Phosphine-thiazoles

Scheme 8.13 Hydrogenations of olefins with phosphine thiazole ligands.

The phosphine-thiazole ligand 149 has been shown to promote asymmetric intermolecular Heck coupling of 2,3-dihydrofuran with aryl triflates <07ASC2595>. Microwave irradiation of a mixture of 2,3-dihydrofuran (6 equiv.), aryl triflates (1 equiv.) and DIPEA (3 equiv.) in THF in the presence of Pd2(dba)3 (3 mol%) and the ligand 149 (6 mol%) at 120 °C provides 2-aryl-2,5-dihydrofurans 150 in high enantioselectivity. Other phosphine-thiazole ligands have also been evaluated, and ligand 149 proves to be the best in terms of enantioselectivity. 

Asymmetric hydrogenation of trisubstituted aryl alkenes and aryl alkene esters using iridium-phosphine thiazole complexes 220 have been reported <06JA2995>. The tetrahydrobenzo[rf]thiazole complex (220b) delivers higher enantioselectivity than the cyclopenta[(7]thiazole and cyclohepta[r/]thiazole counterparts (220a and 220c), and replacement of thiazole moiety with oxazole dramatically reduces the enantioselectivity. The... 

The microwave-assisted asymmetric Heck reaction has also been used with success for intermolecular bond formation (Scheme 2.28). Using 2,3-dihydrofuran and phenyl triflate as model substrates, the most active catalyst screened was a combination of Pd2dba3 and a phosphine-thiazole supporting ligand. Heating a THF/DIPEA... 

Tris(thiazol-2-yl)phosphine (L) and tris(benzothiazole-2-yl)phosphine (L) with [( j" -cod)PtMe2] give the cw-[L2PtMe2] complexes where the ligand is coordinated via its P donor center (73JOM(59)411, 76JA6521, 82JOC1489). 

The annulation reaction of thioamides with 2-alkynoates and 2,3-dienoates under the catalysis of phosphine provides 4,5-dihydro-1,3-thiazoles, particularly those with 2-aryl substituents (Scheme 14).35... 

Scheme 15 shows the synthesis of an oxazole 63a and thiazole 63b derivative, accomplished by Yokooji et al. [59]. They employed arylation using tertiary phosphines and bromobenzene with CS2CO3 in xylene to form these compounds. 

The 2,5-diarylation of thiazole can be performed effectively with a bulky phosphine ligand. In this reaction, no mono-arylated product is observed, even in the early stage of the reaction, suggesting that the second arylation proceeds relatively fast (Eq. 19) [22], The selective 2-arylation is accomplished by using Cul and Bu4NF as cocatalyst and base, respectively (Eq. 20) [23]. By using a catalyst system... 

Phosphines are known to impart bielectrophilic character to electron deficient alkynes such as 58 and promote y-addition of nucleophiles to alkynes. Binucleophiles such as thioamides could potentially give two thiazoline isomers 59 and 60. It is proposed that an initial vinyl phosphonium intermediate is formed which prefers to react with hard nucleophiles such as nitrogen rather than sulfur consequently, only thiazole 59 was observed. 

Oxazole and thiazole-based amino acids were shown to undergo novel cyclooligomerisations in the presence of pentafluorophenyl diphenyl phosphinate (FDPP) producing the natural hexapeptide dendroamide A <02H(58)521>. 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

The intramolecular aza-Wittig reaction of azidothioesters provides a new approach to functionalized thiazolines <07AG(E)2701>. Coupling of protected amino acids 79 with azido thiols 80 provides thioesters 81, which are treated with triphenyl phosphine to afford thiazolines 17 in good yields. Similarly, the bis(thioester) 82 is converted into the bis(thiazoline) 19. These thiazolines are readily oxidized to the corresponding thiazoles (vide supra). 

The reaction of sulfur-containing heterocyclic compounds such as thiophenes and thiazoles (Eq. 68) is specifically enhanced by addition of Cul, while the role is not yet definitive [135]. The use of a bulky phosphine ligand such as P(f-Bu)3 also promotes the arylation [141]. 2-Iodothiophenes are polymerized to produce polythiophenes (Eq. 69) [142]. 

Imidazol-2-ylidines and imidazolin-2-ylidenes are the most commonly employed phosphine surrogates in Ru-based metathesis catalysts but a variety of other related carbenes have also been explored. Catalysts 25-29 containing A -aryl-thiazol-2-ylidenes with varying steric bulk of the aryl substituent have been prepared (Figure 9) [29]. 

The reduction with sodium borohydride of isothiazole (418) gives rise to the thiazole derivative (419). Similar results are obtained when the same isothiazolium chloride is treated with triphenyl-phosphine in chloroform (Equation (86)) <93JHC929>. 

However, a truly general method for electron-rich heterocycle arylation was not reported until 2007 [38], Electron-rich, bulky butyl-di-l-adamantylphosphine or /er/-buty I dicyclohexyl phosphine in combination with Pd(OAc)2 afforded the best results, and the former was chosen because of cost considerations. Interestingly, electron-rich AMieterocyclic carbene ligands that facilitate oxidative addition of aryl chlorides to low-valent transition metals are inefficient in heterocycle arylation. A number of structurally diverse electron-rich heterocycles are reactive (Scheme 3). Thiophene, benzothiophene, 1,2- and 1,3-oxazole derivatives, benzofuran, thiazoles, benzothiazole, 1-alkylimidazoles, 1-alky 1-1,2,4-triazoles, and caffeine can be arylated. Electron-rich, electron-poor, and heteroaryl chlorides can be used. 

Tervalent phosphorus acid esters, and triphenylphosphine, attack 2-bromothiazole (34) at bromine in alcoholic solvents to give thiazole and the oxidised phosphorus compounds. A similar attack of tris(diethylamino)phosphine on the bromine atom of bromopentafluorobenzene was used to prepare a series of main-group-four pentafluorophenyl derivatives, e.g. (35). A full paper has appeared on the fluoridation of trimethylsilyl phosphites, or phosphoramidites, with sulphury chloride fluoride. The mild conditions allowed the preparation of sensitive nucleoside derivatives, e.g. (36) and (37). 

Leclerc and coworkers copolymerize monomer 44 with brominated monomers to prepare polymers 15 and 16 (Chart 19.4). The reactions are carried out in a sealed microwave vial, which is charged with 3,6-bis(5-bromothiophen-2-yl)-2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2/f,5//)-dione 45, 2-octyl-thieno[3,4-t( -thiazole 44, Herrmann-Beller catalyst (2mol%), pivalic acid (0.3 equiv.), tri(o-anisole)phosphine (4mol%) and cesium carbonate (3 equiv.) (Scheme 19.10). THF [0.1 M] is added, and the reaction mixture heated to 120 °C under pressure for 24 h. The mixture is cooled to room temperature and... 

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