10.1002/chem.201703746
Chemistry - A European Journal
COMMUNICATION
Miyaura borylation[23] gave the pinacol boronate 48 that
could be functionalized to further increase molecular diversity of
the scaffold. Hydrolysis of boronate 48 under standard
conditions (H2O2/NaOH) provided the phenol 62, which was
readily alkylated with methyl iodide to scaffold 63. The
corresponding aniline 64 was prepared utilizing the transition
metal-free conditions developed by Voth et al. using
hydroxylamine-O-sulfonic acid,[24] providing the aniline 64 in 95%
yield. Pinacol boronate 48 can also be readily converted into two
fluorinated scaffolds. Metallation of the pinacol boronate to the
organosilver followed by treatment with Selectfluor® yielded the
aryl fluoride 65 in 69% yield.[25] Trifluoromethylation was
achieved using the conditions developed by Hartwig using (1,10-
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Experimental Section
For full details of all experiments, and copies of 1H and 13C NMR spectra,
see the Supporting Information.
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We thank the EPSRC (Grant EP/G027919/1) (H.E.B.) and the
University of Nottingham (S.M.N.) for support. A.N.’s contribution
was carried out within the European Lead Factory and has
received support from the Innovative Medicines Initiative Joint
Undertaking under grant agreement n°115489, resources of
which are composed of financial contribution from the European
Union's Seventh Framework Programme (FP7/2007- 2013) and
EFPIA companies’ in-kind contribution. S.M.N. and A.N.
contributed equally.
[19]
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[21]
[22]
Keywords: oxygen heterocycles • nitrogen heterocycles • C–H
[23]
activation • spiro compounds• drug discovery
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