Borylative C-H functionalization

Heteroalkenes, with iron, 6, 132 Heteroannulation, allylic benzylamines, 10, 156 Heteroarene chromium carbonyls, preparation and characteristics, 5, 260 Heteroarenes borylation, 10, 242 C—H functionalizations, 10, 127 as metal vapor synthesis milestone, 1, 237 with titanium, 4, 246 vanadium complexes, 5, 48 7]6-Heteroarenes, with platinum, 8, 664 Heteroaromatic compounds... 

They found that combination of the Ir(T) catalyzed C-H borylation and Suzuki coupling sequence led to a two-step, one-pot C-H Suzuki arylation that enabled direct transformation of the N-Boc pyrrole to the C3 arylated intermediate in 78% yield. Following installation of the required acyl group, an application of their oxidative Pd-catalyzed C-H alkenylation reaction enabled formation of the key structural architecture of the natural deliver the natural product. The orthogonal selectivity characteristics displayed by these C-H functionalization processes makes possible iterative functionalization of the heteroaromatic pyrrole core. Utilization of the highly versatile C-H borylation - Suzuki coupling to install the aromatic functionality opens up possibilities of facile analogue synthesis via this route. 

The functionalization of benzylic or arene C-H bonds with boranes leads to synthetically useful boranates. Shimada and co-workers showed that [RhCl(P/Pr3)2(N2)] is an effective catalyst precursor for the borylation of aromatic and benzylic C-H bonds with the use of pinacolborane, resulting in high selectivity for benzylic C-H functionalization. ... 

In terms of atom-economy a very attractive strategy for accessing arylboronic acids is the direct boronylation of arenes through a transition metal promoted C-H functionalization. In addition to the catalyst, a suitable boron donor is required, and both diboronyl esters and dialkoxyboranes are very appropriate in this role. The concept of this type of direct borylation was first demonstrated on alkanes using photochemical... 

Notably, Rh catalysts have also been employed by Hartwig for efficient C—H borylations, which enable even C—H functionalizations of aliphatic C—H bonds in alkanes (42)." "" C—H borylations of alkanes are remarkably selective for functionalization at primary C—H bonds. 

Borylation of the benzylic position of arenes via C—H functionalization has been achieved. Yu has also reported the ability construct C-B bonds via directed C—H functionalization of arylbenzamides catalyzed by Pd(II). Formation of carbon-carbon bonds between arenes and alkyltrifluoroborates, alkylstannanes, and alkyl halides has been reported. The incorporation of amino acid derived... 

A classic example of C-H functionalization is the familiar NBS bromination of a benzyUc site. Recent npdates of this approach allow for direct alkoxylation J. Am. Chem. Soc. 2008, 130, 7824) and net animation (Organic Lett. 2008,10, 1863). For the amination of simple aliphatic H s, Holger F. Bettinger of Ruhr-Universitat Bochum developed (Angew. Chem. Int. Ed. 2008, 47, 4744) the boryl azide 2. The insertion with 1 proceeded to give a statistical mixture of the nitrene insertion products 3 and 4. The tethered C-H functionalization devised (J. Am. Chem. Soc. 2008,130, 7247) by Phil S. Baran of Scripps-La Jolla is selective, as in the conversion to 5 to 6, but appears to be limited to tertiary and benzyUc C-H sites. 

C-H functionalization of arenes is of increasing importance. John F. Hartwig of the University of Illinois has described (Organic Lett. 2007, P, 757 761) improved conditions for Ir-catalyzed meta borylation, and conditions for further coupling of the initial borate 16... 

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. 

The regiospecific functionalization of the terminal alkyl group of simple amines or ethers with bis(pinacolato)-diborane leads to organoboranes. The latter have manifold applications in organic synthesis since the catalytic borylation process can be combined with a functional group transformation step, including Suzuki-Miyaura couplings, for the synthesis of elaborated molecules. Curiously, functionalization of the C-H atoms a to the heteroatom was not observed (Equation (22)). a... 

Functional group tolerance of the borylation is quite high. The reaction occurs selectively at the C-H bond for 1 bearing MeO, Me, I, Br, Cl, F3C, Me02C, and NC groups (Scheme 2) [4—10], In particular, it is interesting to note that aromatic C-H bonds are selectively borylated even in the presence of weaker benzylic C-H bonds or C-halogen bonds. 

Most current regioselective, catalytic functionalization of saturated C-H bonds [1-5] occurs by directed processes [6-13]. In these processes the catalyst or reagent docks at a functional group or reacts at C-H bonds that are located a to a heteroat-om, because these bonds are weaker than more distal ones [14]. Borylation of methyl C-H bonds complements the directed chemistry because it occurs at unactivated C-H bonds with regioselectivity that is independent of the position of the functional group in the reagent [15]. 

The reaction of HBpin in toluene in the presence of RhCl P(/-Pr)3 2(N2) (1 mol%) at 140 °C resulted in a mixture of (borylmethyl)benzene (69%) and bis(boryl)methyl benzene (7%), along with several products arising from aromatic C-H borylation (ca. 15%).345 Rhodium-bpy complexes catalyzed the borylation at the benzylic C-H bond.351 Pd/C was found to be a unique catalyst for selective benzylic C-H borylation of alkylbenzenes by B2pin2 or HBpin (Equation (70)).360 Toluene, xylenes, and mesitylene were all viable substrates however, the reaction can be strongly retarded by the presence of heteroatom functionalities such as MeO and F. Ethylbenzene resulted in a 3 1 mixture of pinacol 1-phenylethylboron and 2-phenylethylboron derivatives. 

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