Heck coupling using a vinyliodo-mida boronate: An efficient and modular access to polyene frameworks

Article abstract of DOI:10.1021/acs.orglett.5b00042

A simple Heck coupling between an alkenyl iodo-boronate and a variety of terminal olefins is disclosed. This method gives access to a wide range of dienic moieties including valuable bis-functionalized dienes. The synthetic potential of the coupling reaction is demonstrated by a short and modular preparation of several tetraenic compounds.

Full text of DOI:10.1021/acs.orglett.5b00042

Letter
pubs.acs.org/OrgLett
Heck Coupling Using a Vinyliodo-MIDA Boronate: An Efficient and
Modular Access to Polyene Frameworks
Johan Cornil,† Pierre-Georges Echeverria,‡ Phannarath Phansavath,‡ Virginie Ratovelomanana-Vidal,‡
Amandine Guerinot,*,† and Janine Cossy*,†
́
†Laboratoire de Chimie Organique, Institute of Chemistry, Biology and Innovation (CBI)-UMR 8231, ESPCI ParisTech, CNRS, , 10
rue Vauquelin 75231 Paris Cedex 05, France
‡Chimie ParisTech, CNRS, Institut de Recherche de Chimie Paris, PSL Research University, 11 rue Pierre et Marie Curie, 75005
Paris, France
S
* Supporting Information
ABSTRACT: A simple Heck coupling between an alkenyl iodo-boronate and a variety of terminal olefins is disclosed. This
method gives access to a wide range of dienic moieties including valuable bis-functionalized dienes. The synthetic potential of the
coupling reaction is demonstrated by a short and modular preparation of several tetraenic compounds.
yriad natural products incorporating a conjugated
polyenic motif have been isolated.1 They generally
coupling involving the protected haloboronic acid 1a and the
reactive methyl acrylate has been reported.9a,c,12 Herein, we
disclose a Pd-catalyzed Heck reaction between the iodoalkenyl
boronate 1b and a broad range of olefins including functionalized
alkenes (Scheme 1). The great potential of this method is
highlighted by the short synthesis of several polyenic units.
M
display attractive properties, and some of them have been used
as drugs, pigments, or fluorescent probes. Thus, the synthesis of
polyenic moieties still represents a significant challenge for
organic chemists. Traditional olefination methods such as the
Wittig,2 the Horner−Wadsworth−Emmons,3 and the Julia4
reactions have been widely applied to the preparation of
conjugated polyenes, but the lack of stereocontrol as well as
troublesome purifications remain a major obstacle to their use in
total synthesis of complex molecules. Metal-catalyzed sp2−sp2
cross-couplings overcome this difficulty, allowing the con-
struction of polyenic fragments in a stereospecific fashion.5
Hence, Suzuki, Negishi, Stille, or Heck cross-couplings recently
emerged as privileged strategies for the assembly of polyene
moieties.6 However, the preparation, the potential toxicity, as
well as the instability of the alkenyl metal reagents prevent these
reactions from becoming the universal method for the
stereoselective construction of polyenes. Burke et al. partly
solved this problem by focusing on N-methyliminoacetic acid
(MIDA) boronates which have several advantages over boronic
acids or other surrogates: they are bench-stable, compatible with
silica gel chromatography, crystalline, inert toward a range of
reaction conditions, and in addition, easy to cleave.7,8 Thus, bis-
functionalized alkenyl building-blocks incorporating both an
halide atom (I, Br) and a MIDA boronate have been synthesized
and successfully involved in several Pd-catalyzed cross-couplings
including Suzuki, Stille, or Negishi reactions, allowing the
modular synthesis of a large variety of polyenic natural
products.9,10 However, the preparation of alkenyl metal reagents
is still necessary to perform such cross-couplings, and the Heck
reaction, which requires simple olefins, could appear as a very
attractive alternative.11 Surprisingly, only one example of Heck
Scheme 1. Heck Reaction with Halogenoalkenyl Boronates
We first tried to generalize the reported Burke et al. conditions
[Pd(OAc)2, PPh3, and Et3N] for the Heck coupling between 1a
and several alkenes (Scheme 2). However, when the bromo
boronate 1a was treated with N-tosylallylamine, no reaction
Scheme 2. Limitations of the Heck Coupling under Burke et
al.’s Reported Conditions
Received: January 6, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b00042
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Letter
occurred. In addition, when vinylpinacolborane was used as the
olefinic partner, a complex mixture of products was formed.
In order to overcome these limitations, we switched to the
more reactive iodoboronate 1b, and after the reaction conditions
were tuned, Pd(OAc)2 (5 mol %) and AgOAc (1.5 equiv) were
found to afford the coupling products with both ethyl acrylate
and N-tosylallylamine in good yields (76% and 71%,
respectively) in a regioselective fashion (100:0 and 93:7 linear/
branched ratio) (Scheme 3).13
the protection of the hydroxyl group as a silyl ether proved to be
beneficial (Table 1, entries 2−4). In all cases, a satisfactory
regioselectivity of about 90:10 in favor of the linear isomer was
observed. An enantiopure alcohol was successfully used to
produce 3g (65% yield, 85% purity) without epimerization of the
stereocenters, thus highlighting the synthetic value of the method
(Table 1, entry 5). Unfortunately, the coupling did not proceed
