Borylation feast

I have always found boron chemistry exciting. Maybe the result of too many Suzuki reactions (and reactivity issues) from a previous life in the pharma world. With the recent advances of catalytic borylations, boron is quickly becoming a very versatile element to build on and not any longer just for cross coupling methodologies.

With the advent of C-H activation for C-C bond formation, the scope has expanded to other metal catalysed C-H functionalisations, including C-H borylation under a variety of iridium and rhodium catalysed conditions.

A case in point are 2 recent communications published in JACS.

The first from Tobisu et al (J. Am. Chem. Soc., 2012, 134 (1), pp 115–118) looks at the rhodium catalysed borylation of nitriles through the cleavage of the carbon-nitrile bond (scheme 1).

Scheme 1

According to the author, this is the first example of a rhodium catalysed C-CN bond cleavage other than Ni(0) or silyl metal complex. After an extensive screening of various bases and ligands, a range of boronate esters were obtained in reasonable to excellent yields and excellent compatibility with a range of functionalities (Table 1). Worth noting is the reaction tolerance to esters, amino acids and amines.


Table 1. Rh-catalysed borylation of nitrile

Bulky ortho-substituted aryl nitriles proceed efficiently under less bulky phosphine ligands (PPh3 instead of Xantphos in these cases).

Tobisu makes an attempt at a proposed mechanism involving a boryl rhodium intermediate and iminylrhodium isomerisation prior to β-aryl elimination (Scheme 2).

 Scheme 2

Overall a very unusual but efficient C-CN bond activation promoted by borylrhodium complex.

The second publication from Yu at the Scripps institute (J. Am. Chem. Soc., 2012, 134 (1), pp 134–13) looks at the Palladium oxidative ortho aryl borylation (Scheme 3).

Scheme 3. Palladium catalysed borylation of N-Arylbenzamides

The conditions are so far fairly specific, relying on a very strong ortho directing group  (4-CF3)C6F4, modified dba ligand and a strong oxidant (K2S2O8). After extensive screening conditions, Yu demonstrates some efficient ortho borylation obtained in good yield (Scheme 4).

Scheme 4

At this stage, the aryl substituents are limited but it will be interesting to see if future improvements of this methodology allow for a more diverse range of functionalities.

Both these methodologies are a great addition to the now very versatile and sterically controlled Ir catalysed C-H borylation conditions. The example from Keith James et al (Pfizer & Scripps; Org. Letters, 2010, 12 (17), 3870-3873) is just an illustration of how powerful this methodology has become (Scheme 5)

Scheme 5. Steric Ir catalysed CH borylation

The conclusion from Yu’s communication (Scheme 6) is just a reminder of how versatile C-H borylated compounds have become in accessing new chemical space often difficult to reach via more traditional chemistry methods.

Scheme 6