Organic Letters
Letter
a
stituents at the ortho position led to the formation of alkene
carboacylation products 4l and 4n in 49% and 38% yields,
respectively.
Scheme 3. Scope of Tetraarylborates and Alkenes 4u−4ac
This alkene carboacylation is not limited to simple
monosubstituted benzoate esters. The reaction encompasses
polysubstituted aromatic esters, α,β-unsaturated esters, hetero-
aromatic esters, and aliphatic esters. The reactions of a 3,4-
(MeO)2-substituted benzoate ester and a naphthoate ester
formed products 4o and 4p in 88% yields. A cinnamyl ester
formed the corresponding carboacylation product 4q in 67%
yield, while the reaction of a heteroaromatic ester led to
formation of 4r in 42% yield. However, reactions with
pyridine- and indole-derived esters did not lead to the
formation of the corresponding alkene carboacylation prod-
ucts. In addition, aliphatic esters led to the formation of alkene
carboacylation products 4s and 4t in moderate to good yields
(42−71%). Products of decarbonylative coupling or reductive
decarbonylation were not observed in these alkene carboacy-
lation reactions.
In the course of our studies, we found that the addition of
catalytic BPh3 to the reaction mixture improved the
reproducibility of the catalytic reactions and allowed us to
lower the alkene load in the reaction. For example, reactions of
benzoate esters, a naphthoate ester, and an aliphatic ester have
similar or higher yields when they are conducted in the
presence of 20 mol % BPh3 and 3 equiv of norbornene
(Scheme 2, compounds 4a, 4f, 4p, and 4t). The parent
reaction occurs on a 1.0 mmol scale to form ketone 4a in 75%
yield (eq 1).
a
Ester 1a (0.10 mmol), [Pd(allyl)Cl]2 (0.005 mmol), dppp (0.01
mmol), alkenes 2a−2h (1 mmol), NaBAr4 (0.20 mmol), 1,4-dioxane
(0.30 mL), 110 °C, 16 h, then 1 equiv of DBU added to the crude
reaction mixture, stirred for 30 min at 110 °C, and filtered through
silica. Yields of 4u−4ac are isolated yields after column chromatog-
b
raphy. Reaction run with 20 mol % BPh3 and 3 equiv of alkene.
c
Reaction run for 24 h.
tetraphenylborate 3a generated ketone products 4x−4z in
78−97% yields. Reactions of norbornenes containing ether and
ester substituents formed products 4aa−4ac in 47−53% yields.
Epimerization of the stereocenter at C2 led to isolation of
ketone 4ac as a 1:1.2 mixture of diastereomers. Unfortunately,
reactions of alkenes such as styrene, simple cycloalkenes, and
vinyltrimethylsilane did not lead to the formation of alkene
carboacylation products in appreciable yields.
We propose the catalytic cycle shown in Scheme 4 as a
plausible reaction pathway. Oxidative addition of the active
Pd(0) catalyst to the ester C−O bond of 1a affords acyl−
Pd(II)−alkoxide intermediate I. Migratory insertion of
norbornene into the Pd−(C)acyl bond of intermediate I
generates alkyl−Pd(II) intermediate II. Transmetalation with
sodium tetraphenylborate forms alkyl−Pd(II)−aryl intermedi-
ate III, sodium pentafluorophenoxide, and triphenylborane.
Reductive elimination of the alkyl and aryl ligands from
intermediate III leads to carboacylation product cis-4a and
regenerates the Pd(0) catalyst. Ketone cis-4a can be
epimerized to trans-4a in the presence of sodium penta-
fluorophenoxide and triphenylborane. However, a second
mechanistic pathway can be used to generate 4a. Base-assisted
β-hydride elimination of intermediate II could form enone 5.
Subsequently, 1,4-addition of an organoboron nucleophile to
enone 5 would generate 4a.
We then sought to establish the scope of the alkene
carboacylation with respect to arylboronate nucleophiles in
reactions of norbornene and pentafluorophenyl benzoate 1a
(Scheme 3). The reaction of sodium tetrakis(4-tolylphenyl)-
borate with ester 1a formed carboacylation product 4u in 72%
yield. However, perturbation of the electronic nature of the
parent sodium tetraphenylborate significantly impacted prod-
uct yields. The reactions of sodium tetrakis(4-methoxyphenyl)-
borate and sodium tetrakis(3-methoxyphenyl)borate generated
carboacylation products 4v and 4w in 48% and 10% yields,
respectively. Tetraarylborates containing electron-deficient aryl
groups, such as sodium tetrakis(4-trifluoromethylphenyl)-
borate and sodium tetrakis(4-fluorophenyl)borate, led to
only trace yields of the carboacylation products. These
observations suggest that the efficiency of the catalytic alkene
carboacylation reaction is correlated with the rate of trans-
metalation of the arylboron nucleophile.
We then evaluated palladium-catalyzed carboacylation of a
range of bicyclic alkenes with pentafluorophenyl benzoate 1a
and sodium tetraphenylborate. In the absence of triphenylbor-
ane, palladium-catalyzed carboacylation of additional alkenes
does not occur in >5% yield. However, the addition of 20 mol
% triphenylborane led to formation of the alkene carboacyla-
tion products in modest to good yields and enabled the load of
the alkene substrate to be decreased. Carboacylations of
benzonorbornadienes 2b−2d with ester 1a and sodium
We have obtained data that suggest a Heck reaction/1,4-
addition sequence to generate ketone 4a is feasible under our
reaction conditions. The Pd-catalyzed carboacylation of
norbornene with pentafluorophenyl benzoate and sodium
3509
Org. Lett. 2021, 23, 3507−3512