with disubstituted olefins such as cyclohexenone (Table 1, entry
6). In contrast, a triene was formed when 1b was reacted with
methylpenta-2,4-dienoate 2i (76%) albeit in a 80:10:10 mixture
of isomers (Table 1, entry 7).14 Styrenic partners exhibited good
reactivity under the coupling conditions whatever the electronic
nature of the substituents on the aryl moiety, and the expected
products were isolated in good yields and high regioselectivities
(Table 1, entries 8 and 9). Interestingly, the presence of
heteroaromatics such as pyridine or indole was not detrimental
to the reaction as 3l and 3m were isolated in good yields (Table 1,
entries 10 and 11).
Scheme 3. Heck Coupling Involving Iodoboronate 1b
These promising results prompted us to examine the reactivity
of functionalized alkene partners in order to access bifunctional
dienes which are highly valuable building blocks in polyene
synthesis.15,16 Bis-functionalized Si−B dienes 5a and 5b were
efficiently prepared from iodo-boronate 1b (60% and 89% yield,
respectively) (Table 2, entries 1 and 2). Vinyl and allyl
phosphonates 4c and 4d were reacted with iodoboronate 1b
delivering the bifunctional dienes 5c and 5d in good yields (66%
and 60%, respectively) (Table 2, entries 3 and 4). To the best of
our knowledge, these dienes are unprecedented in the literature
and could be involved subsequent transformations such as metal-
catalyzed cross-couplings or HWE reaction. Gratifyingly, the bis-
borylated diene 5e was formed with an excellent yield of 90%
(Table 2, entry 5). Thus, it is worth noting that this attractive
building block was obtained in a one-step procedure from
commercially available compounds, using a Heck coupling.17,18
With these conditions in hand, the scope and limitations of the
Heck coupling involving iodo boronate 1b were explored.
Pleasingly, the reaction appeared quite general, and several
functional groups such as an acetal were well tolerated when
present in the olefinic partner (Table 1, entry 1). Allyl alcohol
derivatives were also suitable under the reaction conditions, and
Table 1. Scope and Limitations of the Heck Coupling
Table 2. Access to Bifunctionalized Dienes
a
L/B: linear/branched. In some cases, the impurity (I) could not be
identified undoubtedly as the branched isomer.
An iodo desilylation was performed on 5b, thus achieving a
short synthesis of the dienic iodo boronate 6 which could be
involved in an iterative Heck coupling (Scheme 4).19 The
synthetic utility of 5e was well illustrated by performing two
consecutive Suzuki cross-couplings that allowed the efficient and
stereospecific formation of the (E,E,E,Z)-tetraene 8.20
In order to demonstrate the high synthetic potential of the
method, the MIDA boronate 3b was transformed into the
corresponding alkenyl iodide 9, which was then submitted to a
Suzuki cross-coupling with a range of MIDA boronates (Table
a
L/B: linear/branched. In some cases, the impurity (I) could not be
identified undoubtedly as the branched isomer. The isomers were not
b
separable. The yield was calculated on the L/B or L/I mixture.
c
d
Purchased as a 95:5 mixture of (E)/(Z) isomers. Mixture of isomers.
B
DOI: 10.1021/acs.orglett.5b00042
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Scheme 4. Transformations of Dienes 5b and 5e
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and spectral data for all new
compounds are provided. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: amandine.guerinot@espci.fr.
*E-mail: janine.cossy@espci.fr.
Notes
The authors declare no competing financial interest.
3). It is worth noting that these boronate partners were
previously obtained by a Heck coupling. Only a few
combinations among all possible are depicted here showing
that this short sequence of reactions provides an easy and
modular access to a large variety of polyenic frameworks.
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■
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a
1
The isomeric purity was evaluated on the H NMR spectrum after
purification.
During the course of our studies toward the synthesis of the
macrolactam mirabalin, we were interested in the preparation of
tetraene 13 (Scheme 5).21 Starting from the Heck product 3g,
the targeted compound could be prepared in 3 steps with a
satisfying global yield of 46%.22 This straightforward synthesis
advantageously competes with those already reported in the
literature to access the same tetraenic motif.23,24
Scheme 5. Straightforward Synthesis of Tetraene 13
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library of dienic compounds. The stereoselective method gave a
straightforward access to bis-functionalized building blocks,
which could be easily transformed into polyenic frameworks. The
use of simple olefins as the coupling partner makes the reaction
easy-to-run even on highly advanced synthetic intermediates as
no preparation of alkenyl metal is required. As such, this modular
strategy should rapidly enter into the chemist toolbox for the
construction of polyenic natural and non-natural products.
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(24) A 200 mg portion of the tetraenic fragment 13 could be obtained
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D
DOI: 10.1021/acs.orglett.5b00042
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