andC—to outcompete the desired pathway.
Second, even if the C–H amination does take
place ( 24 ), the resulting enamine moiety
would coordinate strongly to the Pd(II) species
through either the nitrogen lone-pair elec-
trons or the electron-richpbond, in contrast
to the analogous reaction with carbon-based
electrophiles. As a result, the extrusion of NBE
(theb-carbon elimination step) would be more
difficult, which could lead to side productD.Therefore, judicious choice of the NBE cocata-
lyst and careful design of the amine reagent
would likely be the key to balance the require-
ments for each elementary step and address
the aforementioned challenges.SCIENCEscience.org 5 NOVEMBER 2021•VOL 374 ISSUE 6568 735
Fig. 1. Carbonyl 1,2-transposition.(A) Known examples of carbonyl 1,2-migration in medicinal chemistry to produce bioactive analogs with enhanced potency.
Boc,tert-butoxycarbonyl. (B) Carbonyl 1,2-transposition as the key strategy in total syntheses of natural products cascarillone and lycoraminone. (C) Multistep
FG manipulation is often required to relocate ketone carbonyl to the adjacent carbon. (D) One- or two-pot ketone 1,2-migration developed here:a-amination and
ipso-reduction of alkenyl triflates through the Pd/NBE catalysis. iPr, isopropyl; OTf, triflate.
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