Palladium-catalyzed coupling of allylboronic acids with iodobenzenes. Selective formation of the branched allylic product in the absence of directing groups

Article abstract of DOI:10.1021/ja062585o

Palladium-catalyzed coupling reactions of functionalized allylboronic acids with iodobenzenes were achieved under standard Suzuki-Miyaura coupling conditions. The coupling reactions afforded selectively the branched allylic products in high to excellent y

Full text of DOI:10.1021/ja062585o

Published on Web 06/07/2006
Palladium-Catalyzed Coupling of Allylboronic Acids with Iodobenzenes.
Selective Formation of the Branched Allylic Product in the Absence of
Directing Groups
Sara Sebelius, Vilhelm J. Olsson, Olov A. Wallner, and Ka´lma´n J. Szabo´*
Department of Organic Chemistry, Stockholm UniVersity, SE-106 91 Stockholm, Sweden
Received April 13, 2006; E-mail: kalman@organ.su.se
Table 1. Regioselective Coupling of Allylboronic Acids with Aryl
Palladium-catalyzed allylic substitution has become a widely
applied methodology in organic synthesis.1 A majority of the
palladium-catalyzed nucleophilic allylation reactions proceed via
(η3-allyl)palladium intermediates.1 Therefore, in case of employment
of unsymmetrical allylic precursors, the control of the regioselec-
tivity of the catalytic reactions may be problematic. In particular,
when the reactions proceed through monosubstituted allyl-
palladium intermediates, the nucleophiles preferentially attack the
less hindered allylic terminus, affording the linear allylic product.1f-h
As this product is achiral, there has been a considerable interest to
revert the regioselectivity of this process to obtain the corresponding
branched allylic isomer and thus create the basis for new palladium-
catalyzed asymmetric transformations.2 There have been two main
strategies for conducting the nucleophilic attack toward formation
of the branched allylic isomers: (i) application of directing groups
in the allylic substrate;2a-f or (ii) application of specially designed
ligands to bias the (η3-allyl)palladium intermediates of the reaction.2g-i
Iodidesa
We have now found that the palladium-catalyzed arylation of
functionalized allylboronic acids leads to a selective formation of
the branched allylic isomers without employment of directing
groups or specially designed ligands. Accordingly, under standard
Suzuki-Miyaura coupling conditions,4 allylboronic acids 1a-d
readily undergo palladium(0)-catalyzed substitution reactions with
aryl iodides 2a-d, affording the corresponding terminal alkenes
3a-j (eq 1). The reaction of allylboronic acid 1a with iodobenzene
proceeds smoothly at 40 °C, affording coupling product 3a in 16
h with high yield (entry 1). The application of iodobenzene is
important to obtain a high yield, as coupling of bromobenzene or
phenyltriflate (in place of 2a) with 1a results in only trace amounts
of 3a under the applied mild conditions. Para-substituted iodo-
benzenes reacted similarly to 2a (entries 2 and 3), indicating that
the electronic effects of the aryl substituents have no significant
effect on the outcome of the coupling reaction. Exchange of the
carbethoxy substituents in 4a to bulky phenyl sulfonyl groups (4b)
did not affect the regioselectivity of the reaction (entries 4 and 5).
Furthermore, allylboronic acids with an alkyl (1c) and benzyloxy
group (1d) reacted readily with the same selectivity as 1a and 1b
a The coupling reactions of 1 and 2 were conducted in the presence of
Cs2CO3 and Pd(PPh3)4 (5 mol %) in a mixture of THF and water for 16 h
at 40 °C. b The allylboronic acids were prepared according to refs 3a,b (see
also Supporting Information). c Isolated yield.
(entries 6-10) even when nitrobenzene derivative 2d was employed
as the coupling component (entries 7 and 10).
Because of the mild reaction conditions (40 °C), the catalytic
transformations proceed with high functional group tolerance as
carbethoxy, phenylsulfonyl, aromatic chloro, and nitro groups
remained unchanged under the catalytic transformations. Allylation
of ortho-chloroiodobenzene with 1a was also attempted (cf. entry
2). However, this reaction gave only traces of the ortho-chloro
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C O M M U N I C A T I O N S
analogue of 3b, indicating that the coupling reaction is probably
sensitive to the ortho substitution of the iodobenzene component.
The allylboronic acid precursors can easily be obtained3a,b by
boronation reaction of vinyl cyclopropanes3a (such as 4a,b) and
allyl alcohols3b (such as 5a,b) with diboronic acid (6) in the presence
of catalytic amounts of pincer complex 7.3c Although, allylboronic
acids are remarkably stable3a,b,5a in the presence of water, air, weak
