Substitution iron-catalyzed

Whereas the Prins-type cyclizations reported in this and the preceeding chapter were performed using stoichiometric amounts of Fe salts as Lewis acids, a breakthrough in the field of catalysis was reported in 2009 when the first iron-catalyzed Prins- and aza-Prins cyclization was reported. The catalytic system, which is obtained by combining catalytic amounts of an iron salt with trimethylsilyl halides as a halide source, is widely applicable and promotes the construction of substituted six-membered oxa- and aza-cycles (Scheme 33) [44]. 

In the course of a study on creation of a library of a great number of hetaryl ketones and related derivatives, Szewczyk et al. <2001AGE216> elaborated a ruthenium-catalyzed transformation of heterocycles with activated C-H bond by reaction with olefins and carbon monoxide. Thus, 253 gave 254, albeit in very poor yield. Synthetically, the more straightforward iron-catalyzed transformation was described by Fiirstner et al. <2002JA13856>. These authors reacted 255 with a Grignard reagent in the presence of Fe(acac)3 to afford the 7-alkyl-substituted derivative 256 in reasonable yield (acac = acetylacetonate). 

An example of an iron-catalyzed C-C bond formation reaction was reported in 2001 [89]. Treatment of propargyl sulfides 87 with trimethylsilyldiazomethane in the presence of 5 mol% FeCl2(dppb) gave substituted homoallenylsilanes 88 in good to moderate yields (Scheme 3.43). The silanes 88d and 88e, which bear two centers of chirality, were obtained as 1 1 mixtures of diastereomers. Slight diastereoselectivity (2 1) was seen for the formation 88f, which is an axially chiral allene with a sterogenic center. 

The application of transition metal catalysis provided new opportunities to introduce diverse functionality to the diazepine ring system. Iron-catalyzed cross-coupling of Grignard reagents with the imidoyl chloride 40 provided a convenient and efficient method for substituting the heterocyclic ring (Scheme 9) <20060L1771>. 

The oxidative imination of sulfides and sulfoxides via nitrene transfer processes leads to N-substituted sulfilimines and sulfoximines. This reaction is interesting as chiral sulfoximines are efficient chiral auxiliaries in asymmetric synthesis, a promising class of chiral ligands for asymmetric catalysis and key intermediates in the synthesis of pseudopeptides [169]. However, very few examples of such iron-catalyzed transformations have been described. 

Again FeCl3-6H20 is the catalyst of choice for the benzylation of o-xylene by 4-chlorostyrene (Table 6.2). This iron-catalyzed arylation reaction of styrenes allows the synthesis of a wide variety of 1,1-diarylalkanes employing various styrenes and diverse arenes. Scheme 6.15 illustrates selected examples of successfully synthesized 1,1-diarylalkanes and Table 6.3 shows the diversity of different substituted styrenes employed as benzylating agents. 

In order to investigate the scope and limitation of this iron-catalyzed substitution reaction, various nucleophiles [85] and electrophiles were employed in subsequent years [86]. FeBr2 [87] was found to promote this reaction, also, but stoichiometric amounts were necessary. 

Recently, Taillefer et al. reported an Fe/Cu cooperative catalysis in the assembly of N-aryl heterocycles by C—N bond formation [90]. Similarly, Wakharkar and coworkers described the N-arylation of various amines with aryl halides in the presence of Cu—Fe hydrotalcite [91]. Interestingly, Correa and Bolm developed a novel and promising ligand-assisted iron-catalyzed N-arylation of nitrogen nucleophiles without any Cu co-catalysts (Scheme 6.19) [92]. Differently substituted aryl iodides and bromides react with various amides and N-heterocycles. The new catalyst system consists of a mixture of inexpensive FeCl3 and N,N -dimethylethylenediamine (dmeda). Clearly, this research established a useful starting point for numerous future applications of iron-catalyzed arylation reactions. 

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