Borylation of alkanes

The reactions of alkanes with borane reagents occurs in the presence of late transition metal catalysts to form products from the replacement of a terminal C-H bond by a boryl group, and these are the first reactions to form products with a functional group in the terminal position with such high selectivity. In 1999 and 2000, Hartwig and 

The products from these reactions are common reagents in organic chemistry. The boronate esters can be oxidized to the corresponding alcohols, oxidized with periodate to theboronic acid, converted to the difluoroalkylborates, or used in palladium-catalyzed CTOss-coupling reactions. -  

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Thus, the initial result of the stoichiometric boiylation of arenes was discovered serendipitously. However, the development of this initial observation into the catalytic borylation of alkane C-H bonds was largely based on the design of complexes for the stoichiometric functionalization of alkanes and then the catalytic functionalization of alkanes. 

In contrast to the borylation of alkane C-H bonds, the coupling of aryl halides with amines was based on a literature precedent from another group published about a decade before our initial studies. Kosugi, Kameyama and Migita published the coupling of aryl halides with tin amides." Mechanistic studies we conducted on this process led us to the perhaps obvious realization that the reaction" could be conducted with amines and a silylamide base instead of tin amides (equation 4)." Surveys of bases with similar p a values led Janis Louie to conduct reactions with alkoxide bases. Similar studies were conducted at nearly the same time by Steve Buchwald and coworkers."... 

The regioselective borylation of alkanes can be achieved either catalytically or stoichiometrically using a host of metal complexes such as rhenium analogs. Such processes can be photochemically or thermally induced (Equation (19)).30 30a 30c... 

The rhodium-catalyzed borylation of alkanes is applied to regiospecific functionalization of polyolefines.165,165a The reaction of polypropylenes (atactic, isotactic, and syndiotactic) with B2pin2 in the presence of Cp Rh( 74-C6Me6) catalyst at 200 °G affords the borylated polymers, which are treated with basic hydrogen peroxide in a mixture of THF and H20 to oxidize the boronate esters to the corresponding alcohols (Scheme 20). The hydroxylated polymers contain 0.2-1.5% hydroxymethyl side-chains. 

For each case we will also present catalytic analogues, namely (1) the activation of methane to form methanol with platinum, the reaction of certain aromatics with palladium to give alkene-substituted aromatics, and (2) the alkylation of aromatics with ruthenium catalysts, and the borylation of alkanes and arenes with a variety of metal complexes. 

Scheme 1. Borylation of alkanes by B2pin2 and HBpin reagents.

The mechanism of thermal borylation of alkanes seems to be similar to that of photochemical borylation of alkanes. The most active precatalysts for thermal alkane borylation, Cp Rh( 4-C6Me6) and Cp Rh(j/2-C2H4), are converted to mixtures of Cp Rh(Bpin)3(H) and Cp Rh(Bpin)2(H)2 in the catalytic reactions [48], Reaction of HBpin or B2pin2 with Cp Rh(Bpin)2(H)2 yields Cp Rh(Bpin)3(H). Furthermore, reaction of Cp Rh(Bpin)3(H) with alkanes and arenes as solvent yields Cp Rh(Bpin)2(H)2. Both species are kinetically capable of being catalysts of the borylation of alkanes. 

Computational studies performed on model complexes in collaboration with Hall and coworkers suggest that alkane borylation may occur by a ej-bond metathesis pathway (Scheme 3) [48]. The proposed mechanism for the borylation of alkanes by 1 begins with elimination of HBpin to generate the 16-electron complex Cp Rh(Bpin)2. This complex then forms a <7-complex (3) with the alkane. The vacant p-orbital on boron then enables cr-bond metathesis to generate a o-borane complex (4). Reductive elimination of the alkylboronate ester product and oxidative addition of B2pin2 then regenerate 1. 

Both Cp Re(CO)3 and Cp Re(Bpin)2(CO)2 catalyze the photochemical borylation of alkanes and alkyl ethers (Table 1). The yield of the photochemical borylation of alkanes depends on the steric hindrance around the methyl groups. For example, the borylation of pentane proceeds with higher yields than the borylation of methylcyclohexane (Table 1, entries 1 and 2), and the functionalization of the less hindered 4-position of isopentane occurs more than three times faster than the borylation of the more hindered 1-position (Table 1, entry 3). The greater yield for borylation of n-butyl ether compared with tert-butyl ethyl ether (Table 1, entries 4 and 5) also indicates that the efficiency of borylation depends on the steric accessibility of the methyl groups. The borylation of alkanes with H Bpin as reagent, which occurs under thermal conditions, was not observed under photochemical conditions. 

Scheme 4. Site selectivity in the borylation of alkanes with remote electronegative atoms.

Photochemical and Thermal Borylation of Alkanes 605 John F. Flartwlg and Joshua D Lawrence... 

Direct borylation of hydrocarbons catalyzed by a transition metal complex has been extensively studied by several groups and has become an economical, efficient, elegant, and environmentally benign protocol for the synthesis of a variety of organoboron compounds. The Rh-, Ir-, Re-, and Pd-catalyzed C-/H borylation of alkanes, arenes, and benzylic positions... 

Initial reports on the borylation of alkanes using isolated transition-metal-boryl complexes date back to 1995, when Hartwig showed that Cp Re(CO)2(Bpin)2 converts pentane to 1-borylpentane with high regioselectivity. " The catalytic C-H borylation of alkanes with Cp Re(CO)3 using photochemical activation was demonstrated soon thereafter (equation 25). Also, an efficient thermal process that involves the use of rhodium catalysts has since been developed (equation 26). It is interesting to note that this methodology is not restricted to small molecules, but has recently been exploited for the direct side-chain functionalization of polyolefins. ... 

Reactions of the type shown in equation 11.34 have been run by Hartwig and thoroughly analyzed by theory at the DFT level. A reasonable explanation for the borylation of alkanes and arenes is the cr-CAM mechanism via path c.107... 

Recently, it was also shown [74] that pentamethylcyclopentadienyl rhodium and iridium complexes with labile dative ligands catalyze the borylation of alkanes at the terminal position under thermal conditions (Scheme 9). It was proposed that Ir(V) and Rh(V) boryl complexes act as intermediates in these reactions. Reaction of Cp IrH4 with HBpin gives Cp Ir(Bpin)(H)3 and Cp Ir(Bpin)2(H)2. Both of the two Ir(V) boryl complexes react with octane to give octylboronate ester [75], though it is still unclear regarding the role... 

Important work by Chen et al. [123b] has shown how borylation of alkanes can be achieved both photochemically and thermally from diboron reagents to give alkylboranes (Eq. 2.43). The best catalysts, [CpRh(ethylene)2] and [Cp Rh(r/ -CeMce)], are active at 150°C. The B-B bond oxidatively adds to the metal probably followed by CH oxidative addition. Reductive eMmination gives rise to a new B-C bond being formed. Functionalization occurs at the terminal position of a linear alkane as in the alkane chemistry described above. Since C-B bonds are in principle precursors to a wide variety of functional groups, this reaction has great promise for future development. 

Recently, rhodium-catalyzed direct borylation of alkane with diboron was reported [50], where Cp Rh(ri -CgMeg) (Cp =C5Me5) was used as a catalyst. This reaction has drawn considerable interest because the C-H o-bond activation and the introduction of some functional group into alkane were achieved in one pot. The similar reaction (Eq. 8) was theoretically investigated with the DFT method [51] ... 

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