Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (1) [35] was used as starting compound. The synthesis includes the metallation of the free base porphyrin 1 with an excess of zinc acetate or nickel acetate resulting in the corresponding porphyrin Zn(II) and Ni(II) complexes 2a [36] and 2b [37], respectively

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• ) might be due to an easier coordination of acetates to palladium which favors the concerted metallation deprotonation (CMD) mechanism [40]. The regioselectivities observed using acetate bases are consistent with a CMD mechanism. Then, a set of aryl bromides was reacted with lilolidine using 2 mol % of

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• tolerance toward a variety of functionalities on arenes as well as alkynes. The isolated cationic cobalt intermediate (C3) and the mechanistic studies strongly indicate that the reaction proceeds through C–H activation via concerted metallation-deprotonation (CMD) to form cobaltacycle C1. Subsequently

• reagent. Then, imine 9 assisted an ortho C–H metallation by oxidative addition and provides Co–H intermediate D1. Coordination of alkene with D1 and insertion of the alkene to Co–H gives intermediate D3 or D3’, which is converted into product 27 or 28 and low-valent cobalt by reductive elimination

• /Matsunaga and co-workers reported a hydroarylation reaction of activated alkenes with phenyl pyridines 3 in the presence of the air-stable [Co(III)Cp*(benzene)](PF6)2 catalyst, giving hydroarylation products 37 in good yields (Scheme 25) [37]. The reaction proceeds through directed ortho C–H metallation to

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• work focused on the activation of hypervalent iodine [13], and a computational study that suggested a concerted iodination/deprotonation (CID) that is analogous to concerted metallation/deprotonation (CMD) for cationic hypervalent iodine [14]. These studies and others on the electrophilic nature and

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• . Gorelsky calculated that the Gibbs free energies of activation for the cleavage of C–H bonds at C5-position of thiophene or pyrrole derivatives, for reaction which proceed via concerted metallation–deprotonation [38][39][40], are higher than that of thiazoles (see bottom of Scheme 2) [42]. We assume that

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• substrates were prepared by following literature procedures; the halide partner by controlled bromination of 5,10,15,20-tetraphenylporphyrin (TPP) with N-bromosuccinimide followed by metallation with Zn(AcO)2 [31][32] and the tosylhydrazones 2a–c by reaction of the adequate ketones with tosylhydrazines [33

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• features of these cavitands is that although structurally quite complex, because of their well-defined structure they can be readily functionalized [22][23]. For example, directed ortho-metallation and quenching with electrophiles could at first blush theoretically lead to a plethora of products because

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• version of the synthesis published in reference [9]. First, the metallation [21] of 4 with t-BuOK and n-BuLi in hexane followed by addition of prenyl bromide (3-methyl-2-butenyl bromide) at −10 °C afforded the sesquiterpene derivative 5 ([α]D +19.5° (c 1.2, CHCl3)) in 84% yield. The VO(acac)2-catalyzed

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

• deprotonative metallation using the base in situ prepared from LiTMP and ZnCl2·TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the reactions were carried out in hexane containing TMEDA which regioselectively afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and indoles bearing N

• , vincamine, ergotamine, lysergic acid), as well as in pharmaceuticals (e.g., indomethacin, iprindole), agrochemicals (e.g., auxins, pyroquilon), and dyes and pigments (e.g., indigo, indocyanines) [1][2]. The deprotonative metallation [3][4][5][6][7] is a valuable tool for the regioselective functionalization

• ]. Herein, we report our efforts to functionalize N-arylated pyrroles and indoles through deproto-metallation using this mixed lithium–zinc base (Figure 1). We showed earlier, for related substrates, the impact of the different hydrogen acidities on the regioselectivity of the reaction [37][38][40][42][43

Pd(OAc)₂-catalyzed dehydrogenative C–H activation: An expedient synthesis of uracil-annulated β-carbolinones

