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C–H Activation

Alkane borylation reaction kicks metals to the curb

Violet light plus chloride catalyst sets off radical reaction at primary C–H bonds

by Leigh Krietsch Boerner
October 28, 2020 | APPEARED IN VOLUME 98, ISSUE 42

 

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Making carbon–boron bonds is useful in organic synthesis, because chemists can convert those borylated compounds into so many other things. Typically, borylating alkane C–H bonds is tricky, because the reaction favors tertiary and secondary C–H bonds, and to get primary C–H bonds to react, chemists need to add transition metal catalysts. When making pharmaceuticals, scientists eventually have to strip out these toxic metals, which can be an arduous process. Now, Varinder Aggarwal and coworkers at the University of Bristol have found a way to selectively activate primary alkane C–H bonds using light and a chloride-based catalyst (Nature 2020, DOI: 10.1038/s41586-020-2831-6). The group was able to get around 60% yield of clean borylated alkanes under mild conditions.

The researchers trigger the reaction with violet light. First, there is an electron transfer from an oxidant, a N-alkoxyphthalimide ester, to the chloride hydrogen atom transfer catalyst. The resulting species then plucks off the least hindered hydrogen from the target alkane, leaving behind a radical. The radical quickly reacts with a diboron compound to give the borylated alkane product (example shown). The group synthesized over 60 borylated compounds, including alkanes and silanes.

Aggarwal was surprised by the selectivity of the reaction. Hydrogen atom transfer reactions generally target the weakest C–H bonds, meaning tertiary bonds react first. “Our system went the other way,” he says. “Even weak benzylic bonds weren’t borylated.” Through further studies, the group found that the selectivity is largely controlled by steric factors. As the chloride boron complex breaks apart, it grabs the least hindered neighboring H atom, since the bulky boron radical can get closest to it, Aggarwal says.

This reaction proceeds at room temperature for 24 h, and uses a simple light-emitting diode photochemical setup. Similar systems have been scaled up in industry, and are readily accessible to laboratory chemists.

The researchers looked at the problem of alkane borylation from a unique angle, says Cathleen Crudden, an organic chemist from Queen’s University. This new reaction should be highly useful, she says.

UPDATE:

This story was updated on Oct. 29, 2020, to clarify the factors that control the reaction’s selectivity.

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Comments
Shankar (November 3, 2020 11:10 AM)
Wow! I am curious if the authors original intent was to do the reaction as claimed or was an offshoot of serendipity?

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