Thiophene, directed metalation

Directive effects on lithiation have also been studied. The regiospecific /3-metallation of A-methylpyrrole derivatives and 2-substituted furans has been effected by employing the directive effect of the oxazolino group (82JCs(Pl)1343). 2-Substituted furans and thiophenes are metallated in the 5-position. The formation of 2-lithio-3-bromofuran on treatment of... 

Thiophene is sufficiently acidic to be directly metallated upon treatment with n-BuLi (see Figure 4.1). This direct lithiation can also be realized with polystyrene-bound 3-(alkoxymethyl)thiophene [96]. The resulting organolithium compounds react as expected with several electrophiles, such as amides (to yield ketones), alkyl halides, aldehydes, and Me3SiCl [96]. 

Methylthiophene is metallated at the S-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy-, and 3-bromo-thiophenes are metallated at the 2-position. 2-Substituents which have been used to direct metallation to C(3) of thiophene include oxazoline, imidazoline, secondary carboxamide, carboxylate, sulfonamide, and -aminoalkoxide. For... 

One of the modes of coordination of thiophene to catalyst surfaces most frequently suggested is the S or 771, in which the bond is formed directly between the sulphur and a transition metal atom. In examples of the S-bonding mode which have been well-characterized by X-ray diffraction, a pyramidal geometry has been found [75], which is also present in the absorption of thiophene on metallic surfaces such as copper [76]. 

In conclusion, an extensive literature is available on the reaction networks that are thought to operate in HD,S of various types of thiophenic molecules besides the great advances that have been made in direct studies on molybdenum sulfides and related catalysts, this is another area in which organometallic chemistry has made an impressive contribution to HD,S catalysis, as a number of reaction pathways and mechanisms for the hydrogenation and hydrogenolysis of thiophenes on metal complexes in solution has been well established with the aid of a variety of physical techniques. 

Animations in this area involve anions of both it-excessive and it-deficient heterocycles, which are generated from the halo compounds or by direct metalation. Most of the animating reagents seem to be applicable except that phenylthiomethyl azide (32) fails with the 2-lithium or 2-copper derivatives of furan, thiophene, N-methylpyrrolc, and (V-methylindole.274 Similarly, chloramine and O-methylhydroxylaminc, but not phenyl azide, fail to aminate 2-lithio-1-methylimidazole 66 and the MeN(Li)OMe nitrenoid does not react with 2-lithiothiophene.97 The reactions that appear to be most widely applicable to heterocyclic carbanions are shown in Eqs. 73,100,101 74,316 and 75.358... 

The directed metalation reaction—lithiation with n-butyl-lithium of a position ortho to a substituent on an aromatic ring—is described. Aromatic systems in which the reaction has been studied are benzene, thiophene, naphthalene, and ferrocene. A systematic listing of the bond types that can be formed at the site of metalation is provided. Also of interest is the assessment of the relative directing abilities of directing substituents and comments and observations on the mechanism of the reaction. Utility of the reaction is indicated by the results from asymmetric-directed lithiation and the synthesis of heterocycles. 

Thiophene. Recent work in the authors laboratories has demonstrated that the directed metalation concept works well in substituted thiophenes once a certain limitation is realized—namely, that the 2,5-positions of thiophene are much more reactive toward metalation than are the 3,4-... 

Since thiophene itself is readily metalated in the 2-position, a 3-position substituent s causing metalation to take place at the 2-position suggests that the ready metalation at a position adjacent to sulfur is further aided by the directing 3-substituent. It has also been found in a few instances that when a blocking group is placed in the 5-position of thiophene, a directing substituent in the 2-position will direct metalation to the 3-position (17). An example of this is shown in Reaction 6. 

Metallated furans and thiophenes are not accessible by direct metallation but can be generated at low temperatures by treating the 3-bromo derivatives with BuLi in... 

Both categories usually contain direct metal-metal bonds. The former type of cluster has been used mainly to study (possible) adsorption modes of thiols, thio-ethers, and thiophenes but desulfurization of thiophenes has also been effected by metal carbonyl clusters. In terms of metal oxidation states, coordination numbers and coordination geometries, the latter type of metal cluster shows greater resem-... 

Deprotonation of neutral species has been dealt with in detail in CHEC-1. In the last few years, the major effort in this area has been towards identification of substituents which would specifically direct metalation to the neighboring CH on the thiophene nucleus. An exhaustive review on directed orf/jo-metalation <90CRV879> has also referred to the use of this strategy in thiophene chemistry. 

Several different substituents located at position 2 of thiophene have shown the ability, fully or partially, to direct metalation to position 3 oxazoline, imidazoline, secondary carboxamide, carboxylate, sulfonamide and a-aminoalkoxide. The ultimate objective is to secure a high-yielding, regioselective route for the synthesis of 2,3-disubstituted thiophenes. 

Similarly, heterocyclic amides can be bis-metallated the dianion (437) can be coupled with different electrophiles, the first attacking the more reactive 3-position, although perhaps predictably yields of 2,3,5-unsymmetrically substituted thiophenes are only moderate. The ability of amide groups in general to direct metallation to the usually less reactive 3-position in these types of heterocycles has been summarized. 

Metalation and Halogen-Metal Exchange.—The direct metalation of thiophens with organolithium compounds and the halogen-metal exchange reaction between halogenothiophens and organolithium derivatives have... 

Once it was realized that heteroaromatic sulfonamides could be prepared and converted to sulfonylureas, and that these compounds possessed many of the desirable hebicidal qualities of the benzene sulfonylureas, a large synthetic effort was started to prepare more examples. Using thiophene and pyrazole as representative examples, we have been able to synthesize all of the positional isomers of the mono- and di-substituted sulfonamides. This paper will outline the major synthetic pathways that we have discovered, emphasizing directed metallation processes and nucleophilic substitution reactions, leading to the preparation of these heterocyclic sulfonamides. Many of tiie methods developed for thiophene and pyrazole sulfonamide synthesis have been extended to the synthesis of pyridine and other heteroaromatic sulfonamides. 

Substituted-2-bridged Sulfonamides. This isomer is the easiest to synthesize due to the propensity of 3-substituted thiophenes to undergo electrophilic substitutions or directed metalations in the 2 position. Thus, the "Harmony" reverse isomer can be prepared from acid 32 via a directed metalation to the 2 position. The usual SO2... 

The ease with which thiophene is metalated in the 2 position can be demonstrated by the following scheme where 3-bromothiophene is first converted to 3-methoxythiophene 41 (11), and then the metiioxy group is used to direct metalation giving the sulfonamide 42. 

Organometallic chemistry is particularly important in thiophene chemistry. Thiophenes can be directly metallated at an a-position using a strong base at low temperature, and the resulting nucleophile will react with electrophiles to effect... 

In some cases, the direct metallation was also applied for the synthesis of 3-fluorothiophenes. Thus, 3-fluorothiophene-2-carboxylic acid 30 was prepared in two steps from the corresponding thiophene-2-carboxylic acid 22 by treatment with n-butyllithium followed by reaction with N-fluorodibenzenesulfonimide [22]. This approach was applied to the synthesis of monomer 32 for thieno[3,4-fe]thiophene polymers 33 used in organic solar cells [23]. 

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