Nickel-catalyzed cross-coupling of organogold reagents

Article abstract of DOI:10.1021/om200060x

Organogold compounds undergo nickel-catalyzed cross-coupling reactions with aryl and vinyl bromides in high yield under mild conditions. The reaction tolerates both electron-rich and electron-poor organogold complexes, and olefinic bromides undergo cross-coupling with high stereoselectivity. This novel transformation links well-established nickel catalysis with more recent developments in organogold transformations.

Full text of DOI:10.1021/om200060x

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pubs.acs.org/Organometallics
Nickel-Catalyzed Cross-Coupling of Organogold Reagents
Joshua J. Hirner and Suzanne A. Blum*
Department of Chemistry, University of California, Irvine, California 92697-2025, United States
S Supporting Information
b
ABSTRACT: Organogold compounds undergo nickel-cata-
lyzed cross-coupling reactions with aryl and vinyl bromides in
high yield under mild conditions. The reaction tolerates both
electron-rich and electron-poor organogold complexes, and
olefinic bromides undergo cross-coupling with high stereose-
lectivity. This novel transformation links well-established nickel catalysis with more recent developments in organogold
transformations.
he field of homogeneous gold catalysis has experienced a
branching at the R carbon, while the comparatively slow forma-
tion of 4j versus 4a-d suggests that the organogold hybridization
plays a role in the transmetalation rate. Consistent with this
hybridization dependence, Ph3PAuMe failed to afford a cross-
coupling product with 3a under standard reaction conditions. A
similar dependence has been reported in the protodeauration of
organogold compounds, the rate of which also decreases in the
order of sp2 > sp > sp3.29 The involvement of the π system has
been postulated as the cause of this rate dependence in
protodeauration29 and in the transmetalation of other organo-
metallic reagents to nickel;30 therefore, the diminished reaction
rate of 2j may be due to a reduced kinetic accessibility of the
alkynylgold π system resulting from a lower HOMO versus
arylgold reagents 2a-d.29,31 This similarity to protodeauration
in hybridization dependence suggests that nickel may display
electrophilic character in transmetalation reactions with organo-
gold compounds.
T
rapid growth over the past decade.1-4 Despite the versatility
of these reactions, the catalyst-regenerating step often relies upon
carbene insertion5-7 or the trapping of the gold-carbon bond
with an electrophile, such as a proton,1-3,8 carbocation,9,10 or
silicon11 or sulfonyl12 cation equivalent. The interception of
organogold compounds by a second transition metal, however,
would allow for more synthetically diverse transformations. Our
group has demonstrated the palladium-catalyzed addition of
organogold reagents across alkynes and the palladium-catalyzed
cross-coupling of organogold reagents,13 as well as a palladium/
gold dual-catalyzed rearrangement and cross-coupling reaction.14
Palladium-catalyzed coupling reactions stoichiometric in gold
have since been studied more generally,15-20 highlighting the
potentially broad applicability of reactions involving gold and
another transition metal. The compatibility of organogold(I)
complexes with single-electron-reducing transition metals under
catalytic conditions is not well-established.21,22
We herein report a transmetalation between homogeneous
organogold and nickel complexes21 and its application to an
efficient nickel-catalyzed cross-coupling reaction of organogold
reagents. This cross-coupling reaction outcompetes the potential
reduction of gold(I)23,24 by nickel(I).25 The reaction proceeds at
mild temperatures and is effective with organogold compounds
with a variety of electronic properties, establishing a breadth of
coupling reactions available to organogold compounds by open-
ing the door to nickel catalysis, which can offer reactivity both
parallel to26 and unique from that of palladium.27
During initial experiments to establish standard reaction con-
ditions, NiCl2(PCy3)2 (1) was identified as an optimal nickel
precatalyst. When treated with 5 mol % 1 and an aryl bromide,
electron-rich and electron-poor organogold reagents afforded
cross-coupled products in quantitative conversion28 (Table 1,
entries 4a-d). Heterocycles such as bromopyridine, bromopyr-
azine, and bromofurfural are equally effective coupling partners
(4f-h). The scope of the transformation is not limited to arylgold
reagents; isopropenyl- and alkynylgold reagents proved to be
suitable cross-coupling partners (4i-j and 4m). The isoprope-
nylgold couplings demonstrate the tolerance of the reaction for
Organogold butenolide rearrangement substrate 2k was iso-
lated by Hammond,32 and derivatives have been implicated as
intermediates in gold-catalyzed rearrangements.14,33,34 When
introduced to our nickel catalyst system, 2k afforded cross-
1
coupled product 4k in 75% yield by H NMR spectroscopy,
demonstrating the ability to functionalize catalytic organogold
intermediates with this nickel-catalyzed cross-coupling reaction.
A stereocontrol study was conducted using 1-bromo-1-pro-
pene (5) as a model vinyl bromide. The reaction of organogold
compound 2a with (E)-5 yielded exclusively the E cross-coupled
product 6 (eq 1), while (Z)-5 was converted predominately to
(Z)-6 (Z:E = 81:19, eq 2). Control experiments to probe the
origin of the incomplete stereospecificity observed with (Z)-5
revealed that neither the product nor the starting material was
subject to a nickel-catalyzed isomerization. Partial loss of stere-
ochemical integrity could have occurred through the formation
of a vinyl radical through bromine atom abstraction by Ni.35 The
predominance of a stereospecific cross-couping confirms that the
primary pathway for oxidative addition by nickel into 5 does not
Received: January 21, 2011
Published: February 23, 2011
r
2011 American Chemical Society
1299
dx.doi.org/10.1021/om200060x Organometallics 2011, 30, 1299–1302
|

