Direct observation of gold/palladium transmetalation in an organogold heck reaction

Article abstract of DOI:10.1021/om2006886

A new Heck-type reaction accessed the migratory insertion chemistry of palladium from organogold complexes. Observation, isolation, and characterization of a palladium intermediate established the role of gold/palladium transmetalation in this reaction. Recent reports of combining the reactivity of organogold compounds with palladium in organic synthesis generally assume a gold-to-palladium transmetalation step, although this step had not been directly observed in these reactions. The results herein furnish experimental evidence for the mechanisms of reactions mediated or catalyzed by both gold and palladium and reveal a migratory insertion strategy for outcompeting homocoupling pathways.

Full text of DOI:10.1021/om2006886

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pubs.acs.org/Organometallics
Direct Observation of Gold/Palladium Transmetalation in an
Organogold Heck Reaction
Katrina E. Roth and Suzanne A. Blum*
Department of Chemistry, University of California, Irvine, California 92697-2025, United States
S Supporting Information
b
ABSTRACT: A new Heck-type reaction accessed the migratory insertion
chemistry of palladium from organogold complexes. Observation, isolation, and
characterization of a palladium intermediate established the role of gold/palla-
dium transmetalation in this reaction. Recent reports of combining the reactivity
of organogold compounds with palladium in organic synthesis generally assume a
gold-to-palladium transmetalation step, although this step had not been directly
observed in these reactions. The results herein furnish experimental evidence for
the mechanisms of reactions mediated or catalyzed by both gold and palladium and reveal a migratory insertion strategy for
outcompeting homocoupling pathways.
he combination of the unique catalytic reactivities of gold1
To explore the viability of this new organogold Heck-type
T
and palladium has recently emerged as a powerful method
reaction, organogold compound 1a, containing a tethered olefin,
was treated with (PPh3)2PdCl2 and then AgOTf in d8-THF at
room temperature (eq 2). Within 10 min the cyclized product 3
was generated in 53% 1H NMR spectroscopic yield. Employment
of AgOTf as an additive was necessary, due to sluggish reactivity
with neutral (PPh3)2PdCl2; the benefits of silver additives
for cationic Heck reactions have been previously reported.8
Addition of excess triethylamine as a base inhibited the compet-
ing protodemetalation9 side reaction and provided 3 in 84%
1H NMR spectroscopic yield. In the absence of palladium, no
formation of product 3 occurred, strongly suggesting that this
reaction proceeded via a gold/palladium transmetalation to form
organopalladium intermediate 2a.10
for functionalizing the intermediate carbonÀgold σ bond gen-
erated during gold-catalyzed substrate rearrangements.2À7 In this
manner, the carbonÀgold bond can be transformed into a new
carbonÀcarbon or carbonÀtin bond that is not available through
gold catalysis alone. The intermediacy of organopalladium com-
plexes in these catalytic processes has yet to be determined
experimentally.3,4 Herein, we not only report a new gold- and
palladium-mediated Heck-type reaction but also provide the
direct observation, isolation, characterization, and reactivity
studies of an intermediate arylpalladium species in this reaction.
This observation lends credence to the proposal that gold(I)-to-
palladium(II) transmetalation reactions operate within the multi-
ple recently reported mono- and dual-catalytic reactions, even in
the absence of single-electron-transfer redox pathways.4d,5 The
reactivity of this isolable arylpalladium intermediate revealed
strategies for the development of new reactions that outcompete
homocoupling pathways.
We envisioned that organogold chemistry could be linked
to the olefin migratory-insertion chemistry of palladium (i.e., a
Heck-type reaction) in analogy to the recent linkings2 of organo-
gold chemistry with palladium-,3,4 nickel-,5 and rhodium-
catalyzed6 and iron-mediated7 cross-coupling with the eventual
goal of dual catalysis (eq 1). Organogold complexes are inert
toward migratory insertion reactions with olefins; however,
migratory insertion reactions are well-established for palladium.
Therefore, we expected that transmetalation of the organic
moiety from gold to palladium would access a migratory inser-
tion reaction unavailable to gold alone.
Within our organogold Heck-type system we reasoned that by
employing a shorter olefin tether we could trap the palladium
species formed after transmetalation. It is known that intramole-
cular 5-endo-trig Heck cyclization reactions are not favored,11À15
and thus the palladium species formed in a short-tethered system
was anticipated to pause after transmetalation and not undergo
subsequent migratory insertion. Indeed, when (o-allylphenyl)-
(triphenylphosphine)gold (1b) was treated with (PPh3)2PdCl2
and AgOTf, the η2-olefin palladium complex 2b was observed by
1H NMR spectroscopy and could be isolated from the crude
reaction mixture for full characterization (eq 3). The structure of
this palladium complex was confirmed by X-ray crystallography
Received: July 26, 2011
Published: August 25, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/om2006886 Organometallics 2011, 30, 4811–4813
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Organometallics
COMMUNICATION
Scheme 1. Proposed Mechanism for the Formation of 4
