Ruthenium- and Rhodium-Catalyzed Direct Carbonylation of the Ortho C−H Bond in the Benzene Ring of N-Arylpyrazoles

Abstract

The direct carbonylation of C-H bonds in the benzene ring of N-phenylpyrazoles via catalysis by ruthenium or rhodium complexes is described. The reaction of N-phenylpyrazoles with carbon monoxide and ethylene in the presence of Ru(3)(CO)(12) or Rh(4)(CO)(12) resulted in the site-selective carbonylation of the ortho C-H bonds in the benzene ring to give the corresponding ethyl ketones. A variety of functional groups on the benzene ring can be tolerated. N-Phenylpyrazoles have higher reactivities than would be expected, based on the pK(a) values of the conjugate acid of pyrazole. The choice of solvent for this reaction is significant, and N, N-dimethylacetamide (DMA) gives the best result.

Rhodium-Catalyzed C−C Bond Formation via Heteroatom-Directed C−H Bond Activation

“…In the earliest report utilizing this approach, Chatani and coworkers demonstrated the reaction of N -arylpyrazoles with CO and ethylene using Rh 4 (CO) 12 as the catalyst (Chart 9). 51 The transformation was tolerant of electron-donating substituents on the arylpyrazole ring ( 124a – d ), in addition to heteroarenes ( 125 and 126 ) and 1- and 2-naphthalene ( 127 and 128 ), although in some cases dialkylation was observed as the major product in the absence of a blocking substituent. Substrates incorporating an electron-withdrawing substituent such as CF 3 or carbonyl functionalities gave poor yields and the starting heterocycle was recovered.…”

Ruthenium‐Catalyzed Carbonylation of ortho CH Bonds in Arylacetamides: CH Bond Activation Utilizing a Bidentate‐Chelation System

“…The reaction involves the regioselective activation of C(sp 2 )ÀH bonds at the ortho CÀH position. [8,9] The reaction of amide 1 a with CO was carried out under reaction conditions identical to those used in the reaction of aromatic amides (Ru 3 (CO) 12 in toluene at 160 8C under 10 atm of CO for 24 h) to give the isoquinoline-1,3(2 H,4 H)-dione 2 a in 93 % yield. The absence of ethylene did not give 2 a, and, in the absence of H 2 O, the yield of 2 a was dramatically decreased to 26 %.…”

A Facile Synthesis of 2,4-Disubstituted Thiazoles Using MnO2

“…After filtration, the mixture was evaporated in vacuo . The residue was chromatographed on silica gel (ethyl Acetate-hexane, 10:1) to give 176 mg (95% yield) of 4-methyl-2-phenylthiazole ( 1a ) [21] as a colorless oil; 1 H-NMR: δ 7.94–7.91(m, 2H), 7.43–7.39 (m, 3H), 6.85 (t, J = 0.96 Hz, 1H), 2.50 (d, J = 0.96 Hz, 3H); 13 C-NMR: δ 167.44, 153.71, 133.72, 129.65, 128.75, 126.34, 113.30, 17.14.…”