Organic Letters
Letter
a
erable attention in the transformations of C(sp3)−O bonds
because of their low cost, wide availability, and unique reaction
properties. Under nickel-catalyzed conditions, Hoveyda and
Wang et al. employed PhMgBr or arylzinc chlorides (ArZnCl)
as the nucleophiles to couple with allyl ethers, respectively.12
However, to the best of our knowledge, nickel-catalyzed allyl−
aryl cross-coupling between allylic alkyl ethers and organo-
boron compounds was still unknown.
Scheme 2. Scope of Boronic Acids
Compared with organozinc or Grignard reagents, organo-
boron compounds have emerged as more attractive nucleo-
philic coupling partners because of their advantages, such as
commercial availability, stability to air and moisture, and low
toxicity.13 Herein, we develop a highly efficient protocol for the
direct cross-coupling between allylic alkyl ethers and organo-
boron compounds (Figure 1c). In the presence of an
inexpensive nickel/triphenylphosphine (PPh3) catalytic system
and sodium acetate (NaOAc), a series of coupling products
were generated though C(sp3)−O bond activation and
C(sp3)−C(sp2) bond formation in good to excellent yields.
Initially, 2-(methoxymethyl)-N-methyl-N-(p-tolyl)-
acrylamide (1a) and phenylboronic acid (2a) were chosen as
the model substrates, and a series of experiments aimed at
identifying optimal conditions for selective arylation were
we found that in the presence of bis(1,5-cyclooctadiene)nickel
(Ni(cod)2) (10 mol %), triphenylphosphine (20 mol %), and
sodium acetate (2.0 equiv) the desired product 3aa could be
obtained in 95% yield in 1 mL of toluene at 100 °C (Scheme
1). In addition, under these conditions, by using 2,4,6-
a
b
Isolated yield. (p-OMe-C6H5)3P (20 mol %) was used for 24 h.
c
Reaction performed at 120 °C for 24 h.
bearing dibenzothiophene, carbazole heterocycles, thiophene,
and benzothiophene groups could also be successfully applied
in this process, manufacturing 3an−aq in 53−89% yields.
These results further expanded the scope of boronic acids. The
trans-β-styreneboronic acid 2u also proved to be a suitable
substrate, to afford the desired product 3ar in good yield
(88%).
Next, the broad scope of this protocol with respect to
various allylic ethers was observed (Scheme 3). By employing
a
Scheme 3. Scope of Allylic Ethers
a
Scheme 1. Optimized Conditions and Scope of
Organoboron Compounds
a
b
Isolated yield. GC yield with adamantane as the internal standard.
c
(p-OMe-C6H5)3P (20 mol %) was used instead of PPh3 for 24 h.
d
Reaction performed at 120 °C for 24 h.
triphenylboroxin 4 and phenylboronic acid esters 5 and 6
instead of 2a, the product 3aa could also be generated in high
isolated yields (65−88%).
With the optimized conditions in hand, the substrate scope
of boronic acids was explored (Scheme 2). Both electron-rich
and electron-poor arylboronic acids could react with 1a to
afford the corresponding products 3aa−ak in good to excellent
yields with excellent regioselectivities (60−99%). A wide range
of functional groups, such as methyl (3ab−ad), methoxyl
(3ae), fluoro (3af and 3aj), chloro (3ag), trifluoromethyl
(3ah), trifluoromethoxyl (3ai), and even acetal (3ak), were all
well tolerated. Notably, the steric hindrance did not affect the
high efficiency of this method, and p-, m-, and o-tolylboronic
acids were converted to their desired products with
comparable reactivities (3ab−ad, 77−99% yields). Both 2-
and 1-naphthylboronic acids could serve as the nucleophiles to
give the corresponding 3al and 3am in 93% and 61% yield,
respectively. Furthermore, some (hetero)arylboronic acids
a
b
Isolated yield. (p-OMe-C6H5)3P (20 mol %) was used for 24 h.
c
Reaction was carried out at the 1 mmol scale.
arylboronic acid 2a as the nucleophilic coupling partner,
acrylamide substrate 1b with an unprotected N-H group was
efficiently transformed into the desired product 3ba in 85%
yield. Notably, a series of 2-(methoxymethyl)acrylamides with
alkyl and aryl groups located at the nitrogen core could be
readily applied in this reaction, generating the corresponding
products 3ca−ga in good to excellent yields (77−92%). In
addition, the substrate scope toward heterocyclic unsaturated
B
Org. Lett. XXXX, XXX, XXX−XXX