Arylation microwave heating

In a recent article by Botella and Najera, controlled mono- and double-Heck arylations in water catalyzed by an oxime-derived palladacycle were described [22], When the reaction was carried out under microwave irradiation at 120 °C in the presence of dicyclohexylmethylamine with only 0.01 mol% of palladium catalyst (palladium acetate or palladacycle), monoarylation took place in only 10 min with a very high turnover frequency (TOF) of > 40000 (Scheme 6.3). As regards diarylation, 1 mol% of the palladacycle catalyst and 2 equivalents of iodobenzene had to be utilized to obtain moderate to good yields of diarylated product. Whereas microwave heating at 120 °C provided a 31% yield after 10 min, a 66% isolated yield of product was obtained by heating the reaction mixture under reflux for 13 h at 100 °C. Here, the... 

A palladium-catalyzed protocol for carbon-sulfur bond formation between an aryl triflate and para-methoxybenzylthiol was introduced by Macmillan and Anderson (Scheme 6.66) [138], Using palladium(II) acetate as a palladium source and 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) as a ligand, microwave heating of the two starting materials in N,N-dimethylformamide at 150 °C for 20 min in the presence of triethylamine base led to the formation of the desired sulfide in 85% yield. 

Microwave promoted, palladium-catalyzed, DPPP-controlled arylation of butyl vinyl ether with 4-tert-butylphenyl triflate afforded the branched arylation product and the corresponding methyl ketone, indicating the occurrence of selective internal a-arylation. Addition of water to the reaction mixture and microwave-heating for 2.8 min at 55 W smoothly produced the hydrolyzed product, 4-tert-butylacetophe-none, with an isolated yield of 77% (Eq. 11.2) [17]. 

Traditional Heck arylation of the corresponding ethyl vinyl ether afforded high yields with most of the aryl bromides investigated (Eq. 11.11). Under continuous singlemode microwave treatment the transformations were complete within 10-12 min [25], Heck reactions without solvent in a domestic microwave oven have been examined by Diaz-Ortiz [26]. The reactions were conducted in closed vessels with reported temperatures of 150 °C. A study was performed in which reactions performed with microwave irradiation were compared with oil-bath-heated reactions with identical reaction times and temperatures. The isolated yields tended to substantially favor the microwave-heated reactions (Eq. 11.12). 

A variety of amides has been formed in moderate to high yields with aryl bromides or iodides as aryl precursors and single-mode microwave heating for 15 min at 150 °C (Eq. 11.15) [29]. Under these conditions, aliphatic, unhindered primary, and secondary amines reacted readily, whereas sterically hindered amines or amines of low nucleophilicity, e.g. anilines, afforded low yields and incomplete conversions. Among the homogeneous catalytic systems tested the most suitable for the use with aryl bromides was a 2 1 mixture of BINAP and Herrmann s palladacycle. 

The synthesis of quinazoline derivatives by the addition of N(3)-C(4) fragment units has not previously been a major synthetic route, but 2,4-dialkyl, alkyl/aryl, and diaryl quinazolines 865 are now readily available by a new procedure that involves activation of A -arylamides 864 with trifluoromethanesulfonic anhydride and 2-chloropyridine, and subsequent addition of nitriles <2006JA14254>. Either normal or microwave heating can be used to perform the final ring-closure step. 

A highly efficient one-pot, two-step microwave procedure has been developed for the synthesis of l-aryl-l/7-indazoles. Microwave heating of 2-halobenzaldehydes or 2-haloacetophenones with phenylhydrazines at 160°C for 10 min quantitatively yielded the arylhydrazones, which were further cyclized to give l-aryl-17/-indazoles via Cul/diamine-catalyzed... 

N-arylation under microwave heating (160 °C, 10 min). Good to excellent yields were observed for hydrazones of 2-iodo-, Z-bromo-, and 2-chlorobenzaldehydes. Notably, a yield of 87% was achieved for a hydrazone of unactivated 2-chlorobenzal-dehyde, whereas using the previously reported palladium catalysis the yield was less than 1% for the same substrate. Application of this methodology afforded the pyrazolo[3,4-. ]pyridine 137 in excellent yield (Equation 49) <2005TL7553>. 

OBC2278>. Aqueous Suzuki reactions conducted with microwave heating were also successful for the coupling of diverse aryl- and alkenylboronic acids to unprotected 2- 6- or 8-halopurines <2006S3515>. 

The arylation of halopyrimidines has also been successfully performed under microwave heating. The Suzuki coupling of this class of substrates was reported to have been published only once before using classical heating and long reaction times40 (Scheme 2.13). 

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