Thiophenes pivalic acid

Carboxylic acid additives have been shown to assist in the deprotonation process vide infra). Fagnou and coworkers have used palladium (II) acetate, a phosphine ligand, potassium carbonate and pivalic acid (PivOH) in DM Ac or toluene to prepare several small molecules through the coupling of thiophenes and 2,2 -bithiophenes with arylbromides. An example of a biscoupling of 2,2 -bithiophene with two equivalents of l-bromo-3,5-dimethylbenzene to give 7 is shown in Scheme 19.3. 

All C-H activation procedures for polymers reported thus far have been carried out under dry inert atmosphere using sealed vessels (Schlenk glassware). Similar to small-molecule procedures, polar (DMF, DMAc) and nonpolar (toluene, THE) aprotic solvents have been used and are degassed prior to use. Most thiophene-based monomers are not commercially available and must be synthesized according to literature procedures. It is very important that these monomers be extremely pure and free of all aryl impurities since other aryl bonds may undergo C-H activation and be incorporated into the polymer. All examples have employed palladium (II) acetate or the Herrmann-Beller catalyst. The latter can be prepared from Pd(OAc)2 and tris-(t)-tolyl)phosphine. All phosphine ligands, anhydrous bases and pivalic acid are commercially available and are stored under inert atmosphere. 

The Leclerc group synthesis used DHAP to prepare copolymers containing bithiophene and terthiophene with TPD and FPD monomers." " The polymers are prepared by charging a microwave vial with the dibrominated thiophene, 5-alkylthieno-[3,4-c]pyrrole-4,6-dione (TPD) or 5-alkylfuro[3,4-c]pyrrole-4,6-dione (FPD), Herrmann-Beller catalyst (4mol%), tri(o-anisole)-phosphine (8mol%), CS2CO3 (2.3 equiv), and pivalic acid (0.3 equiv.) (Scheme 19.11). Toluene (0.2 M) is added and the reaction mixture heated to 120 °C under pressure for 24 36 h. The workup for the reaction is the same as that outlined in Example 2. Polymers 36-39 are prepared in moderate to high yields (38-94%). ... 

The C-2 selective oxidative C-H coupling of unactivated pyridines with heterocycles was achieved in the presence of Pd(OAc)2, phenanthroline as the ligand, a silver oxidant, and pivalic acid (eq 145). Moderate to good yields were obtained when heteroarenes, such as thiophenes, indoles, furans, indazoles, or xanthines, were coupled to p3uidine (or p3razine, quinoline, pyrimidine). Virtually no homo-coupling or other regioselective (C-3 or C-4) products were observed in the reaction. 

Low yields were obtained in the absence of pivalic acid however, employing greater than 30% pivalic acid did not further improve yields or reactivity. Substrates that performed well included C3-substituted benzothiophenes, C2-substituted thiophenes, pyrroles, imidazole, triazole, imidazopyridine, thiazole, and oxazoles, which could be efficiently arylated with aryl bromides. Unfortunately, benzofuran produced low yields (29% with 2-bromotoluene), and furans encountered issues with diarylation, which could be minimized by using more sterically hindered aryl bromides. Arylation of indolizines could be achieved, albeit electron-deficient aryl bromides required longer reaction times (16-24 h). Heterocyclic aryl bromides, such as 3-bromopyridine, could also be employed with thiazole. Problematic aryl halides included cyano, nitro, acetyl, pyridyl functionalities, and N-heterocyclic V-oxides. Other coupling partners, such as aryl tri-flates and aryl chlorides, performed poorly under the reaction conditions. Unsuitable heterocycles included unprotected imidazoles, 2-aminothiazole, isoxazole, benzothiazole, and benzoxa-zole, which failed to produce arylated products. 

Silver(I) carbonate functioned as an oxidant in combination with TBAI to provide optimal yields. Pivalic acid was superior to pyridine as an additive. Thiazole, pyrazole, thiophene, and pyrrole substrates could be cross-coupled however, heteroarenes bearing electron-donating substituents afforded better yields compared with electron-withdrawing groups. The reactions proceeded in high regioselectivity at the C2/C5 position. 

The Ar-H functionalization approach has also been used in the preparation of polymers. For instance, a diketopyrrolopyrrole-based polymer was prepared via a palladium-catalyzed direct C-H (hetero)arylation reaction between a di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-l,4-dione and 4,7-dibromo-2,l,3-benzothiadiazole (eq31). The reaction was conducted using palladium acetate as the catalyst and pivalic acid as an additive. A survey of different phosphines demonstrated that molecular weights of the same order and similar polydispersity indexes (PDI) were obtained using tri-terf-butylphosphonium and tri-ferf-cyclohexyl tetrafluoroborate. ... 

A comparison between pivalate-mediated conditions and silver conditions revealed the preference of nucleophilic thiophenes for silver conditions, whereas acidic thiophenes favored pivalate conditions (eq 17). 

---