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The purpose of the study is to design synthetic methodologies, especially directed deprotometalation using polar organometallic reagents, to access polysubstituted ferrocenesulfoxides. From enantiopure 2-substituted (SiMe3, PPh2) S-tert-butylferrocenesulfoxides, a third substituent was first introduced at the 5 position (SiMe3, I, D, C(OH)Ph2, Me, PPh2, CH2NMe2, F) and removal of the trimethylsilyl group then afforded 2-substituted ferrocenesulfoxides unreachable otherwise. Attempts to apply the "halogen dance" reaction to the ferrocenesulfoxide series led to unexpected results although rationalized in light of calculated pKa values. Further functionalizations were also possible. Thus, new enantiopure, planar chiral di- and trisubstituted ferrocenes have been obtained, in addition to several original 2-substituted, 2,3- and 2,5-disubstituted, 2,3,5-trisubstituted and even 2,3,4,5-tetrasubstituted ferrocenesulfoxides, also enantiopure. [ABSTRACT FROM AUTHOR]

Effect of divalent metals was studied in the cross-coupling polymerization of thiophenes leading to head-to-tail-type poly-3-hexyl-thiophene. Deprotonation of the C–H bond at the 5-position of 2-halo-3-hexylthiophene by LDA followed by metal exchange was carried out in one pot and following addition of nickel catalyst underwent polymerization. One-shot reaction involving deprotonation/transmetalation/ cross coupling polymerization was also examined with manganese(II) chloride and nickel(II) catalyst. [ABSTRACT FROM AUTHOR]

Due to a wide range of applications in electronic materials, polythiophenes attract considerable attention in organic and polymer syntheses as well as in materials science. For the purpose of developing the practical synthetic protocol, this review focuses on the deprotonative pathway in the preparation of thiophene organometallic monomer, which was shown to be effective employing 2‐halo‐3‐substituted thiophene as a monomer precursor. The thus metallated thiophene monomer was shown to undergo polymerization by nickel(II) complex catalysis, with which highly regioregular head‐to‐tail (HT)‐type polythiophenes were obtained with controlled molecular weight and molecular weight distribution. Several polythiophene derivatives with modified thiophene‐ring and side‐chain structures were shown to be designed in order to achieve the designed functionality as materials. [ABSTRACT FROM AUTHOR]

Xanthone, thioxanthone, fluorenone, benzophenone, 2-benzoylpyridine, dibenzofuran, and dibenzothiophene were deprotonated using a base prepared in situ from MCl2·TMEDA (M = Zn or Cd; TMEDA = N,N,N',N'-tetramethylethylenediamine) and lithium 2,2,6,6-tetramethylpiperidide in a 1:3 ratio, as demonstrated by subsequent iodolysis. The different aryl halides were involved as partners in the N-arylation of pyrrolidin-2-one. In the presence of copper(I) iodide and tripotassium phosphate, and using dimethyl sulfoxide as solvent, the reactions could be performed in yields ranging from 40 to 70%. Most of the products were tested for their antimicrobial, antifungal, antioxidant, and cytotoxic (MCF-7) activity. [ABSTRACT FROM AUTHOR]

Deprotonative metalation has been largely used to functionalize aromatic compounds. The efficiency of such reactions, as well as their regioselectivity, depends on the substituents connected to the rings. In contrast with other groups such as fluorine and methoxy, bromine exhibits a long-range acidifying effect. Here we try to depict this particular effect of bromine through different examples in which deprotometalation takes place at a remote position.

1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N -arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium–zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2′-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line. [ABSTRACT FROM AUTHOR]

Abstract: Benzothiophene, benzofuran, benzothiazole and benzoxazole were deprotometalated using the lithium–zinc combination prepared from ZnCl2·TMEDA (TMEDA= N,N,N′,N′-tetramethylethylenediamine, 1equiv) and lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 3equiv). Subsequent interception of the 2-metalated derivatives using iodine as electrophile led to the iodides in 81%, 82%, 67% and 42% yields, respectively. These yields are higher (10% more) than those obtained using ZnCl2·TMEDA (0.5equiv) and LiTMP (1.5equiv), except in the case of benzoxazole (10% less). The crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2equiv) and Cs2CO3 (2equiv), and using acetonitrile as solvent (no other ligand) to provide after 24h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. Using benzotriazole also led to N-arylation products, but in lower 34%, 39%, 36% and 6% yields, respectively. A further study with this azole evidenced the impact of 2,2,6,6-tetramethylpiperidine on the N-arylation yields. Most of the C,N′-linked bis-heterocycles thus synthesized (in particular those containing benzimidazole) induced a high growth inhibition of A2058 melanoma cells after a 72h treatment at 10−5 M. [Copyright &y& Elsevier]

