ARTICLES
suitable N−H oxaziridine aminating agent for both sterically
demanding and less nucleophilic arylmetals.
Conclusion
We have demonstrated that bench-stable N−H and N−alkyl oxazir-
idines derived from inexpensive terpenoid scaffolds can serve as
effective primary aminating and hydroxylating reagents to give
rise directly to primary arylamines and phenols from readily avail-
able arylmetals in the absence of transition-metal catalysts and
under exceedingly mild conditions. This one-step/one-pot method
is expected to become widely used in both academic and industrial
laboratories as it will provide practical and scalable synthetic access
to a vast array of structurally diverse unprotected aromatic amines
and hydroxyarenes to be used as building blocks or as value-
added compounds. Although this approach is a step in the right
direction towards ‘greener’ chemistry, the preparation of the oxazir-
idine reagents needs further improvements to achieve a higher level
of sustainability. Therefore, more-efficient synthetic routes to these
reagents are currently being developed.
For the direct hydroxylation of arylmetals, several N−alkyl
oxaziridines have been prepared and evaluated (Supplementary
Information, pages 7 and 8). N−benzyl oxaziridine 19b was selected
as the optimal reagent given its ease of synthesis, bench stability and
chemoselectivity. The examples in Table 4 amply illustrate the
unprecedented functional group tolerance of this reagent as both
oxidatively (entries 9, 17, 19, 20, 21 and 24, Table 4) and hydrolyti-
cally (entries 22 and 23, Table 4) sensitive functionalities remained
untouched during the hydroxylation process. The phenols them-
selves are usually highly oxidatively sensitive even without
additional electron-donating groups on their aromatic rings1; that
most of the phenol products were isolated in good yield attests to
the unprecedented mildness of this method.
Our hypothesis of low kinetic acidity is based on M06-2X/def2-
TZVP density functional calculations in THF continuum solvent for
the reaction of 18 with (PhMgBr)2 (modelled as dinuclear bridging
and Schlenk-type structures (details are given on page 65 of the
Supplementary Information))44. Consistent with this hypothesis
is that the calculated pKa for 18, assuming MgBr coordination of the
anion in THF solution, is ∼34. Proton transfer between (PhMgBr)2
and 18 is thermodynamically favourable (ΔG = −13.4 kcal mol–1),
and therefore the selective amination versus proton transfer must be
governed by kinetic pathways37.
Received 28 June 2016; accepted 11 October 2016;
published online 28 November 2016
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