• Biplab Mondal,
• Somjit Hazra,
• Tarun K. Panda and
• Brindaban Roy

Beilstein J. Org. Chem. 2015, 11, 1360–1366, doi:10.3762/bjoc.11.146

• base. The amide precursor was then subjected to a series of reactions in pursuit of the best reaction conditions for the dehydrogenative cross-coupling process. Assuming that the reaction goes through an electrophilic metallation pathway, it was projected that Pd(OAc)2 would be an excellent starting

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• the ortho-position of 2-(phenyl)phenylphosphonic acid monoethyl ester is not involved in the rate-limiting step and the C–H bond metallation is reversible. To elucidate the mechanism of the present reaction, the reaction was conducted with a stoichiometric amount of Pd(OAc)2 and without the oxidant

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• phospho-Fries rearrangement (a rearrangement initially reported by Melvin et al. [92]). This rearrangement proceeds by an ortho-metallation that can be characterized at a low temperature [93]. Then, the o-lithium species rearranges to produce 2-hydroxyarylphosphonate [94]. The recent publication of Yang

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• reactivity, silver(I) salts and complexes have been used to activate either the nucleophile or the imine. Isocyanides have been found to be versatile reagents in heterocyclic synthesis [82][83]. In particular, the α-metallation of isocyanides was accomplished by Schöllkopf [84] and Van Leusen [85] for the

On the control of secondary carbanion structure utilising ligand effects during directed metallation

• Andrew E. H. Wheatley,
• Jonathan Clayden,
• Ian H. Hillier,
• Alison Campbell Smith,
• Mark A. Vincent,
• Laurence J. Taylor and
• Joanna Haywood

Beilstein J. Org. Chem. 2012, 8, 50–60, doi:10.3762/bjoc.8.5

• observation of two structure-types for the carbanion in solution is explained theoretically and by NMR spectroscopy in terms of cis and trans isomerism imparted by partial double bond character in the arene–(α-C) bond. Keywords: directed metallation; Lewis base; ligand effects; lithium; secondary carbanion

• approaches the reactive position (“ortho lithiation” when deprotonation occurs adjacent to the directing group [2][3], “directed remote metallation” when reaction is non-adjacent [12][13][14][15]). However, the presence of substituents at the ortho position of the aromatic ring introduces the possibility of

• emerged in the last decade or so. These data focused on reactions directed by tertiary amides; with the ortho metallation of N,N-diisopropylbenzamide 1-H and its naphthamide analogue 2-H [21] giving species that have been characterised as solid-state dimers. These metallo-intermediates are each based on a

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• Schöllkopf’s bislactim ether 1 [12] to substituted arynes 2, which, following hydrolysis of the syn-adducts 3, provided α-aryl amino acids 4 with moderate to high enantioselectivities (Scheme 2) [13]. The arynes were produced by a directed ortho-metallation [14] and an elimination sequence, and after attack of

• . DMG = directed metallation group. BHT = 2,6-di-tert-butyl-4-methylphenol. Proposed mechanism of α-arylation. Proposed extension of the methodology to synthesize quaternary adducts. Formation of α-methyl, α-aryl Schöllkopf adduct. Formation of quaternary adducts. Hydrolysis of quaternary adducts

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• hypothesis fails to account for the fact that 57 resisted deprotonation even in the presence of excess base. Moreover, 2,3,4-trimethoxybenzamide, a congener of 57 in which an OMe group replaces the Cl substituent, undergoes ortho-metallation without incident [107], even though the triad of adjacent OMe

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

• Abigail Page and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1327–1333, doi:10.3762/bjoc.7.156

• ; diastereoselective; enantioselective; lateral lithiation; metallation; Introduction One of the first uses of the chiral diamine (−)-sparteine (1) in its now familiar role of controlling asymmetric deprotonation/electrophilic quench reactions [1] was an enantioselective benzylic deprotonation of bis(2,6

