Transition Metal-catalyzed Bond-forming Reactions at the C-H Bond of Heteroaromatic Compounds

Abstract

Recent progress in the C H coupling reactions of heteroaromatic compounds in our group is summarized. Coupling of thiophene derivatives occurs in the presence of a nickel or palladium catalyst with a base as an additive. Lithium t butoxide and several magnesium amides are effective for the coupling reaction of aryl chlorides, bromides, and iodides. Coupling at the C H bond of thiophene with thienyl halides also occurs smoothly forming a thiophene thiophene bond. The reaction is successfully applied to the polymerization of 2 halo 3 substituted thiophenes leading to highly regioregular head to tail type poly(3 substituted thiophene)s. The reaction of thiazole at the C H bond (2 position) with several secondary amines induces C H, N H coupling with a copper catalyst. J. Synth. Org. Chem., Jpn. 1202In considering the reaction mechanism of thiazoles and thiophenes as shown in Scheme 3, the key for the catalytic reaction would be the palladation reaction at the C H bond. The organopalladium intermediate Aryl Pd Th (Th thiophene) can undergo reductive elimination leading to the arylation product accompanied by the formation of palladium(0). There would be two possible pathways for the formation of Aryl Pd Th: Nucleophilic substitution of a heteroaromatic carbanion, which is formed by proton abstraction, to palladium(II) (path a), or electrophilic attack to palladium and following re aromatization (path b). The former is expected to occur at the acidic C H bond such as the 2 position of thiazole, whereas an electron enriched carbon such as the 5 position of thiazole or the 2 position of thiophene would favor the latter.However, proton abstraction at the less acidic C H bond at the 2 position of thiophene may also be possible if a stronger base is employed and that such new reaction systems may open fresh vistas for the C H functionalization of heteroaromatic compounds. Indeed, this has been recently demonstrated for several coupling reactions with heteroaromatic compounds at various types of C H bonds in the presence of a copper catalyst, in which group I alkoxides, magnesium and zinc amides have been successfully utilized.11 Herewith, our recent efforts on the C H functionalization of thiophene derivatives using relatively stronger bases and transition metal catalysis for the purpose of synthesizing advanced materials with extended π conjugation, and particularly those directed to the preparation of oligothiophenes and polythiophenes are described.On the other hand, it is also important to develop catalytic reactions forming carbon heteroatom bonds as well as the extensively studied carbon carbon bond forming cross coupling reactions. Buchwald Hartwig amination with a nickel or palladium catalyst for the coupling of aromatic halide and amines has been a highly effective protocol to form a carbon nitrogen bond.12 Accordingly, the reaction of amines at a C H bond of heteroaromatic compounds is intriguing as an alternative choice. Our recent efforts concerning a novel C H, N H coupling of azoles using a copper ...

Thermally Induced Self-Doping of π-Conjugated Polymers Bearing a Pendant Neopentyl Sulfonate Group

“…Scheme 1 Preparation of thiophene monomer 4a bearing benzenesulfonate group at the 3position Polymerization of the thus obtained chlorothiophenes 4a was carried out by the reaction with a bulky magnesium amide TMPMgCl•LiCl (2,2,6,6-teteramethylpiperidine-1-yl chloromagnesium: Knochel−Hauser base) 44 to undergo deprotonative metallation. [26][27][28][29][30][31][32][33][34][35] The addition of nickel catalyst 6 5 to the thus formed thiophene−magnesium species followed. Smooth polymerization took place at room temperature as shown in Scheme 2 to afford the corresponding polythiophene 6a in 66% yield as deep orange solid as shown in Scheme 2.…”

“…As shown in Scheme 4, the prepared monomer 4a was employed for statistical copolymerization with 2-chloro-3-hexylthiophene ( 11) with a nickel(II) catalyst. [26][27][28][29][30][31][32][33] Copolymerization of 4a and 11 was carried out using 1-20 mol % of 4a. A mixture of 4a and 11…”

“…Accordingly, the introduction of HT-regioregularity into selfdoping polythiophenes is thereby a significant challenge in materials science. [13][14][15] (Fig 1 ) We considered synthesis of a water-soluble HT-regioregular poly-3-substituted thiophene, which posseses benzenesulfonic acid at the side chain employing deprotonative polymerization of 2-halo-3-substituted thiophene as a monomer precursor is employed [26][27][28][29][30][31][32][33] since we have, indeed, shown that synthesis of several side-chain functionalized polythiophenes have been prepared to date. 34,35 The acidic moiety should be protected during the polymerization employing an organometallic monomer and/or a transition metal catalyst.…”

Cross-Coupling Polymerization of Organosodium for Polythiophene Synthesis

“…Zinc and some other group II metallic species were subsequently used for the preparation of polythiophene to date. − Generation of such an organometallic species has been carried out by a regioselective halogen–metal exchange with a 2,5-dihalo 3-substituted thiophene , when a certain alkyl metallic species is subjected to the dihalogenated precursor. Deprotonation of a 2-halo 3-substituted thiophene at the 5-position with a metal amide has also been alternatively employed to generate metalated halothiophene species 1 . − We have reported that the thiophene species of organolithium is available for polythiophene synthesis (Murahashi coupling polymerization), where we noted the control of a highly reactive organolithium such as 1 (M = Li) for a cross-coupling polymerization catalyzed by a nickel complex. , Polymerization proceeded in a highly regioregular manner with a controlled molecular weight and a relatively narrow molecular weight distribution. We envisaged that it is challenging to utilize much more reactive and less controllable but abundant sodium instead of other metallic species such as lithium, magnesium, zinc, etc.…”

Synthesis of Oligo(thienylene-vinylene) by Regiocontrolled Deprotonative Cross-Coupling

“…It is therefore important to develop concise and practical synthesis of oligo- and polythiophenes in materials science as well as synthetic organic chemistry. We have been engaged in practical synthesis of oligothiophenes and polythiophenes with a head-to-tail (HT) type regioregular structure, which generally exhibits higher performance as a material because of its minimum steric repulsion leading to planar π-conjugated conformation, using a transition-metal-catalyzed cross-coupling reaction at the C–H bond forming a thiophene–thiophene bond …”