Previously held under moratorium from 19 October 2017 until 24 February 2022Directed ruthenium-catalysed C-H functionalisation of heteroarenes, such as 2-phenylpyridine
or 1-phenylpyrazole, has emerged as an efficient and environmentally benign alternative to
traditional cross-coupling chemistry. Using readily available and inexpensive aryl halides, the
mechanisms of these transformations are beginning to be understood. However, there has been
no work completed towards understanding the different directing group power of these
substrates. Many of the literature examples consider only the behaviour of substrates with one
functional group, and the behaviour of more densely functionalised substrates remains
unpredictable.
In this work we have presented a quantitative reactivity scale of directing group power for a
series of ruthenium(II)-catalysed ortho-directed intermolecular C-H arylation reactions across
a range of substrates. The scale of directing group power has been determined using sets of
competition reactions that were analysed by calibrated GC-FID. Using least squares
minimisation, relative reaction rates were obtained for each substrate delivering the first
quantifiable assessment of directing group power.
These results have found that, in our series, 2-phenylpyridine >> 2-phenylpyrazole > Nmethyl-2-phenyl-imidazole > 2-phenyloxazoline >> N-(1-phenylethylidene)aniline. These
results cover a synthetically useful reactivity range of 10²
and allow a quantitative prediction
of site selectivity under the conditions examined.
Additionally, we have presented initial experimental findings that support the intermolecular
quantitative predictions within an intramolecular substrate. This sets the scene for prediction
of regioselectivity in more densely functionalised molecules, on an inter- and intramolecular
setting.Directed ruthenium-catalysed C-H functionalisation of heteroarenes, such as 2-phenylpyridine
or 1-phenylpyrazole, has emerged as an efficient and environmentally benign alternative to
traditional cross-coupling chemistry. Using readily available and inexpensive aryl halides, the
mechanisms of these transformations are beginning to be understood. However, there has been
no work completed towards understanding the different directing group power of these
substrates. Many of the literature examples consider only the behaviour of substrates with one
functional group, and the behaviour of more densely functionalised substrates remains
unpredictable.
In this work we have presented a quantitative reactivity scale of directing group power for a
series of ruthenium(II)-catalysed ortho-directed intermolecular C-H arylation reactions across
a range of substrates. The scale of directing group power has been determined using sets of
competition reactions that were analysed by calibrated GC-FID. Using least squares
minimisation, relative reaction rates were obtained for each substrate delivering the first
quantifiable assessment of directing group power.
These results have found that, in our series, 2-phenylpyridine >> 2-phenylpyrazole > Nmethyl-2-phenyl-imidazole > 2-phenyloxazoline >> N-(1-phenylethylidene)aniline. These
results cover a synthetically useful reactivity range of 10²
and allow a quantitative prediction
of site selectivity under the conditions examined.
Additionally, we have presented initial experimental findings that support the intermolecular
quantitative predictions within an intramolecular substrate. This sets the scene for prediction
of regioselectivity in more densely functionalised molecules, on an inter- and intramolecular
setting
