SCIENCEscience.org 15 APRIL 2022¥VOL 376 ISSUE 6590 277
Fig. 1. Reaction design and development.(A) Merging the benefits of classic
aminations (cyclic secondary amines) and C–H aminations (unactivated olefins)
(middle) inspired the development of a fragment-coupling C–H amination to
furnish complex tertiary amines (this work; bottom middle). The challenges
associated with basic amines in electrophilic metal–mediated catalysis include
undesired Pd(II) coordination that competes with C–H cleavage (bottom left).
Our strategy uses catalyst turnover to regulate the generation of secondary
amine nucleophiles (bottom right). (B) Reaction development and optimization
studies using secondary amine-BF 3 complexes. All reactions were run on a
0.2-mmol scale open to air and moisture. All aminations proceeded in >20:1
linear:branched (L:B) and >20:1E:Zselectivity, and free tertiary amines were
isolated by means of a basic workup followed by column chromatography.
Isolated yields are the average of two experiments. *Dibutyl phosphate.†The
amine-BF 3 was complexed in the reaction vial without purification and was then
subjected to AACC catalysis (supplementary materials).‡Yield was determined
by crude^1 H NMR analysis using benzotrifluoride as an internal standard.RESEARCH | REPORTS