• sterically hindered diaryl ether linkage. Results An aryloxy group is a weak director of metallation [20][23], but in preliminary studies we were able to deprotonate and methylate the hindered diaryl ether 6 [10] by treatment with n-BuLi in ether at 0 °C with or without (−)-sparteine (Scheme 2). Methylation

• obtained, suggested that they are insufficiently hindered to exist as stable atropisomers and they interconvert on a relatively short timescale, of seconds to minutes, at room temperature. In order to enhance the ease of metallation of the substrates (6 gives low yield at −78 °C unless sparteine is present

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

• , 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

• ), the introduction in the last years of new organometallic “ate” complexes [8][9], which combine an alkali metal with either magnesium, zinc, aluminium, or copper, has allowed more selective metallation reactions. The milder reaction conditions required make these deprotonation reactions tolerant to the

• Sonogashira coupling and a tandem hydroxylation/heterocyclization reaction. The required o-dihaloanisole derivatives could be prepared by a selective ortho-metallation reaction and subsequent electrophilic quenching with iodine (Scheme 1). Results and Discussion As established in our proposed retrosynthetic

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

• 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

• at the DFT level using the B3LYP method and the 6-311G** basis set were used to probe the energetics of both monometallic and bimetallic systems. In accord with the experimental results, it was found that ortho-metallation was favoured by sodiation; whereas meta- (closely followed by para

• -) 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

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• and R), but in trans-metallation (Scheme 38). Such reactivity has been explained by the reverse polarization of the C–I bond in the fluorinated substrates. Because of the greater electronegativity of CF3 over iodine (3.3 for CF3 and 2.5 for the atom of iodine [127][128]), the iodine acquires a partial

Synthesis of (3R,5R)-harzialactone A and its (3R,5S)-isomer

• Gowravaram Sabitha,
• Rangavajjula Srinivas,
• Sukant K. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2010, 6, No. 8, doi:10.3762/bjoc.6.8

• 2-phenylacetaldehyde 7 with 1,3-propanedithiol in the presence of BF3·Et2O in CH2Cl2 afforded thioacetal 5 in 90% yield (Scheme 2). The epoxide 6 was coupled with the acyl anion equivalent 5 (1.0 equiv), prepared by metallation at –78 °C with 1.0 equiv of n-butyllithium in the presence of BF3·Et2O

From discovery to production: Scale- out of continuous flow meso reactors

• Peter Styring and
• Ana I. R. Parracho

Beilstein J. Org. Chem. 2009, 5, No. 29, doi:10.3762/bjoc.5.29

• we have been able to construct a viable alternative route that explains the observed by-products. Product scrambling occurs through trans-metallation between the intermediate nickel complex 3 formed by oxidative addition of the aryl bromide (Ar-Br), and the Grignard reagent. This results in the

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• ]paracyclophane compounds; aryl sulfonylation and the related sulfenylation facilitates the synthesis of sulfonic acids, sulfonamides and protected thiols [24][25][26] whilst directed metallation has allowed the formation of various sulfides [27][28][29][30]. Very few methodologies allow the synthesis of simple

Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

• John W. Hull Jr.,
• Duane R. Romer,
• David E. Podhorez,
• Mezzie L. Ash and
• Christine H. Brady

Beilstein J. Org. Chem. 2007, 3, No. 23, doi:10.1186/1860-5397-3-23

• /debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of

• position. Although 9 and 10 are co-products (Scheme 1), dibromide 8 is a low-melting solid that can be vacuum distilled to improve purity. Introduction of carboxyl functionality in 8 to give 19 was achieved either by metallation with MeMgBr [11] followed by treatment with CO2 gas, or by a palladium

• the preparation of 23 could also be carried out from 22 via metallation with n-butyllithium in an ether solvent with sub-zero cooling, followed by quenching of the 2-thienyllithium species with CO2. We have found that the choice of solvent for the metal-halogen exchange reaction is important. Diethyl