Abstract: The deprotonating ability of mixed lithium–zinc or lithium–magnesium–zinc combinations containing amido and alkyl ligands in tetrahydrofuran were compared using anisole as substrate and iodine to quantitatively trap the formed arylmetal species. The results showed that the deprotonating ability is hampered if a Grignard reagent is employed to introduce the alkyl ligand, and is reduced when 2,2,6,6-tetramethylpiperidino ligands are replaced by less hindered/basic chiral amido or alkyls. Concerning the interception of the generated lithium–zinc aryl species by aldehydes, the presence of amido ligands leads to side reactions/lower yields, and no clear improvement was observed if lithium–magnesium–zinc aryl species are used. Racemic mixtures to very low enantioselectivities were noted when chiral amido ligands were incorporated in the composition of the bases. Still with enantioselective aryl transfer to aldehyde as purpose, the deprotonating ability of mixed lithium–cobalt combinations containing amido and alkyl ligands were compared using anisole as substrate and anisaldehyde to trap the formed arylmetal species. As before, the deprotonating ability is reduced when 2,2,6,6-tetramethylpiperidino ligands are replaced by less hindered/basic alkyls or chiral amido. The trapping step using aldehydes being in this case more efficient, even in the presence of amido ligands, the alcohols were obtained in higher yields. With recourse to a lower interception temperature, and using only bis[(R)-1-phenylethyl]amino as ligands, 32 and 22% yield, and 69 and 65% ee were obtained using, respectively, anisaldehyde and 3,4,5-trimethoxybenzaldehyde to intercept the metalated anisole. [Copyright &y& Elsevier]

Abstract: The deprotonation of 2-methoxypyridine was attempted using putative (TMP)3FeLi prepared from different iron sources. Using iodine to intercept the metalated 2-methoxypyridine, the best result was obtained from FeBr2 (1equiv) using THF at room temperature; nevertheless, in addition to the expected iodide, the corresponding 2,2′-dimer was obtained (86% total yield). The origin of the competitive formation of the 2,2′-dimer was not identified but mechanisms were suggested to explain its formation. It was observed that the nature of the electrophile employed to trap the 3-metalated 2-methoxypyridine has a strong impact on this dimer formation, the latter being favored using iodine (35% yield), but also benzophenone (28%), benzoyl chloride (22%), methyl iodide (27%), allyl bromide (15%), benzyl bromide (41%), and tetramethylthiuram disulphide (36%); for this reason, the yields of the expected derivatives were only 51, 15, 62, 0, <5, 18, and 0%, respectively. In contrast, using aldehydes readily led to the expected pyridine alcohols without dimerization (59% yield using 3,4,5-trimethoxybenzaldehyde and 66% yield using pivalaldehyde). 2,6-Dimethoxypyridine (in 68% yield), anisole (47%), 2,4-dimethoxypyrimidine (50% at C5 and 3% at C6), 2-fluoropyridine (64%), and thiophene (49%) were similarly converted into the corresponding alcohols after subsequent trapping with pivalaldehyde. Using iodine to trap the 2-metalated anisole did not lead to dimer formation, and 2-iodoanisole was isolated in 71% yield. [Copyright &y& Elsevier]

Abstract: The deprotonation of anisole was attempted using different homo- and heteroleptic TMP/Bu mixed lithium–cobalt combinations. Using iodine to intercept the metalated anisole, an optimization of the reaction conditions showed that in THF at room temperature 2equiv of base were required to suppress the formation of the corresponding 2,2′-dimer. The origin of the dimer was not identified, but its formation was favored with allyl bromide as electrophile. The metalated anisole was efficiently trapped using iodine, anisaldehyde, and chlorodiphenylphosphine, and moderately employing benzophenone, and benzoyl chloride. 1,2-, 1,3-, and 1,4-dimethoxybenzene were similarly converted regioselectively to the corresponding iodides. It was observed that 2-methoxy- and 2,6-dimethoxypyridine were more prone to dimerization than the corresponding benzenes when treated similarly. Involving ethyl benzoate in the metalation–iodination sequence showed that the method was not suitable to functionalize substrates bearing reactive functions. [ABSTRACT FROM AUTHOR]

Keywords: catalyst transfer polymerization; deprotonative metalation; nickel(II) catalysts; regioregular poly(thiophene); side-chain modifications EN catalyst transfer polymerization deprotonative metalation nickel(II) catalysts regioregular poly(thiophene) side-chain modifications 1 1 1 06/04/20 20200602 NES 200602 B Themis b , the Goddess of Justice in the Greek mythology, judges with blindfolded eyes the case thiophene for the catalyst-transfer-type polymerization. The balance scale in her left hand shows the imbalance between dibromothiophene and chlorothiophene, suggesting that smaller weight loss from chlorothiophene leads to the regioregular poly(3-substituted thiophene) in a more atom-efficient manner. Catalyst transfer polymerization, deprotonative metalation, nickel(II) catalysts, regioregular poly(thiophene), side-chain modifications. [Extracted from the article]