Science - USA (2021-12-03)

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 of

SCIENCEscience.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.

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