C-H activation products

Iridium-catalyzed formation of B-C bonds from arene C-H bonds was first reported by Smith and coworkers [73]. They demonstrated that the archetypal C-H activation products, Cp lr(PMe3)(H)(R), could mediate B-C bond formation (R = Ph, cyclohexyl) and were able to effect the catalytic borylation of benzene with HBpin (8) to produce CgHsBpin and H2 at 150°C (8). 

The C-H activation of allylic and benzylic C-H bonds has considerable application in organic synthesis. Studies by Muller [131] and Davies [130] on reactions with cyclohexene revealed that Rh2(S-DOSP)4 in a hydrocarbon solvent is the optimum system for high asymmetric induction (Tab. 14.13). Although this particular example gives a mixture of the C-H activation product 179 and cyclopropane 180, similar reactions with ethyl diazoacetate gave virtually no C-H activation product. Some of the other classic chiral dirhodium catalysts 181 and 182 were also effective in this chemistry, but the en-antioselectivity with these catalysts (45% ee and 55% ee) [131] was considerably lower than with Rh2(S-DOSP)4 (93% ee) [130]. 

In systems where steric interference is not a factor, C-H insertion at a methylene site is strongly preferred over that at methyl sites. A striking example of this effect is the reaction with 4-ethyltoluene (Eq. 24) [137]. The only C-H activation product formed is 202, derived from C-H insertion at the methylene site. A Hammett study on the benzylic C-H activation indicated that the transition-state build-up of positive charge at the benzylic position is stabilized by resonance. 

C-H insertion a to oxygen would generate p-hydroxy or p-alkoxy esters. Thus, the reaction could be considered as a surrogate of the aldol reaction. In Vol. II, Chap. 16 of this series, the preliminary studies on C-H activation of tet-rahydrofuran were summarized [3]. Since then this reaction has been optimized such that the major C-H activation product 22a can be obtained in 97% ee [17]. The optimum reaction conditions (2 equivalents of THF in hexane at -50 °C) demonstrate the regioselectivity that is possible with this chemistry because no reaction with the solvent was observed under these mild conditions. 

Since the early studies with tetrahydrofurans, new substrates have been explored that are capable of highly diastereoselective reactions. trans-Allyl si-lyl ethers are exceptional substrates as illustrated by the conversion of 23 to 24 [Eq. (11)] [24], The reactions are highly diastereoselective (96-98% de) and in many respects outperform the standard aldol reaction. Even better substrates are tetraalkoxysilanes as shown for the reaction of tetraethoxysilane (25) [25]. In this case, both the enantioselectivity and the diastereoselectivity for the formation of C-H activation product 26 are >90% de and ee. 

Scheme 9.11 Preparation of the alkyl(aryl) rhodium(I) complex 32 from 27b and the conversion of the C—H activation product 33 to the C—C bond activation product 32 via 34 as the...

Azaallyl hydrides undergo many reactions as well as enantiomer interconversion. Heating 40a at 70 °C overnight led to the C-H activation product 41, identified by and 13C NMR (Eq. 44) [24]. Similar C-H activations (Eq. 45) have been observed by Andersen [73] and Scott [74]. 

The P—H bonds of primary phosphines RPH2 add to zirconocene to give unstable zirconium phosphido hydrides CpZr(H)(PHR) from which C—H activation products such as fulvalene complexes [CpZr(/A-PHR)]2(rf r -QoHg) can be isolated.44 The addition of Ph2P(0)H to M(PEt3)3 (M = Pd, Pt) gives (21-X) the Pd derivative catalyzes the hydrophosphinylation of alkynes.45... 

The above systems have also been examined in some detail for their thermodynamic selectivity towards C-H bond activation. As mentioned above, irradiation of Cp Ir(PMe3)H2 in pentane gives a mixture of primary and secondary C-H activation products. Upon heating to 110°C, however, the primary activation product is observed to increase at the expense of the secondary activation products (Eq. 4). This observation indicates that the initial product ratio indeed represented a kinetic selectivity, and that the n-pentyl product is thermodynamically preferred by several kj mol-1, since no secondary products were seen at equilbrium [22]. 

Computational studies of the Rh-P,N system have shown that the C-C activation product is the most stable (A < -12kcalmol relative to the C-H activation product) and its formation is fast and irreversible. C-H activation is fast and reversible. When choosing structure 132 as the entry channel, structure 133 is the common intermediate for both C-H and C-C activations and structure 134 is a possible transition state, all having hypercoordinate carbon atoms. 

This remarkable molecule can be viewed as a snapshot of the desulfurization process taking place unfortunately, the reaction of this compound with hydrogen was not reported. When the analogous Os clusters were used with the same substrates, only C-H activation products were observed for T and DBT, while for BT a minor product arising from a C-S bond cleavage reaction could also be detected. 

However, under certain conditions C-H activation can also be facile and favorable with first-row transition metals. To illustrate this point, just two examples are given here. In 1952, Miller, Tebboth and Tremaine reported the formation of a very stable volatile complex, when cyclopentadiene was passed over reduced iron at 300 The product, dicyclopentadienyliron (later called ferrocene) obviously is a C H activation product of cyclopentadiene (Eq. 1). Much later, Timms was able to show that the same reaction could also be brought about at a temperature as low as —196 °C. There are many examples of similar reactions in the literature. They... 

An asymmetric rhodium-carbenoid insertion at the benzylic position strategy was used as a key step in the synthesis of (+)-imperanene and (-)-a-conidendrin. The C-H activation product with the S configuration can be converted to (+)-imperanene via a reduction/deprotection. (-)-a-Conidendrin can be synthesized via lactonization of the C-H activation product with the R configuration. The stereochemistry of these key intermediates is controlled by using opposite enantiomers of the catalyst. ... 

A study on the reactions of 2-ethylbutanenitrile with the first row transition metal ions Ti to Zn" " shows that the early metals Ti and V+ give mainly C-H activation products whereas and... 

Terminal alkynes also add to [Tp Rh(CNR)]. Irradiation of the carbodiimide complex 1 in neat 1-alkyne leads to the activation of the sp C-H bond. In cases where other activatable C-H bonds were presented, competitive C-H activation at these positions was observed. For example, t-butylacetylene and trifluoromethyl acetylene give exclusively alkynyl hydride products, whereas 1-octyne and trimethylsilylacetylene also give products resulting from methyl group activation. In both of the latter cases, the sp C-H activation products are unstable and convert to the terminal alkynyl products at room temperature after a few days (Scheme 1). Similarly, the activation of arylalkynes leads to mixtures of sp and sp C-H activation products. The unsaturated fragment [Tp Rh(CNR)] was prepared either... 

Irradiation of dihydride 4 in neat terminal alkyne led to C-H activation products, but the lengthy photolysis times led to decomposition products with many of the acetylenes. Methyl hydride 5 proved to be a good precursor for the activation of... 

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