Alkynes as stille reaction pseudohalides: Gold- and palladium-cocatalyzed synthesis of tri- and tetra-substituted olefins

Article abstract of DOI:10.1021/ja710648b

A Stille-type reaction that employs alkynes as pseudohalides provides access to the catalytic chemistry of palladium-carbon σ-bonds starting from π-systems. The synthesis of a variety of tri- and tetra-substituted olefins by addition of sp²- an

Full text of DOI:10.1021/ja710648b

Published on Web 01/30/2008
Alkynes as Stille Reaction Pseudohalides: Gold- and Palladium-Cocatalyzed
Synthesis of Tri- and Tetra-Substituted Olefins
Yili Shi, Sonja M. Peterson, Walter W. Haberaecker III, and Suzanne A. Blum*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025
Received November 27, 2007; E-mail: blums@uci.edu
Palladium-catalyzed carbon-carbon cross-coupling reactions are
a staple of modern synthetic chemistry due to the diverse products
accessible and functional groups tolerated by these reactions. While
powerful, these methods require initial oxidative addition into a
carbon-halogen, -oxygen, or -hydrogen covalent (or ionic) bond
1
2
3
4
5
(
e.g., Stille, Heck, Suzuki, Trost-Tsuji, Buchwald-Hartwig,
6
and the ionic Arndtsen modification ). We now report extension
of this chemistry from C-X bonds to C-C π-bonds through the
employment of alkynes in the place of halides in a Stille-type
vinylstannylation reaction. Carbometalation is a time-tested tech-
Figure 1. Proposed Lewis acid activation of alkynes leads to an increase
in backbonding from Pd(0), permitting Pd(II)-C σ-bond reactivity.
1
Table 1. Effect of Catalyst Composition on Product H NMR Yield
7
nique for the synthesis of olefins from alkynes; however, compared
8
to copper, there are few palladium-catalyzed vinylstannylation
reactions.9 One limitation of Shirakawa and Hiyama’s palladium-
catalyzed vinylstannylation reaction is that double-addition products
predominate. Our reaction provides an expedient route to the
,10
1H NMR
entry
Lewis acid
Pd cat.
yield (%)
1
1,12
monoaddition products, yielding tri- and tetra-substituted olefins
1
2
3
4
5
6
7
8
9
PPh3AuCl
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
24
51
33
62
73
0
0
25
0
from alkynes with absolute regioselectivity and high stereoselec-
tivity via a Au(I)/Pd(0) bimetallic catalyst system that combines
PPh3AuCl/AgSbF6 (1:1)
PPh3AuCl/AgSbF6 (1:2)
PPh3AuSbF6‚CH3CN
PPh AuPF
13
the characteristics of two metals to produce unique reactivity.
1
4-16
Pd2(dba)3
We hypothesized that the alkynophilic
Lewis acid Au(I)
3
6
PPh3AuPF6
none
BF3‚(OMe2)
AgSbF6
PhCO2H
PPh3AuCl/AgSbF6 (1:1)
PPh3AuCl/AgSbF6 (1:1)
none
Pd2(dba)3
Pd2(dba)3
would lower the LUMO of an alkyne fragment, promoting
backbonding (i.e., oxidative addition) from Pd(0) into the alkyne,1
which in turn increases palladium-carbon σ-bond character (Figure
7-20
Pd (dba)3
2
1). Andersen reported a conceptually similar, structurally character-
10
Pd2(dba)3
Pd(Pt-Bu3)2
(PPh3)2PdCl2
0
39
trace
1
1
1
2
ized µ-ethylene bimetallic complex with Pt(0) as the Lewis base
17-20
and Yb(II) as the Lewis acid.
To our knowledge, no employ-
ment of this structure class as a catalytic intermediate has been
developed, despite the potential generality of such a method for
accessing late-metal-carbon σ-bonds. With an alkyne as the oxi-
dative addition partner, no C-X bond would be necessary for a
cross-coupling reaction (i.e., the alkyne serves as a pseudohalide).21
In order to explore this hypothesis, dimethyl acetylenedicar-
A probable competing alkyne oligomerization reaction, detected
by H NMR spectroscopy, was circumvented by slow addition of
1
the alkyne. Accordingly, reaction of tri-n-butylvinylstannane with
1
slowly added DMAD produces 1 in 96% H NMR yield, with a
95:5 selectivity for the syn addition product (Table 2, entry 1).
With optimized conditions in hand, we continued to explore the
stereochemistry of the vinylstannylation reaction. Seven of eight
substrates exhibit excellent syn:anti addition selectivities (g95:5;
exception entry 2, 89:11 syn:anti). As expected for a Stille-type
reaction, the addition is stereospecific with respect to the vinyl-
