Unactivated Arenes

Keywords Electron-deficient arenes, unactivated 1,3-dienes, bismuth triflate, nitromethane, room temperature, intramolecular double hydroarylation of 1,3-dienes, regioselectivity, substituted indanes... 

Multiple efficient catalysts were reported for the intramolecular process, while the intermolecular process has been studied predominantly for alkynes. The reactivity of the unsaturated fragment decreases in the order alkyne > allene diene > vinyl arene unactivated alkene with the intermolecular hydroamination of simple alkenes representing the most difficult transformation. The hydroamination of all types of carbon-carbon unsaturated fragments will be covered in this chapter. 

Inter- and intramolecular (cyclometallation) reactions of this type have been ob-.served, for instance, with titanium [408,505,683-685], hafnium [411], tantalum [426,686,687], tungsten [418,542], and ruthenium complexes [688], Not only carbene complexes but also imido complexes L M=NR of, e.g., zirconium [689,690], vanadium [691], tantalum [692], or tungsten [693] undergo C-H insertion with unactivated alkanes and arenes. Some illustrative examples are sketched in Figure 3.37. No applications in organic synthesis have yet been found for these mechanistically interesting processes. 

Superelectrophilic reactions have been shown to be particularly useful in various synthetic conversions particularly of unactivated er and 7r-bonds, such as in alkanes and electron deficient arenes. Superelectrophiles have also been used in the synthesis of natural products and biologically active compounds. Superelectrophilic chemistiy has also... 

An acid-catalysed reaction32 of methylenecyclopropanes [e.g. (22)] with various unactivated and mildly activated arenes forms cyclized products in good yield [e.g. 

Similarly, unactivated arenes readily react with thallium(III) trifluoroacetate in TFA to give the corresponding arylthallium trifluoroacetates, ArTl(02CCF3)2, which are stable and do not readily decompose to aryl trifluoroacetates and T1(I) 282-286 The rate of aromatic mercuration is increased by a factor of 7 X 10s in TFA relative to acetic acid as solvent.292... 

The early functional models for this oxidation chemistry were rather simple Udenfriend used iron(II), EDTA, ascorbic acid (as the reducing agent) and O2 to hydroxylate arenes, while Hamilton showed that the same system hydroxylates unactivated C—H bonds (e.g. androsten-3-ol-17-one is converted to androsten-3,7-diol-17-one). Mimoun developed the use of an iron(II)/PhNHNHPh/ H1CO2H/O2 system which is also active for alkane hydroxylation. Curiously, other metals [copperfll), manganese(II), vanadium(II), cobalt(II)] are also active. In the hydroxylation of arenes, an arene oxide is believed to be the intermediate in P-450 dependent systems, because a 1,2-shift of a proton in the arene, the NIH shift is often observed. Neither the Udenfriend nor Mimoun models show such a shift, however. 

In addition to the conversion of unactivated alkanes to alcohols, cytochrome P450 hemes transform alkenes to epoxides, arenes to phenols, and sulfides to sulfoxides to sulfones. Furthermore, they are involved in the biosynthesis and biodegradation of endogenous compounds such as steroids, fatty acids, prostaglandins and leukotrienes. Under anaerobic conditions, P450 will reductively dehalogenate haloalkanes to the corresponding alkanes. 

In addition to the arenes, enolates, and other nucleophiles depicted in Scheme 2.142, FITS reagents are also reactive in the perfluoroalkylation of unactivated alkenes, alkadienes [19], and acetylenes [20] (Scheme 2.146). In contrast with olefin perfluoroalkylation by means of perfluoroalkyl bromides or iodides (Section 2.2.1), this reaction does not follow a free radical mechanism but proceeds via cationic intermediates which can be either trapped by addition of nucleophiles or nucleophilic solvents or quenched by -deprotonation with a base (Scheme 2.147). 

As shown in Scheme 17, C—H bonds are also prone to be activated by formal nitrene transfer from a metal center in a catalytic manner. Tp ML complexes have also induced this transformation, with both sp and sp C—H bonds. The first results were obtained employing Tp Cu(NCMe) as the catalyst for the functionalization of the C—H bonds of the alkyl substituents of arene substrates (Scheme 22). In addition to the benzylic sites, that can be considered as activated by the arene ring, the C—H bonds at the P-carbon in substrates such as ethylbenzene or cumene were also functionalized to a certain extent. The use of the silver-based Tp Ag catalyst afforded the functionalization of unactivated alkanes such as hexane or 2,3-dimethylbutane among others. These systems lack selectivity, a mixture of products derived from the insertion of the nitrene group into all available sites being obtained. It is worth noting that nitrene sources such as Phi = NTs, chloramine-T... 

They were able to extend the scope of the direct arylation to simple, completely unactivated arenes, such as benzenes by development of a palladium-pivalic acid co-catalyst system (Scheme 28) [48]. 

Proch S, Kempe R (2007) An efficient bimetallic rhodium catalyst of the direct arylation of unactivated arenes. Angew Chem Int Ed 46 3135-3138... 

Stuart DR, Fagnou K (2007) The catalytic cross-coupling of unactivated arenes. Science 316 1172-1175... 

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