quench. In addition, it offers the possibility of a subsequent functionalization of

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

• intramolecular carbomagnesiation and -zincation [15] and intermolecular carbocupration with stoichiometric copper reagents has been well established [14][18][25], catalytic intermolecular carbomagnesiation and carbozincation are still in their infancy. This article includes the advances in transition-metal

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

• -group are able to direct the zincation. Thus, the diiodoquinoline 22 is regioselectively zincated (25 °C, 12 h) to intermediate 23 leading to the polyfunctional quinoline 24 in 78% yield after copper(I)-mediated acylation (Scheme 4 and Supporting Information File 1, Procedure 1) [8]. This

• cross-coupling product 40 in 79% yield (Scheme 7) [22]. 1.3 Preparation of heteroaryl zinc reagents by direct zincation of heterocyclic compounds using the new zinc base TMP2Zn·2MgCl2·2LiCl (42) The preparation of zinc reagents by a directed deprotonation was of limited use as no soluble zinc base was

• of the important functional groups in organic chemistry. Thus, the zincation of the formyl-substituted indole 49 is complete within 45 min at 25 °C leading to the zinc reagent 50. After allylation, the 2,3-disubstituted indole 51 is obtained in 71% yield (Scheme 9). Similarly, 2-nitrobenzofuran (52

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• benzo[b]furan derivatives has been developed from 3-halo-2-iodoanisoles bearing an additional methoxy group, which have been accessed through an ortho-zincation/iodination reaction. Two palladium-catalyzed processes, namely a Sonogashira coupling followed by a tandem hydroxylation/cyclization sequence

• , give rise to new and interesting dimethoxy-substituted benzo[b]furans. Keywords: benzo[b]furans; o-zincation; palladium; selectivity; Introduction The directed ortho-metallation (DoM) reaction has been widely used as a powerful and efficient method for regioselective functionalization of aromatic

• coexistence of a wider range of functional groups. In this field, the work of Kondo and Uchiyama is remarkable as they described highly chemo- and regioselective deprotonative zincation [10][11][12], alumination [13], and cupration [14] reactions of some functionalized aromatic and heteroaromatic compounds

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

• David R. Armstrong Liam Balloch Eva Hevia Alan R. Kennedy Robert E. Mulvey Charles T. O'Hara Stuart D. Robertson WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, G1 1XL, United Kingdom 10.3762/bjoc.7.144 Abstract Previously we reported that direct zincation

• of N,N-dimethylaniline by the mixed-metal zincate reagent 1 ((TMEDA)Na(TMP)(t-Bu)Zn(t-Bu)) surprisingly led to meta-metallation (zincation) of the aniline, as manifested in the crystalline complex 2 ((TMEDA)Na(TMP)(m-C6H4-NMe2)Zn(t-Bu)), and that iodination of these isolated crystals produced the

• -) metallation was favoured by direct sodium-mediated zincation. Keywords: alkali metal; crystal structure; isomerisation; metallation; zincation; Introduction While the metallation reaction remains an essential tool for constructing substituted aromatic compounds [1][2], the quest for new improved reagents

Directed aromatic functionalization

• Victor Snieckus

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

• and modification is clearly demonstrated by the work of Jonathan Clayden, Jacques Mortier and Keith Smith; the major influence of DoM tactics are comprehensively demonstrated by the review of Marco Ciufolini; the new wave of very useful magnesiation and zincation is developed by Paul Knochel and