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Table 1. Cross-Coupling Substrate Scoped
a Reaction conducted at 45 °C. b Starting from the Z bromide. c Not isolated due to product volatility. d Conditions: 1.30 equiv of organogold, 1.00 equiv
of aryl bromide (30.0 mM), and 5 mol % NiCl2(PCy3)2. Isolated yield (1H NMR yield of small-scale reaction in C6D6 with mesitylene internal standard).
generate a free organic radical,36 which would result in a
thermodynamic mixture of isomers of 6 regardless of the starting
olefin geometry. In contrast, the reactions of ethyl (Z)-3-
bromopropenoate yielded the cross-coupled products (Z)-4l
and (E)-4m in both high yield and stereochemical purity, but
with inversion of configuration for 4m. An alternative mecha-
nism, such as Michael addition-elimination of a nucleophilic
nickel intermediate,37 may explain the stereochemical scrambling
observed with 4m.
despite the potential thermodynamic favorability of a Au(I)/
Ni(I) redox reaction to form Au(0) and Ni(II).24,25,42
Steps 1 and 4 in this mechanism involve a transmetalation
from a homogeneous organogold complex to nickel.21 The
transmetalation step was investigated through a stoichiometric
transfer from an arylgold compound to NiCl2(PCy3)2. Treat-
ment of 1.0 equiv of 1 under the pseudocatalytic conditions of
excess 2a (10.0 equiv) afforded quantitative conversion to
homocoupled product 12 (eq 3).43 Detection of a paramagnetic
coproduct in this reaction by EPR spectroscopy is consistent with
the generation of a nickel(I) complex as proposed in the catalyst-
generating steps 1-3 in Scheme 1.
Having confirmed the viability of the key nickel-gold trans-
metalation step, we sought to gain a deeper understanding of the
electronic effects involved. A series of competition experiments
was performed in order to determine the relative rate of forma-
tion of cross-coupling products 4a, 4c, and 4d. Relative rates were
calculated using the relative abundance of each product as
A proposed catalytic cycle for this reaction is shown in
Scheme 1. Two successive transmetalation reactions between
organogold 2 and nickel precatalyst 1 yield the diorganonickel-
(II) intermediate 7 (step 1), reductive elimination from which is
kinetically disfavored;38 therefore, single-electron oxidation by
gold(I)39 or the organobromide38 could provide a nickel(III)
species, 8, which gives nickel(I) intermediate 9 upon reductive
elimination (steps 2, 3).40 In analogy to nickel-catalyzed cross-
couplings with metals other than gold, transmetalation of
organogold 2 to nickel(I) is expected to precede oxidative
addition into bromide 3.36,41 The resulting nickel(III) inter-
mediate 11 then affords the observed cross-coupled product 4 via
a rapid reductive elimination.40 Notably, once the active nickel
catalyst has been generated (steps 1-3), the absence of further
homocoupling reactivity suggests that the organogold coupling
partner is not reduced23 under these cross-coupling conditions
1
determined by H NMR spectroscopy after completion of the
reaction (Table 2). An excess of both organogold competition
reagents, 2a and 2c or 2a and 2d (3.0 equiv), was employed in
order to minimize variations in concentration throughout the
course of the experiments. The competitive coupling for R =
OMe versus R = H yielded an equimolar mixture of products
(entry 2), and only slight selectivity was observed for the more
electron-rich product with R = OMe versus R = CF3 (entry 3).
This minimal selectivity contrasts with nickel/boron and nickel/
zinc cross-coupling reactions, which depend more significantly
and linearly on σp (F = 0.8444 and F = -1.74,45 respectively).
1300
dx.doi.org/10.1021/om200060x |Organometallics 2011, 30, 1299–1302

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Scheme 1. Proposed Catalytic Cycle
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details and com-
b
pound characterization. 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 a
Graduate Research Fellowship for J.J.H. (NSF-2010105893). We
also thank the University of California-Irvine for funding, Dr.
John Greaves and Ms. Shirin Sorooshian for mass spectrometry
analysis, Mr. David C. Lacy for assistance with EPR spectroscopy,
and Mr. Yili Shi and Ms. Katrina E. Roth for helpful conversations.
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