Palladium Pincer Complex-Catalyzed Trimethyltin Substitution of Functionalized Propargylic Substrates. An Efficient Route to Propargyl- and Allenyl-Stannanes

Article abstract of DOI:10.1021/ja0391715

Palladium pincer complex-catalyzed reaction of functionalized propargyl chloride (and mesylate) derivatives with hexamethylditin gives allenyl- and propargyl-stannane products. This catalytic activity is in sharp contrast with the reactivity of commonly used palladium(0) catalysts inducing addition of hexamethylditin to the triple bond. The product distribution of the pincer complex-catalyzed reaction is controlled by the substituent effects of the propargylic substrate: electron-withdrawing functionalities give mainly allenyl stannane products, while with electron-donating groups the main product is propargyl stannane. The catalytic reaction proceeds under very mild conditions tolerating many functionalities such as OH, OAc, NR₃, and NR₂Ac groups. Our mechanistic studies indicate that the key intermediate of the reaction is a monotrimethylstannane palladium pincer complex. A remarkable feature of the studied catalytic process is that the palladium catalyst does not undergo redox reactions, but its oxidation state is restricted to palladium(II). Since palladium(0) intermediates does not occur in this process, the catalyst is very stable and highly chemoselective. Copyright

Full text of DOI:10.1021/ja0391715

Published on Web 12/24/2003
Palladium Pincer Complex-Catalyzed Trimethyltin Substitution of
Functionalized Propargylic Substrates. An Efficient Route to Propargyl- and
Allenyl-Stannanes
Johan Kjellgren, Henrik Sunde´n, and Ka´lma´n J. Szabo´*
Department of Organic Chemistry, Stockholm UniVersity, SE-106 91 Stockholm, Sweden
Received October 22, 2003; E-mail: kalman@organ.su.se
Table 1. Palladium-Catalyzed Substitution of Propargylic
Palladium-catalyzed addition of hexaalkylditin to triple bonds
is a widely applied, attractive synthetic route for preparation of
difunctionalized olefins.1,2 The usual application of this method
involves oxidative addition of the palladium(0) catalyst to the Sn-
Sn bond generating a bis-stannyl palladium(II) species, which
subsequently adds to the triple bond of the alkyne substrate.2 Our
recent studies directed toward catalytic application of palladium
pincer complexes in organo-stannane chemistry have indicated that
restriction of the oxidation state of palladium to +2 and the
limitation of the accessible coordination sites to a single one alters
the catalytic reactivity of palladium.3 We have now found (eq 1)
that the pincer complex4,5 (1,2)-catalyzed reaction of hexa-
methylditin (3) with propargylic substrates (4) leads to substitution
reaction instead of bis-stannane addition, affording propargyl
stannanes (5a-e) and allenyl stannanes (6a-j).
Substrates with Hexamethylditina
The catalytic reactions were conducted under mild conditions at
rt or at 0 °C using 2.5 mol % catalyst in THF (Table 1). It was
found that propargyl chloride derivatives react quickly with a high
yield. Propargyl mesylate can also be used as a substrate (entry 4);
however, 4b reacts slower than the corresponding chloride analogue
4a. The product distribution of the reaction was highly dependent
on substituent Q. In the presence of electron-supplying function-
alities (4a,b) such as phenyl (entries 1-4) and alkyl groups (entry
5), the main product is propargyl stannane (5a,b). However, in the
case of carbethoxy- (4e) and hydroxymethylene-types of function-
alities (4f-h) the only product is allenyl stannane. The substituent
effects on the regioselectivity of the reaction were studied by
employment of propargylic substrates with various aminomethylene-
type functionalities (4i-k). The morpholino derivative 4i (involving
a trialkyl-substituted nitrogen atom) reacts with poor selectivity,
affording 5c/6h in a 2:3 ratio. However, in the presence of an
electron-withdrawing acetyl (4j) or tosyl (4k) group on the nitrogen
atom, the allenyl selectivity gradually increases (entries 12-13).
Accordingly, electron-withdrawing groups direct the reaction to
formation of allenyl stannane product, while with electron-supplying
groups, the main product is a propargyl stannane. The only
exception seems to be propargyl chloride (4d) lacking an electron-
withdrawing functionality; nevertheless, its catalytic reaction with
3 gave allenyl stannane 6c.
a All reactions were conducted in THF using 2.5 mol % of catalyst at rt
except entries 5 and 8, where 0 °C was employed. b Catalyst. c Reaction
time in hours. d Propargyl/allenyl ratio; a.p. ) only allene product. e Isolated
yield unless otherwise stated. f Product was not isolated because of its
volatility. The yield was determined by NMR spectroscopy. g Mf )
morpholino group.
The functional group tolerance of the reaction is remarkably high,
which can be ascribed to the mild and neutral reaction conditions.