Figure 1. Palladium intermediate 2b formed via an observable discrete
transmetalation from organogold compound 1b. Thermal ellipsoids are
shown at the 50% probability level; hydrogen atoms and the outer-
sphere solvent of crystallization are removed for clarity.
Scheme 2. Fast Intramolecular Migratory Insertion
Outcompetes Homocoupling
(Figure 1). Observation of this Au/Pd transmetalation provides
the first illustration of this elementary step within the context of
Au/Pd dual-mediated organic reactions and builds upon an earlier
report of a Au/Pd transmetalation by van Koten.16
Due to the shorter tether length, complex 2b did not cyclize
even at 60 °C; however, 2b was a viable intermediate in an
organogold Heck-type reaction with two migratory insertion
events that successively increased the chain length (eq 4).
Treatment of organogold compound 1b with (PPh3)2PdCl2
and then AgOTf and 3-hexyne in one pot produced cyclized
product 4 (49% 1H NMR yield; 6.5 h). This reaction established
that 2b was a viable intermediate for Heck-type reactivity.
known to undergo more kinetically facile ligand transfer;20
thus, the preformed dicationic complex (PPh3)2Pd(OTf)2 may
rapidly undergo transmetalation reactions with two organogold
complexes. Subsequent reductive elimination from the diorga-
nopalladium complex would then yield the homocoupled prod-
uct 8 instead of 2b. In contrast, the active in situ generated
palladium transmetalation partner may be the neutral (PPh3)2-
PdCl2 with chloride abstraction by AgOTf after transmetalation.
However, the precise mechanism leading to this difference in
reagent selectivity is still unclear.
A plausible mechanism for the formation of 4 is shown in
Scheme 1: (i) transmetalation of 1b with palladium to form 2b,
(ii) intermolecular migratory insertion of the alkyne into the
palladiumÀcarbon bond of 2b to form 5,3a,4a (iii) intramolecular
migratory insertion of the unactivated tethered olefin to form 6,17
(iv) β-hydride elimination to form 7,17 and (v) olefin isomeriza-
tion of 7 to yield 4.17,18
The order of addition of reagents provided control over
product selectivity. Ditriflate (PPh3)2Pd(OTf)2 is not the com-
plex responsible for the formation of 2b. When organogold
compound 1b was treated with pregenerated (PPh3)2Pd(OTf)2
in a separate pot, homocoupled product 8 was formed predo-
minantly rather than 2b (eq 5). This result is consistent with
recent findings by Gagnꢀe, in which an attempted Au/Pd catalytic
cross-coupling reaction was thwarted by undesired competing
homocoupling processes.4d,19 Cationic palladium complexes are
A fundamental understanding of the intermediates involved
led to a substrate-control strategy for avoiding homocoupling
that was complementary to the reagent-control method (vide
infra). When organogold compound 1a, with a longer olefin
tether, was treated with preformed (PPh3)2Pd(OTf)2 under
otherwise identical conditions, the migratory insertion pathway
successfully proceeded to yield cyclized 3 as the major product
(Scheme 2). No homocoupled product was generated with this
substrate. Thus, homocoupling was outcompeted by employing a
substrate with a tether length suitable for rapid downstream
intramolecular migratory insertion reactivity.
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COMMUNICATION
In conclusion, we have demonstrated the first gold and
palladium Heck-type reaction. Characterization of an organo-
palladium complex unambiguously established its intermediacy
in the dual-metal reaction. Conditions to outcompete homo-
coupling reactivity between gold and palladium were developed
by reagent and substrate control, demonstrating a successful
migratory insertion strategy for the design of dual-metal reac-
tions with gold and palladium. More broadly, these results
provide key fundamental information for the future develop-
ment of dual-catalytic reactions that combine the substrate
rearrangement power of gold with the unique reactivity of a
second transition metal.
(10) The organogold complex 1a (1.0 equiv) was treated with
AgOTf (2.0 equiv) in d8-THF. No Heck-type product formation was
1
observed by H NMR spectroscopy. No evidence for transmetalation
1
with Ag was observed by H NMR spectroscopy, 31P NMR spectros-
copy, or mass spectrometry.
(11) Ichikawa, J.; Nadano, R.; Ito, N. Chem. Commun. 2006, 4425.
(12) Barluenga, J.; Fernꢀandez, M. A.; Aznar, F.; Valdꢀes, C. Chem. Eur.
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(13) Ackermann, L.; Althammer, A. Synlett 2006, 3125.
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(16) Contel, M.; Stol, M.; Casado, M. A.; van Klink, G. P. M.; Ellis,
D. D.; Spek, A. L.; van Koten, G. Organometallics 2002, 21, 4556.
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’ ASSOCIATED CONTENT
(19) For examples of gold-mediated homocouplings see ref 1a. For
examples of palladium-mediated homocouplings see: Molnꢀar, A. Chem.
Rev. 2011, 111, 2251.
(20) Suzaki, Y.; Yagyu, T.; Osakada, K. J. Organomet. Chem. 2007,
692, 326.
ꢀ
S
Supporting Information. Text and figures giving experi-
b
mental details and compound characterization data and a CIF file
giving crystallographic data for 2b. This material is available free
of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: blums@uci.edu.
’ ACKNOWLEDGMENT
We thank the National Science Foundation for funding
through a CAREER Award for S.A.B. (CHE-0748312) and the
University of CaliforniaÀIrvine for funding. We thank Dr. Joseph
W. Ziller and Mr. Ryan A. Zarkesh for assistance with X-ray
crystallography.
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