yields with inexpensivetert-butyl hydro-
peroxide (TBHP) oxidant, ranging from 40 to
61% (2ato2d,2qto2s, and2agto2ai).
Using 1 atm of O 2 as the oxidant, up to 67%
yield of the dehydrogenation products was
obtained with substrates2ato2d,2qto2s,
and2ai(for optimization details, see table S6).
When the reaction was scaled up to 1.0 mmol,
yield was further improved to 71% (2b) by
using 3 atm of O 2.
Although the problem of product inhibition
could be solved by the use of five-membered
chelating ligands such asL8that inhibit ac-
tivation of C(sp^2 )–H bonds, we wondered
whether it might also be possible to intercept
the vinylic C–H palladated intermediate puta-tively generated by vinyl C(sp^2 )–H activation
of enoic acids when six-membered chelating
ligands are used. If successful, this strategy
would realize a tandem process that achieves
double functionalization through sequential
C(sp^3 )–H and then C(sp^2 )–H activation. Because
the subsequent vinyl C–H functionalization step
needs to be compatible with the conditions ofSCIENCEscience.org 3 DECEMBER 2021•VOL 374 ISSUE 6572 1283
Fig 2. Carboxylic acid scope for the dehydrogenation reaction.Reaction
conditions: 1 (0.1 mmol), Pd(OAc) 2 (4 mol %),L8(4.4 mol %), NaOAc (0.5 equiv),
Li 2 CO 3 (2.0 equiv), Ag 2 CO 3 (2.0 equiv), 1,4-dioxane (0.2 ml),tert-amyl alcohol
(0.8 mL), under N 2 at 100°C for 16 hours. See supplementary materials for details.
*2 equiv oftert-butyl hydroperoxide (TBHP) in water were used as the oxidant instead
of Ag 2 CO 3 at 80°C.†1 atm of O 2 was used instead of Ag 2 CO 3 ; BQ (1,4-benzoquinone,
1.0 equiv), CuBr (0.1 equiv), and dimethylformamide (DMF, 0.8 mL) were added;
8 h.‡In a pressurized vessel at a scale of 1.0 mmol, 3 atm of O 2 were used
instead of Ag 2 CO 3 ; 1,4-benzoquinone (BQ, 1.0 equiv), CuBr (0.1 equiv), and DMF
(dimethylformamide, 8.0 mL) were added; 8 h. ¶Benzyl acrylate (2.0 equiv) was
added; 8 h §at 110°C. hexafluoro-2-propanol (HFIP 0.8 mL) was used as cosolvent
instead oftert-amyl alcohol. Bn, benzyl; Et, ethyl; Ph, phenyl;t-Bu,tert-butyl.RESEARCH | REPORTS