Microwave‐Promoted Rhodium‐Catalyzed Arylation of Heterocycles through CH Bond Activation

Abstract

Performance‐enhancing ligands: Two new bridged bicyclic phosphines 1 a,b based on the “phoban” skeleton (see structures of their naphth‐2‐ylmethyl bromide salts; P yellow, Br brown, C white) are central to a practical catalytic method for the direct arylation of a variety of nitrogen heterocycles using aryl bromides. Broad functional‐group tolerance was observed, and the use of microwave radiation allowed for short reaction times.

Direct transition metal-catalyzed functionalization of heteroaromatic compounds

“…77 Shortly thereafter, Bergman and Ellman reported a method for Rh-catalyzed microwaveassisted coupling of various azoles 134 with aryl bromides (Scheme 48). 78 Employment of the slightly modified procedure ([RhCl(coe) 2 ] 2 with trialkylphosphine ligand A, bulkier than PCy 3 ) in combination with microwave irradiation allowed for a dramatic shortening of reaction times (40 minutes vs 6 hours reported earlier, 74 Scheme 46).…”

Direct Arylation of Thiazoles on Water

“…[1,2] The approach contrasts with traditional sp 2 -sp 2 cross-coupling chemistry involving stoichiometric organometallic compounds, such as ArB(OH) 2 , ArSnR 3 , ArZnCl, as nucleophilic components. In direct arylation, formally unactivated C À H bonds are used as the functionalization site on the nucleophilic coupling partner.…”

“…[3,4] Nearly all intermolecular (and many intramolecular) heteroarene direct arylations require harsh reaction conditions in terms of high temperatures and corresponding highboiling solvents, such as dimethylformamide (DMF). Indeed, the reaction conditions developed by the groups of Ohta and Miura in their pioneering work on heteroarene direct arylations (anhydrous DMF, 140 8C, inorganic base, Pd(OAc) 2 plus phosphine ligand) [3a, 5] have become the standard operating procedure, being heavily represented amongst existing reports. [1,6] Whilst these vigorous conditions may not cause undue difficulty in the functionalization of simple heteroarenes for medicinal chemistry screening programmes, they represent a serious limitation when applied to the synthesis of more-complex heteroarenes of the type found in natural products.…”

Synthesis of symmetrical di(pyrimidin-2-yl)-1,2,4-triazoles and di(pyrimidin-2-yl)-1,2,4,5-tetrazines

“…This compound is character ized by a very broad NH signal shifted to 14-15 ppm in the 1 H NMR spectrum (in DMSO d 6 ), which is consis tent with the data for 1,2,4 triazole 24 and its 3,5 diphenyl derivative. 25 It should be noted that the NH signal of di(pyrimidin 2 yl)triazole 15, which is present in a mix ture with bis(aminomethylidene)hydrazine 14, is substan tially broadened (up to 11-14 ppm) and is not observed at all in the case of the deuterium exchange in the presence of CD 3 OD. The substantial broadening of the NH signal of compound 15 is apparently attributed to the fact that it exists mainly as the 1H tautomer (this fact was proved for the majority of 1,2,4 triazoles in the studies 24,26,27 ) and to the intramolecular migration of the proton between the adjacent nitrogen atoms of the strongly solvated triazole and pyrimidine rings in degenerate structures 15 and 15( Scheme 3).…”