Olefins heteroaromatic substrates

The classical method for making tert-butyl esters involves mineral acid-catalysed addition of the carboxylic acid to isobutene but it is a rather harsh procedure for use in any but the most insensitive of substrates [Scheme 6.33].80-82 Moreover, the method is hazardous because a sealed apparatus is needed to prevent evaporation of the volatile isobutene. A simpler procedure [Scheme 6.34] involves use of tert-butyl alcohol in the presence of a heterogeneous acid catalyst — concentrated sulfuric acid dispersed on powdered anhydrous magnesium sulfate. 3 No interna] pressure is developed during the reaction and the method is successful for various aromatic, aliphatic, olefinic, heteroaromatic, and protected amino acids. Also primary and secondary alcohols can be converted into the corresponding /erf-butyl ethers using essentially the same procedure (with the exception of alcohols particularly prone to carbonium ion formation (e.g. p-... 

In 2011, Miura et al. were the pioneers on attaching a directing group in heteroaromatic substrates in order to olefinate them using a Ru(n) catalyst. Heteroarenes such as thiophenes, benzofuran, pyrrole, and indolyl carboxylic acids underwent regioselective o/tAo-alkenylation using [RuCl2(p-cymene)] and Cu(OAc)2 H2O. The presence of the carboxylic acid at C-2 provided the C-3 functionalised product. In contrast, when the carboxylic acid was at C-3, olefination at C-2 was achieved. 

Electrooxidative generation of trifluoromethyl radicals (CF3-) and their synthetic application have been developed since the early 1970s because trifluor-oaeetic acid (TFA) is readily available and one of the most economical starting materials for trifluoromethylation [61]. Heteroaromatics as well as olefins have been employed as substrates for the trifluoromethylation (Scheme 7.1) [62]. 

Protonated heteroaromatic bases are therefore more reactive than simple olefins toward acyl radicals. The radical addition of pivalaldehyde to olefins is, in fact, characterized by a radical chain, whose propagation is determined by decarbonylation of the pivaloyl radical and addition of <-butyl radical to the olefin. The synthetic interest is great in the case of substrates with only one reactive position, such as benzothiazole, ... 

In contrast to the large variety of aromatic, olefinic, and aliphatic aldehydes which can be used as donor substrates, wild-type BFD does not tolerate a modification of the methyl group of acetaldehyde in the case of aliphatic acceptor aldehydes. Apart from acetaldehyde, BFD shows activity with aromatic and heteroaromatic aldehydes as the acceptor substrate, forming enantiomerically pure (R)-benzoin and derivatives (Table 2.2.7.3, entries 6-8) [55]. 

In addition to five- and six-membered N-heteroaromatics, other N-heterocyclic compounds have been found to serve as substrates for C-H carbonylation reactions. Benzoimidazole 13 reacted in the same way with CO and olefins in the presence of Ru3(CO)12, but carbonylation occurred at the C-H bond / to the sp2 nitrogen to give 14 (Table 1). The same relationship between reactivity and the pK, values of conjugate acids of heterocycles was also observed in the /8 carbonylation [4],... 

Copper powder, copper bronze, Cu O, CuO, CuSO, CuCl and CuBr were the first catalysts which were used routinely for cyclopropanation of olefins as well as of aromatic and heteroaromatic compounds with diazoketones and diazoacetates. Competing insertion of a ketocarbene unit into a C—H bond of the substrate or solvent remained an excpetion in contrast to the much more frequent intramolecular C—H insertion reactions of appropriately substituted a-diazoketones or diazoacetates Reviews dealing with the cyclopropanation chemistry of diazo-acetic esters (including consideration of the efficiency of the copper catalysts mentioned above) and diazomalonic esters as well as with intramolecular cyclopropanation reactions of diazoketones have appeared. 

BED [EC 4.1.1.7] is derived from mandelate catabolism, where it catalyzes the nonoxidative decarboxylation of benzoyl formate to yield benzaldehyde. Again, the reverse carboUgatiMi reaction is more important [1488-1490]. As may be deduced from its natural substrate, is exhibits a strong preference for large aldehydes as donor substrates encompassing a broad range of aromatic, heteroaromatic, cyclic aliphatic and olefinic aldehydes [1480]. With acetaldehyde as acceptor, it yields the complementary regio-isomeric product to PDC (Scheme 2.200). 

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