bases, and acids, they rapidly decompose under solvent-free
conditions.3a,b,5b Nevertheless, we have found that allylboronic acids
1a-d can be sufficiently purified by ether extraction of the water-
diluted reaction mixture of the boronation process. The allylboronic
acids are stable in ether and other solvents unless their solution is
evaporated to dryness. Thus, the coupling reactions were carried
out by addition of the corresponding iodoarenes (2a-d), Pd(PPh3)4,
Cs2CO3, and THF to the wet etheral extract of 1a-d followed by
reduction of the solvent volumes. A successful coupling reaction
of 1 and 2 requires the use of Pd(PPh3)4, while pincer complex 7
proved to be inefficient to catalyze the coupling process.
The employed allylboronic acids do not contain any known2
directing groups, and the employed catalyst, Pd(PPh3)4, is one of
the most commonly used palladium(0) sources, in which the PPh3
ligands are not expected to affect the regioselectivity. Nevertheless,
the catalytic allylation process affords selectively the branched
allylic product. To study a possible directing effect of the carbethoxy
group in 1a, we carried out a classical allylic substitution reaction
of 4a with phenyl boronic acid in the presence of Pd2(dba)3 as
catalyst.6a This process provided predominantly the linear product
9 and only traces6b of the branched allylic isomer 3a (eq 2). This
regioselectivity is typical for the classical nucleophilic substitution
of 4a proceeding via (η3-allyl)palladium intermediate.7a On the other
hand, when 4a was converted first to allylboronic acid 1a and then
coupled with iodobenzene (2a), the regiochemistry of the process
is reverted, providing solely the branched product 3a (entry 1, eq
2). Accordingly, the regioselectivity of the coupling reaction of 4a
can be fully controlled by the appropriate choice of the reaction
partners. Furthermore, the above results (eq 2) clearly indicate that
the carbethoxy groups lack any directing effects for the formation
of the branched allylic isomer 3a. Obviously, the alkyl group of
1c also lacks the directing effect on the regioselection of the
arylation reaction (entries 6 and 7). Furthermore, the polar benzyl-
oxy group in 1d is expected to direct the nucleophilic attack to the
less substituted allylic terminus if (η3-allyl)palladium intermediates
were involved in the catalytic process.1g,h Hence, the reaction
proceeds with an excellent regioselectivity, providing the branched
product. All these findings suggest that the above-described
coupling of allylboronic acids 1a-d and aryl iodides 2a-d does
not proceed via (η3-allyl)palladium intermediates.
temperature and 25 h reaction time. In this reaction, several isomeric
products were formed, suggesting that the reaction is initiated by
oxidative addition of 2a to the palladium(0) catalyst followed by
carbopalladation of the allyl boronate and subsequent elimination
of the palladium boronate.7b We believe that a similar mechanism
applies for the palladium-catalyzed coupling of functionalized
allylboronic acids with iodobenzenes (eq 1), as well. This mech-
anism would also explain the selective coupling of 1a-d with 2a-d
(eq 1) involving a highly regioselective carbopalladation process
followed by â-boronate elimination by palladium (eq 3).
In summary, we have shown that the palladium-catalyzed
coupling of allylboronic acids with aryl iodides can be achieved
under standard Suzuki-Miyaura coupling conditions. The reactions
proceed with a remarkably high regioselectivity, providing the
branched allylic isomers. In contrast to palladium-catalyzed nu-
cleophilic substitution reactions proceeding via (η3-allyl)palladium
intermediates, this process does not require directing groups in the
allyl moiety to achieve substitution at the substituted allylic
terminus. As the coupling reaction of allyl boronic acids with
iodobenzenes generates a new stereogenic carbon, the presented
method creates the basis for development of new asymmetric
allylation processes.
Acknowledgment. This work was supported by the Swedish
Research Council (VR).
Supporting Information Available: Experimental procedures as
well as characterization and NMR spectra of the products. This material
is available free of charge via Internet at http://pubs.acs.org.
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A similar mechanistic conclusion was reported by Hallberg and
Nilsson7b studying the palladium-catalyzed coupling reaction of the
parent allylpinacolborane with iodobenzene 2a. Allylpinacolborane
is apparently less reactive than allylboronic acid derivatives since
the reaction required harsh conditions, typically 100 °C reaction
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