stannane: (Z)-propenyltri-n-butylstannane and (E)-propenyltri-n-
butylstannane couple with preference for retention of configuration.
Some stereochemical leakage to E occurs with the sterically bulky
Z stannane (60:40 Z:E, entry 6).
boxylate (DMAD) was treated with 20 mol % of PPh
and 5 mol % of Pd (dba) in the presence of 1 equiv of
tri-n-butylvinylstannane. Gratifyingly, these conditions produced
3 6
AuCl/AgSbF
2
3
1
22
tetrasubstituted olefin 1a in 51% H NMR yield (Table 1, entry
). Optimization of the Lewis acid catalyst revealed that a weakly
coordinating anion for the gold complex, such as SbF or PF , was
required for high reactivity (entries 1, 2, and 5). Employment of
the less alkynophilic14 Lewis and Brønsted acids AgSbF
, BF , and
2
6
6
6
3
benzoic acid resulted in zero or poor conversion (entries 8-10).
More than 1 equiv of silver inhibited the reaction (entry 3).
Consistent with this inhibitory effect, isolation of the cationic Au-
The utility of the Pd/Au-catalyzed method for formation of tri-
and tetra-substituted olefins is illustrated by a range of stannane
2
(I) catalyst resulted in significantly higher conversion than the
partners (i.e., sp , sp, secondary, oxygenated, â-substituted; Table
24
catalyst generated in situ (entries 2 and 4). The observation of an
inhibitory effect of silver in our reaction is of particular note given
the current interest in developing efficient cationic Au(I) catalysts
via silver salt metathesis.1 Both Au(I) and Pd(0) were required
for conversion (entries 6 and 7). Supporting Pd(0)’s role as an
oxidative addition partner to the alkyne, Pd(II) is significantly less
active (entry 12).
2). Complete regioselectivity is maintained even in the presence
of a sterically bulky tert-butyl ester. Interestingly, no evidence for
reentry into the catalytic cycle by the product vinylstannanes is
observed. Presumably, this is because of the increased steric
hindrance provided by R-branching and â-substitution.
4,23
A proposed mechanism for the Au- and Pd-cocatalyzed vinyl-
stannylation of alkynes is detailed in Scheme 1. Coordination of
2168
9
J. AM. CHEM. SOC. 2008, 130, 2168-2169
10.1021/ja710648b CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Scope of Au- and Pd-Catalyzed Alkyne Stille Reactiona
In conclusion, we have developed a palladium- and gold-
cocatalyzed vinylstannylation of alkynes to form tri- and tetra-
substituted olefins with excellent regio- and stereocontrol. The
reactions are postulated to proceed via Au(I) activation of the
alkynes toward nucleophilic metalation/oxidative addition to
Pd(0). In this mechanism, the alkyne serves as a pseudohalide
in a Stille-type cross-coupling reaction. In a broader sense, the
reactions reported herein provide an entry into the extensive catalytic
chemistry of palladium-carbon σ-bonds starting from π-systems.
We are currently exploring the mechanism of this reaction and
developing additional functionalization reactions of these activated
π-systems. These investigations are part of ongoing research in our
group to explore the use of Lewis acids to activate organic substrates
toward metalation.
Acknowledgment. We thank The Petroleum Research Fund
(46285-G1) and the University of California at Irvine for funding,
and Dr. John Greaves for mass spectrometry assistance.
Supporting Information Available: Experimental procedures and
compound characterization. This material is available free of charge
via the Internet at http://pubs.acs.org.
a
Conditions: CH2Cl2, slow addition of alkyne over 6 h, then 24-48 h,
b
2
4
3 °C, 2.0 equiv of stannane. Exception: entry 2, 89:11 syn:anti. c With
.0 equiv of stannane. A ratio of 60:40 syn Z:syn E was isolated.
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(
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(
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1
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1
b demonstrates synthetic access to the full amount of material
1
9
represented by the H NMR yield.
JA710648B
J. AM. CHEM. SOC.
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VOL. 130, NO. 7, 2008 2169