Carbethoxy (4e) and various propargylic functionalities including
an unprotected OH group (4f-k) are tolerated. Furthermore, the
propargylic acetate functionality (4g) does not undergo oxidative
addition, since the oxidation state of catalyst 1a is restricted to
palladium(II) under the catalytic reaction (vide infra), and therefore
undesired oxidative and reductive processes do not take place.
Complex 1a proved to be the most efficient catalyst in the
propargylic substitution reactions. In this NCN-type of pincer
complex,5a palladium is electron-rich because of coordination to
three σ-donor atoms. The high electron-density on palladium seems
to be an important factor for obtaining high catalytic activity. In
complex 2, the electron density on palladium is reduced by the
presence of a nitro group. This complex still catalyzes the
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C O M M U N I C A T I O N S
and thus palladium is kept in +2 oxidation state throughout the
entire transformation. Accordingly, there are two crucial differences
between the presented catalytic substitution reaction (eq 1) and the
palladium(0)-catalyzed addition reaction:1,2 (i) in the pincer complex-
catalyzed processes, only a single trimethyltin group is coordinated
to palladium (1c), which substitutes the propargylic chloride group,
and (ii) application of pincer catalyst 1a involves that a palladium(0)
species does not form in the catalytic cycle, and therefore an initial
oxidative addition to the propargylic chloride9 (mesylate, acetate,
etc.) functionality can be avoided. These features allow a highly
selective novel transformation of functionalized propargyl chlorides.
Figure 1. Formation of 6c in the reaction of 4d and 3 catalyzed by pincer
complexes 1a (b) and 2 (9).
substitution process; however, it shows a remarkably lower activity
than the parent complex 1a (cf. entries 1 and 2). The retarding
effect of the nitro group was also clearly observed by monitoring
the formation of 6c in the reaction of 4d and 3 with catalytic
amounts of 1a or 2 (Figure 1). Replacement of the σ-donor amino
groups in 1a with π-acceptor phosphines (7) leads to a complete
loss of catalytic activity (entry 3). Commonly used catalysts such
as Pd(PPh3)4 and Li2[PdCl4] do not show any catalytic activity under
the applied reaction conditions.
In summary, we have devised a new pincer complex-catalyzed
trimethyl-stannane substitution reaction of propargyl chlorides with
hexamethylditin. The catalytic reaction proceeds under mild condi-
tions tolerating many functional groups such as OH, OAc, COOEt,
NR3, and NR2Ac. The outcome of the reaction can be controlled
by the choice of the functionalities. Reaction of propargylic
substrates with electron-donating groups gives propargyl stannanes,
while substitution of propargyl chlorides with electron-withdrawing
substituents gives allenyl stannanes. Due to the high level of
functional group tolerance and the operational simplicity, this
method provides an easy access to propargyl and allenyl stannanes,
which are useful building blocks in coupling reactions and in natural
product synthesis.10
The mechanism of the catalytic substitution reaction of 4 with
hexamethylditin (3) (eq 1) is obviously different from the addition
reaction catalyzed by palladium(0) catalysts.1,2 To study the
mechanistic details of the transformation we carried out stoichio-
metric reactions with the catalytically active pincer complex and
the substrates. In these studies we employed acetate complex 1b,
in which the counterion dissociates more easily than in 1a. It was
found that complex 1b and propargylic derivative 4a or 4d do not
react at all in THF-d8 at room temperature (eq 2). However, the
NMR spectrum of pincer complex 1b gradually changed in the
presence of hexamethylditin (3). This process was monitored by
NMR spectroscopy at 25 °C using THF-d8 as a solvent.6 In the 1H
NMR spectrum of the reaction, two new peaks appeared at a high
field: a sharp singlet at 0.05 ppm and a broad singlet at 0.5 ppm.
The peak at 0.5 ppm was identified as the 1H methyl resonance of
Me3Sn-OAc. The peaks of the ligand protons have also shifted
somewhat, still reflecting a Cs symmetry, which is characteristic
for the studied pincer complexes. The 119Sn-NMR spectrum of
the reaction was also monitored in regular time intervals. The sharp
singlet of hexamethylditin (3) resonating at -109.0 ppm was slowly
decreased, while about 15 min after starting the reaction, a new
sharp singlet appeared at -0.2 ppm. This new peak did not arise
from Me3Sn-OAc, since it gives a broad singlet 119Sn-resonance
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 the Internet at http://pubs.acs.org.
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1
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38 1c
(2)
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